Editorial Material
Cell Biology
Zhihui Zhang, Guanghou Shui, Min-Dian Li
Summary: Meal timing can reset cellular circadian clocks in the body, with clocks in different tissues being reset to varying degrees by feeding rhythms, and modulated by the central clock and the liver clock. Tissue-specific regulation and intercellular signaling play essential roles in clock synchronization.
TRENDS IN CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Evrim Yildirim, Rachel Curtis, Dae-Sung Hwangbo
Summary: Biological clocks are essential mechanisms that synchronize physiological and behavioral processes with external cues to ensure organisms' fitness and survival. While the central clock in the brain drives daily activity rhythms, peripheral tissues have their own clock systems generating metabolic and physiological rhythms. The fruit fly Drosophila melanogaster has been a widely studied model organism for investigating the mechanism and functions of circadian clocks.
Letter
Plant Sciences
James Ronald, Anthony J. Wilkinson, Seth J. Davis
Summary: The sub-nuclear localization of EARLY FLOWERING3 gene responds to changes in ambient temperature.
Article
Biology
Marieke M. B. Hoekstra, Maxime Jan, Georgia Katsioudi, Yann Emmenegger, Paul Franken
Summary: The study demonstrated a correlation between PER2 bioluminescence and sleep-wake status in peripheral tissues, indicating integration of sleep-wake information by clock gene circuitry. Mathematical modeling revealed a dynamic description of PER2 driven by sleep-wake-dependent and SCN-independent circadian forces.
Article
Neurosciences
Jia Li, Yali Chen, Jin Liu, Donghang Zhang, Peng Liang, Peilin Lu, Jiefei Shen, Changhong Miao, Yunxia Zuo, Cheng Zhou
Summary: Inflammatory pain involves neuronal hyperexcitability and sensitization of nociceptive neurons in the spinal cord, with the sodium leak channel (NALCN) potentially playing a key role in this pathological process. In a rat model of inflammatory pain induced by CFA, increased NALCN expression and activity contributed to enhanced neuronal sensitization, while NALCN knockdown led to reduced excitability and alleviated pain symptoms. These findings suggest that NALCN may be a novel molecular target for the management of inflammatory pain.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Ye Young Kim, Hagoon Jang, Gung Lee, Yong Geun Jeon, Jee Hyung Sohn, Ji Seul Han, Won Taek Lee, Jeu Park, Jin Young Huh, Hahn Nahmgoong, Sang Mun Han, Jeesoo Kim, Minwoo Pak, Sun Kim, Jong-Seo Kim, Jae Bum Kim
Summary: This study demonstrated that the reduction of hepatic CRY1 protein in diabetic mice is stimulated by FBXL3-dependent proteasomal degradation and GSK3 beta-induced CRY1 phosphorylation. Tight regulation of hepatic CRY1 protein stability is crucial for maintaining systemic glucose homeostasis.
Article
Biochemistry & Molecular Biology
Xinyu Zhao, Shu Huang, Peng Zhang, Xue Qiao, Yu Liu, Miren Dong, Qilin Yi, Lingling Wang, Linsheng Song
Summary: This study identified the role of EsCry in regulating the expression of cytokines in Chinese mitten crab, showing that it negatively regulates TNF and IL-16 through inhibiting their transcription factors LITAF and ILF.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Polly Downton, Fabio Sanna, Robert Maidstone, Toryn M. Poolman, Edward A. Hayter, Suzanna H. Dickson, Nick A. Ciccone, James O. Early, Antony Adamson, David G. Spiller, Devin A. Simpkins, Matthew Baxter, Roman Fischer, Magnus Rattray, Andrew S. I. Loudon, Julie E. Gibbs, David A. Bechtold, David W. Ray
Summary: Chronic inflammation is associated with metabolic dysfunction, with a temporal crosstalk between inflammatory and metabolic processes. Research has shown that arthritis drives changes in lipid metabolism and mitochondrial function, leading to the accumulation of bioactive lipid species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Shani Tsameret, Daniela Jakubowicz, Zohar Landau, Julio Wainstein, Tali Ganz, Itamar Raz, Nava Chapnik, Oren Froy
Summary: The study found that soluble factors present in the serum of type 2 diabetes patients consuming a three-meal diet can reset circadian rhythms in the liver, leading to a gene expression pattern similar to that of healthy individuals, which contributes to improved glucose metabolism.
