Targeting protein kinase C-α prolongs survival and restores liver function in sepsis: Evidence from preclinical models by Ling Xiong, Dustin Beyer, Na Liu, Tina Lehmann, Sophie Neugebauer, Sascha Schaeuble, Oliver Sommerfeld, Philipp Ernst, Carl-Magnus Svensson, Sandor Nietzsche, Sebastian Scholl, Tony Bruns, Nikolaus Gaßler, Markus H. Gräler, Marc Thilo Figge, Gianni Panagiotou, Michael Bauer, Adrian T. Press

“…Using a preclinical murine sepsis model, we found that both PKCα knockout and the use of a PKCα-inhibitor midostaurin successfully restored liver function without hindering the host’s response or ability to clear the pathogen, highlighting PKCα’s vital role in excretory liver failure. …”
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Dysfunction of ATP7B Splicing Variant Caused by Enhanced Interaction With COMMD1 in Wilson DiseaseSummary by Donghu Zhou, Huaduan Zi, Xiaoxi Yang, Xiaojin Li, Yanmeng Li, Anjian Xu, Bei Zhang, Wei Zhang, Xiaojuan Ou, Jidong Jia, Jian Huang, Hong You

“…Methods: The splicing assay and RNA pull-down were performed to explore the mechanism of the aberrant splicing. The ATP7B knockout HuH-7 cell line and Atp7b-/- mice were created, and the functional consequence of the mutant ATP7B were evaluated in vitro and in vivo. …”
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LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK by Joanna Filipowska, Zelda Cisneros, Sneha S. Varghese, Nancy Leon-Rivera, Peng Wang, Randy Kang, Geming Lu, Yate-Ching Yuan, Hung-Ping Shih, Supriyo Bhattacharya, Sangeeta Dhawan, Adolfo Garcia-Ocaña, Nagesha Guthalu Kondegowda, Rupangi C. Vasavada

“…Using Lgr4fl/fl and Lgr4fl/fl/Rankfl/fl × Ins1-Cre mice we generated β-cell-specific conditional knockout (cko) mice to test the role of LGR4 and its interaction with RANK in vivo under basal and stress-induced conditions. …”
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CaMKII-dependent non-canonical RIG-I pathway promotes influenza virus propagation in the acute-phase of infection by Shinichiro Hama, Miho Watanabe-Takahashi, Hiroki Nishimura, Jumpei Omi, Masakazu Tamada, Takashi Saitoh, Katsumi Maenaka, Yuta Okuda, Aoi Ikegami, Asami Kitagawa, Koudai Furuta, Kana Izumi, Eiko Shimizu, Takashi Nishizono, Makoto Fujiwara, Tomohiro Miyasaka, Shigeo Takamori, Hiroshi Takayanagi, Keizo Nishikawa, Toshihiko Kobayashi, Noriko Toyama-Sorimachi, Makoto Yamashita, Toshiya Senda, Takatsugu Hirokawa, Haruhiko Bito, Kiyotaka Nishikawa

“…Downstream of the RIG-I pathway activated TBK1 and then IRF3, which induced small but sufficient amounts of transcripts of the genes for IFN α/β to provide the capped 5’-ends that were used preferentially as primers to synthesize viral mRNAs by the cap-snatching mechanism. Importantly, knockout of RIG-I in cells almost completely inhibited the expression of IFN mRNAs and subsequent viral NP mRNA early in infection (up to 6 h after infection), which then protected cells from cytopathicity 24 h after infection. …”
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Binding of LncDACH1 to dystrophin impairs the membrane trafficking of Nav1.5 protein and increases ventricular arrhythmia susceptibility by Genlong Xue, Jiming Yang, Yang Zhang, Ying Yang, Ruixin Zhang, Desheng Li, Tao Tian, Jialiang Li, Xiaofang Zhang, Changzhu Li, Xingda Li, Jiqin Yang, Kewei Shen, Yang Guo, Xuening Liu, Guohui Yang, Lina Xuan, Hongli Shan, Yanjie Lu, Yang Baofeng, Zhenwei Pan

“…The opposite data of western blot, immunofluorescent staining and patch clamp were collected from lncDach1 cardiomyocyte conditional knockout (lncDach1-cKO) mice. Moreover, increased ventricular arrhythmia susceptibility was observed in lncDach1-TG mice in vivo and ex vivo. …”
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Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation by Minji Kang, Sang Ho Yoon, Minkyung Kang, Seung Pyo Park, Woo Seok Song, Jungho Kim, Seungha Lee, Da-ha Park, Jae-man Song, Beomsue Kim, Kyung Hee Park, Eun-Hye Joe, Hyun Goo Woo, Seong Hoe Park, Bong-Kiun Kaang, Dohyun Han, Yong-Seok Lee, Myoung-Hwan Kim, Young Ho Suh

“…Additionally, Cd99l2 knockout mice exhibit impaired excitatory synaptic transmission and plasticity in the hippocampus, along with deficits in spatial memory and contextual fear conditioning. …”
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Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins by Maria Angelica Freitas-Cortez, Fatemeh Masrorpour, Hong Jiang, Iqbal Mahmud, Yue Lu, Ailing Huang, Lisa K. Duong, Qi Wang, Tiffany A. Voss, Claudia S. Kettlun Leyton, Bo Wei, Wai-Kin Chan, Kevin Lin, Jie Zhang, Efrosini Tsouko, Shonik Ganjoo, Hampartsoum B. Barsoumian, Thomas S. Riad, Yun Hu, Carola Leuschner, Nahum Puebla-Osorio, Jing Wang, Jian Hu, Michael A. Davies, Vinay K. Puduvalli, Cyrielle Billon, Thomas P. Burris, Philip L. Lorenzi, Boyi Gan, James W. Welsh