DIABETES RESEARCH AND CLINICAL PRACTICE
(2021)
Review
Physiology
Iwona Olejniczak, Kimberly Begemann, Ines Wilhelm, Henrik Oster
Summary: Circadian clocks play a crucial role in regulating physiology and behavior, particularly in the central reward system. They impact neurotransmitter signaling, neuroendocrine circuits, and sensitivity to external stimuli. Disruption of circadian rhythms can affect reward signaling, leading to the development of behavioral and substance use disorders. This review summarizes current knowledge on the interaction between circadian clocks and reward, highlighting the effects of chronodisruption on reward signaling in animal models. The translation of these findings to human reward (dys-) function and the clinical implications are discussed, along with the challenges and approaches in incorporating circadian medicine concepts into the therapy of substance use disorders.
Article
Neurosciences
Diana J. Goode, Derek C. Molliver
Summary: This study identifies a mechanism for regulating mitochondrial function by Epac2 in DRG sensory neurons, contributing to acute inflammatory hyperalgesia in male mice. Systemic administration of the cyclooxygenase 2 inhibitor celecoxib can suppress Pdha1 phosphorylation in male DRG, thereby alleviating PGE2-induced heat hyperalgesia.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biology
Wen-Zhao Cui, Jian-Feng Qiu, Tai-Ming Dai, Zhuo Chen, Jiang-Lan Li, Kai Liu, Yu-Jun Wang, Yang-Hu Sima, Shi-Qing Xu
Summary: Diapause in insects is a developmental transition regulated by the circadian clock system and endocrine system. This study focused on a mutant silkmoth with the Period gene knocked out, which altered the classic diapause pathway and disrupted the predetermined effects of temperature and photoperiod on diapause determination. The impaired circadian clock system in the mutant resulted in up-regulation of the GABA receptor gene, leading to a cascade effect that ultimately reduced the diapause-inducing effect of diapause hormone.
Article
Biochemistry & Molecular Biology
Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta
Summary: This study provides evidence for the first time that Anaplasma phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. The results suggest that the circadian modulation of tick gene expression plays an important role in arthropod blood feeding and transmission of pathogens from vector to the vertebrate host.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Kangkai Xia, Shujing Li, Yuxi Yang, Xiaoxia Shi, Binggong Zhao, Linlin Lv, Zhiqiang Xin, Jie Kang, Ping Ren, Huijian Wu
Summary: Breast cancer is a global health issue with rising incidence. Disruption of the internal circadian clock, including the genetic dysregulation of Cry2, can contribute to the development of diseases, such as tumors. This study focuses on understanding the post-translational modifications of Cry2 and its role in breast cancer pathogenesis.
CELL DEATH & DISEASE
(2023)
Article
Psychology, Biological
Paola Fernandes, Luciana de Melo Pereira, Nayara Abreu Coelho Horta, Thais Santana Rocha Cardoso, Candido Celso Coimbra, Raphael Escorsim Szawka, Grace Schenatto Pereira, Maristela Oliveira Poletini
Summary: Social interaction can affect SCN activity, particularly in regulating response to environmental light and the formation of body temperature rhythms.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Cell Biology
Salvatore Rizza, Luca Di Leo, Chiara Pecorari, Paola Giglio, Fiorella Faienza, Costanza Montagna, Emiliano Maiani, Michele Puglia, Francesca M. Bosisio, Trine Skov Petersen, Lin Lin, Vendela Rissler, Juan Salamanca Viloria, Yonglun Luo, Elena Papaleo, Daniela De Zio, Blagoy Blagoev, Giuseppe Filomeni
Summary: Nitric oxide (NO) production in the tumor microenvironment contributes to cancer development. This study reveals that S-nitrosylation, a post-translational modification mediated by NO, plays a role in sustaining tumorigenesis. The enzyme GSNOR, which deactivates S-nitrosylation, is found to be hypo-expressed in various human malignancies. GSNOR deficiency leads to S-nitrosylation of focal adhesion kinase 1 (FAK1), enhancing its autophosphorylation and promoting cancer cell survival in suspension. GSNOR-deficient tumor models are highly sensitive to FAK1 inhibitors, suggesting GSNOR as a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Camilla Blunk Brandt, Sofie Vestergaard Fonager, Janos Hasko, Rikke Bek Helmig, Soren Degn, Lars Bolund, Niels Jessen, Lin Lin, Yonglun Luo
Summary: This study reports a highly efficient and selection-free CRISPR gene editing approach using ribonucleoprotein (RNP) complex in primary endothelial cells (HUVECs). The optimized mRNA delivery protocol achieved nearly 100% transfection efficiency of HUVECs with EGFP mRNA. By utilizing this optimized DNA-free approach, highly efficient (98%) and biallelic HIF1A knockout in HUVECs without selection was achieved using three different gRNAs. Functional assays validated the effects of HIF1A knockout on ECs' angiogenic characteristics and response to hypoxia. This work provides a simple method for highly efficient gene editing of primary endothelial cells (HUVECs) in studies and manipulations of ECs functions.
Article
Oncology
Yirong Xiang, Shuai Li, Hongzhi Wang, Maxiaowei Song, Ke Hu, Fengwei Wang, Zhi Wang, Zhiyong Niu, Jin Liu, Yong Cai, Yongheng Li, Xianggao Zhu, Jianhao Geng, Yangzi Zhang, Huajing Teng, Weihu Wang
Summary: A prediction model was developed and validated to predict T downstaging in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy. The model based on multicenter pre-treatment radiomics showed good performance and may facilitate individualized treatment decision-making.
CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
(2023)
Article
Hematology
Anne Bruun Rovsing, Emil Aagaard Thomsen, Ian Nielsen, Thomas Wisbech Skov, Yonglun Luo, Karen Dybkaer, Jacob Giehm Mikkelsen
Summary: Using CRISPR screening, we uncover the cellular response to vincristine in DLBCL, identifying genes related to mitotic spindle organization and the mechanism behind vincristine resistance involving KIF18B and USP28. Our findings provide potential drug targets and mechanisms for future drug regimens.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Bin Liu, Ran Chen, Yidan Zhang, Jinrong Huang, Yonglun Luo, Susanne Rosthoj, Chenyang Zhao, Marja Jaattela
Summary: Commonly used antihistamines and other cationic amphiphilic drugs (CADs) have emerged as potential cancer drugs due to their ability to alter lysosomal pH and inhibit STAT3 signaling, leading to cancer cell apoptosis and inhibition of tumor growth. The rapid elevation of lysosomal pH induced by CADs is caused by lysosomal H+ efflux mediated by P2RX4 and precedes lysosomal membrane permeabilization. These findings highlight the anticancer mechanisms of CADs and support their repurposing as cheap and safe cancer drugs, especially in combination with STAT3 inhibition.
Article
Neurosciences
Hankui Liu, Liping Guan, Min Deng, Lars Bolund, Karsten Kristiansen, Jianguo Zhang, Yonglun Luo, Zhanchi Zhang
Summary: By analyzing the expression of ALS-related genes in different cell types using single-cell transcriptomics data, we found that alpha- and gamma-motor neurons are associated with ALS susceptibility and pathogenicity genes, respectively, indicating differences in biological processes between sporadic and familial ALS.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Xiaoying Zhao, Kunli Qu, Benedetta Curci, Huanming Yang, Lars Bolund, Lin Lin, Yonglun Luo
Summary: Recent progress in CRISPR gene editing tools has expanded the possibilities for treating devastating genetic diseases. In this study, three methods of gene editing (NHBEJ, HDR, and PE) were compared for correcting loss-of-function mutations in Duchenne Muscular Dystrophy. The highest efficiency was achieved with NHBEJ, followed by HDR and PE2. The correction efficiency was increased with the use of PE3. This study demonstrates the potential for highly efficient correction of DMD mutations using CRISPR gene editing.
Article
Biology
Shangchen Yang, Tianming Lan, Rongping Wei, Ling Zhang, Lin Lin, Hanyu Du, Yunting Huang, Guiquan Zhang, Shan Huang, Minhui Shi, Chengdong Wang, Qing Wang, Rengui Li, Lei Han, Dan Tang, Haimeng Li, Hemin Zhang, Jie Cui, Haorong Lu, Jinrong Huang, Yonglun Luo, Desheng Li, Qiu-Hong Wan, Huan Liu, Sheng-Guo Fang
Summary: This study provides insights into the cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas, and helps to understand the physiological adaptation response to low nutrient conditions.
Article
Biochemistry & Molecular Biology
Jiaying Huang, Qiupeng Lin, Hongyuan Fei, Zixin He, Hu Xu, Yunjia Li, Kunli Qu, Peng Han, Qiang Gao, Boshu Li, Guanwen Liu, Lixiao Zhang, Jiacheng Hu, Rui Zhang, Erwei Zuo, Yonglun Luo, Yidong Ran, Jin-Long Qiu, Kevin Tianmeng Zhao, Caixia Gao
Summary: The elucidation of protein function and its exploitation in bioengineering have greatly advanced the life sciences. Protein mining efforts generally rely on amino acid sequences rather than protein structures. We describe here the use of AlphaFold2 to predict and subsequently cluster an entire protein family based on predicted structure similarities. We engineered the smallest single-strand-specific cytidine deaminase, enabling efficient cytosine base editor (CBE) to be packaged into a single adeno-associated virus (AAV). Importantly, we profiled a deaminase from this clade that edits robustly in soybean plants, which previously was inaccessible to CBEs. These discovered deaminases, based on AI-assisted structural predictions, greatly expand the utility of base editors for therapeutic and agricultural applications.