“…We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rora fl mice. …”
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The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models by Jaromir Novak, Zuzana Nahacka, Gabriela L. Oliveira, Petra Brisudova, Maria Dubisova, Sarka Dvorakova, Sona Miklovicova, Marketa Dalecka, Verena Puttrich, Lenka Grycova, Silvia Magalhaes-Novais, Catarina Mendes Correia, Jennifer Levoux, Ludek Stepanek, Jan Prochazka, David Svec, David Pajuelo Reguera, Guillermo Lopez-Domenech, Renata Zobalova, Radek Sedlacek, Mikkel G. Terp, Payam A. Gammage, Zdenek Lansky, Josef Kittler, Paulo J. Oliveira, Henrik J. Ditzel, Michael V. Berridge, Anne-Marie Rodriguez, Stepana Boukalova, Jakub Rohlena, Jiri Neuzil

“…We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed tumor formation after grafting ρ0 cancer cells. …”
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Atg5 deficiency in basophils improves metabolism in lupus mice by regulating gut microbiota dysbiosis by Jiaxuan Chen, Quanren Pan, Lu Lu, Xiaorong Huang, Shuting Wang, Xiaoxian Liu, Jiaqi Lun, Xiaowei Xu, Hongyong Su, Fengbiao Guo, Lawei Yang, Liuyong You, Haiyan Xiao, Wenying Luo, Hua-feng Liu, Qingjun Pan

“…Here, we investigated the effects of autophagic inhibition on the pathogenesis of basophils in SLE using Autophagy-related gene 5 (Atg5) knockout (Atg5 −/−) as an autophagic inhibitor. Specifically, we knocked out basophilic Atg5 in vivo to investigate its impact on lupus metabolism. …”
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Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury by Guihong Shi, Yiyao Cao, Jianye Xu, Bo Chen, Xu Zhang, Yanlin Zhu, Liang Liu, Xilei Liu, Luyuan Zhang, Yuan Zhou, Shenghui Li, Guili Yang, Xiao Liu, Fanglian Chen, Xin Chen, Jianning Zhang, Shu Zhang

“…Further experiments with PAD4 knockout mice confirmed that the reduction of NETs could substantially alleviate S100A8/A9-driven neuroinflammation. …”
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Placental growth factor modulates endothelial NO production and exacerbates experimental hepatopulmonary syndrome by Fabien Robert, Feriel Benchenouf, My Ngoc Ha, Alessandra Cuomo, Mina Ottaviani, Maxime Surbier, Raphaël Thuillet, Corinne Normand, Florent Dumont, Céline Verstuyft, Frederic Fiore, Frederic Guinut, Marc Humbert, Audrey Coilly, Emmanuel Gonzales, Olivier Sitbon, Ly Tu, Christophe Guignabert, Laurent Savale

“…Two rat models, common bile duct ligation (CBDL) and long-term partial portal vein ligation (PPVL), were used. Plgf-knockout (Plgf–/–) rats were generated using CRISPR-Cas9. …”
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Loss of protein C vs protein S results in discrepant thrombotic phenotypes by Chia-Jui Ku, Xinge Yu, Queena Y. Zhao, Steven J. Grzegorski, Jeffrey G. Daniel, Allison C. Ferguson, Jordan A. Shavit

“…This is consistent with the consumptive coagulopathy of zebrafish antithrombin 3 knockouts, which also results in spontaneous venous thrombosis. …”
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Differential Fasting Plasma Glucose and Ketone Body Levels in GHRKO versus 3xTg-AD Mice: A Potential Contributor to Aging-Related Cognitive Status? by Chelsea M. Griffith, Lauren N. Macklin, Andrzej Bartke, Peter R. Patrylo

“…Since the majority of brain nutrients come from the periphery, this study examined whether the capacity to regulate peripheral glucose levels and KB production differs in animals with successful cognitive aging (growth hormone receptor knockouts, GHRKOs) versus unsuccessful cognitive aging (the 3xTg-AD mouse model of Alzheimer’s disease). …”
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Genetic approaches to the investigation of serotonergic neuron functions in animals by U. S. Drozd, E. V. Shaburova, N. N. Dygalo

“…In particular, genetic knockouts of serotonin genes sert, pet1, and tph2 promoted the determination of their contribution to the development and functioning of the brain. …”
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FFAR4 (GPR120) Signaling Is Not Required for Anti-Inflammatory and Insulin-Sensitizing Effects of Omega-3 Fatty Acids by Simone Isling Pærregaard, Marianne Agerholm, Annette Karen Serup, Tao Ma, Bente Kiens, Lise Madsen, Karsten Kristiansen, Benjamin Anderschou Holbech Jensen

“…In the present study, we used Ffar4 knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucrose ω3-PUFA; or high fat, high sucrose ω6-PUFA diet for 36 weeks. …”
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Protein kinases MpkA and SepH transduce crosstalk between CWI and SIN pathways to activate protective hyphal septation under echinocandin cell wall stress by Alexander G. Doan, Jessica E. Schafer, Casey M. Douglas, Matthew S. Quintanilla, Meredith E. Morse, Harley Edwards, Walker D. Huso, Kelsey J. Gray, JungHun Lee, Joshua K. Dayie, Steven D. Harris, Mark R. Marten

“…More detailed investigations, with targeted knockouts of CWI and SIN signaling proteins, enabled us to identify crosstalk occurring between the CWI kinase, MpkA, and the SIN kinase, SepH. …”
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