Article
Biochemistry & Molecular Biology
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixo Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
Summary: AMBRA1 is a key factor for nervous system development, primarily associated with autophagy and cell proliferation control. This study reveals that AMBRA1 is phosphorylated during mitosis and is critical for spindle function and orientation, driven by NUMA1 protein. The localization and dynamics of NUMA1 are dependent on AMBRA1 presence, phosphorylation, and binding ability. These findings suggest an additional role of AMBRA1 in tissue morphogenesis and differentiation, which could have implications for development and cancer oncogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Oncology
Signe Neldeborg, Johannes Frasez Soerensen, Charlotte Thornild Moller, Marie Bill, Zongliang Gao, Rasmus O. Bak, Kasper Holm, Boe Sorensen, Mette Nyegaard, Yonglun Luo, Peter Hokland, Magnus Stougaard, Maja Ludvigsen, Christian Kanstrup Holm
Summary: Oncogenic fusion drivers in hematological cancers can be targeted using a new dual intron-targeting CRISPR-Cas9 treatment strategy. This strategy can efficiently disrupt fusion genes without requiring precise knowledge of the breakpoints in t(8;21) AML. In vitro and in vivo experiments showed significant reduction in cell growth and tumor growth in response to disruption of RUNX1-RUNX1T1. These findings were confirmed in primary cells from an AML patient.
Article
Biochemistry & Molecular Biology
Aikaterini Skorda, Anna Rossberg Lauridsen, Chengnan Wu, Jinrong Huang, Monika Mrackova, Nuggi Ingholt Winther, Vanessa Jank, Zsofia Sztupinszki, Robert Strauss, Mesut Bilgin, Kenji Maeda, Bin Liu, Yonglun Luo, Marja Jaattela, Tuula Kallunki
Summary: Cancer cells depend on cholesterol and have mechanisms for controlling its homeostasis. They can switch between cholesterol synthesis and uptake depending on their needs and environmental changes. Through oncogenic growth factor signaling, cancer cells promote the uptake and utilization of extracellular cholesterol, which is facilitated by Myeloid Zinc Finger 1 (MZF1)-mediated Niemann Pick C1 (NPC1) expression and increased macropinocytosis. This process allows cancer cells to obtain cholesterol for their energy-consuming activities, such as invasion.
Article
Multidisciplinary Sciences
Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Ewa Terczynska-Dyla, Kristian Savstrup Kastberg, Emily Yang, Alysa Nicole Rallistan, Quinton Raymond Markett, Gudrun Winther, Sofie Fonager, Lasse F. Voss, Mathias K. Pedersen, Nina van Campen, Alexey Ferapontov, Lisbeth Jensen, Jinrong Huang, John D. Nieland, Cees E. van der Poel, Johan Palmfeldt, Michael C. Carroll, Paul J. Utz, Yonglun Luo, Lin Lin, Soren E. Degn
Summary: Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. A murine model experiment demonstrated that the autoimmune response can be initiated outside of germinal centers. B cells can directly relay autoreactivity between different compartments of MHC-restricted T cells and propagate the autoimmune response.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Jingyu Xiao, Fei Wang, Xiaoyan Hu, Dongli Li, Geng Liu, Qumiao Xu, Chao Chen, Haitao Xiang, Xuan Dong, Linnan Zhu, Dishuang Yang, Yanan Gao, Meijuan Wang, Yonglun Luo, Cheng-Chi Chao, Guanglei Li, Qiongyu Guo
Summary: Researchers used a 3D tumor model based on recellularized liver matrix to investigate T-cell immune response to HCC neoantigens. They collected whole exome sequencing data of 364 HCC patients and predicted 25 highly potential immunogenic neoantigens in silico. Six of the HCC neoantigen candidates were functionally validated and their minigenes were constructed. The 3D RLM HCC tumor model showed a specific immune response to the minigene-modified GFP-HepG2 cells.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Immunology
Qiaoling Song, Shyamasree Datta, Xue Liang, Xiaohan Xu, Paul Pavicic, Xiaonan Zhang, Yuanyuan Zhao, Shan Liu, Jun Zhao, Yuting Xu, Jing Xu, Lihong Wu, Zhihua Wu, Minghui Zhang, Zhan Zhao, Chunhua Lin, Yuxin Wang, Peng Han, Peng Jiang, Yating Qin, Wei Li, Yingying Zhang, Yonglun Luo, Ganes Sen, George R. Stark, Chenyang Zhao, Thomas Hamilton, Jinbo Yang
Summary: We investigated the role of IFN-I in the myeloid compartment during acetaminophen overdose-induced acute liver injury (APAP-ALI) through single-cell RNA sequencing. We identified IFN-I-dependent transcriptional programs that promote efficient liver repair by facilitating the maturation of restorative macrophages. Our findings suggest the therapeutic potential of IFN-I in the treatment of APAP-ALI.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
