Article
Clinical Neurology
Thais Armangue, Gemma Olive-Cirera, Eugenia Martinez-Hernandez, Maria Rodes, Vicente Peris-Sempere, Mar Guasp, Raquel Ruiz, Eduard Palou, Azucena Gonzalez, Ma angeles Marcos, Maria Elena Erro, Luis Bataller, Inigo Corral-Corral, Jesus Planaguma, Eva Caballero, Alexandru Vlagea, Jie Chen, Paul Bastard, Marie Materna, Astrid Marchal, Laurent Abel, Aurelie Cobat, Laia Alsina, Claudia Fortuny, Albert Saiz, Emmanuel Mignot, Adeline Vanderver, Jean-Laurent Casanova, Shen-Ying Zhang, Josep Dalmau, Spanish HSE Study Grp
Summary: Patients with herpes simplex virus encephalitis often develop neuronal autoantibody-associated encephalitis post-infection. This study found that risk factors for post-HSE AE may include genetic variants, HLA haplotypes, and the blood innate immune response against HSV. These findings have potential clinical applications for the diagnosis and monitoring of HSE complications.
Article
Cell Biology
Ilkka Fagerlund, Antonios Dougalis, Anastasia Shakirzyanova, Mireia Gomez-Budia, Anssi Pelkonen, Henna Konttinen, Sohvi Ohtonen, Mohammad Feroze Fazaludeen, Marja Koskuvi, Johanna Kuusisto, Damian Hernandez, Alice Pebay, Jari Koistinaho, Tuomas Rauramaa, Sarka Lehtonen, Paula Korhonen, Tarja Malm
Summary: Human cerebral organoids derived from induced pluripotent stem cells can mimic the development of the cerebral cortex. By transplanting erythromyeloid progenitors differentiated from induced pluripotent stem cells, microglia-like cells can be formed in the organoids, promoting neuronal and network maturation through interaction with synaptic material.
Review
Veterinary Sciences
Bertrand Pain, Camille Baquerre, Muriel Coulpier
Summary: The brain is a complex organ, and the development of brain organoid models is helping to study various new topics in neuroscience, including brain development, neurodegenerative diseases, neurodevelopmental diseases, tumors, and infectious diseases affecting the brain. Current research is mainly focused on human cerebral organoids, but there is a growing interest in establishing similar models in other species.
VETERINARY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jon B. Suzich, Sean R. Cuddy, Hiam Baidas, Sara Dochnal, Eugene Ke, Austin R. Schinlever, Aleksandra Babnis, Chris Boutell, Anna R. Cliffe
Summary: HSV establishes a restricted latent infection in primary murine neurons in the presence of type I interferon, with PML-NBs forming and persisting with IFN treatment. The viral genomes retain a memory of the IFN response during de novo infection, leading to differential subnuclear positioning and restricting their ability to reactivate.
Article
Developmental Biology
Stephanie M. Bilinovich, Katie L. Uhl, Kristy Lewis, Xavier Soehnlen, Michael Williams, Daniel Vogt, Jeremy W. Prokop, Daniel B. Campbell
Summary: Research has shown that in utero exposure to chemicals such as diesel particulate matter (DPM) increases the risk of autism spectrum disorder. Transcriptomic analysis of DPM-exposed human-induced pluripotent stem cell-derived cerebral organoids revealed alterations in mitochondrial function and cellular respiration during early brain development, potentially contributing to developmental disorders like ASD.
DEVELOPMENTAL NEUROSCIENCE
(2021)
Article
Neurosciences
Philip L. Yates, Kendra Case, Xiaohuan Sun, Kimberly Sullivan, Peter W. Baas, Liang Qiang
Summary: Approximately 30% of Gulf War veterans suffer from Gulf War Illness (GWI), which is caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors. Using induced pluripotent stem cells derived from veterans with or without GWI, researchers have generated cerebral organoids that resemble the human brain. These organoids, when treated with GW toxicants, display cognitive deficits and other indicators consistent with GWI, suggesting their potential for studying cellular responses and developing personalized medicine approaches.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Zhijian Zhang, Richard O'Laughlin, Hongjun Song, Guo-Li Ming
Summary: The technology of brain organoids derived from human pluripotent stem cells allows the study of human brain development and disorders. This review focuses on the patterning of human stem cell-derived brain organoids, providing an overview of the procedures to generate them and highlighting recent protocols and chemical cues. Limitations and potential improvements of this technology are also discussed.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Article
Environmental Sciences
Shuangquan Wen, Li Wang, Chaofan Zhang, Ruilong Song, Hui Zou, Jianhong Gu, Xuezhong Liu, Jianchun Bian, Zongping Liu, Yan Yuan
Summary: Cadmium is an environmental pollutant with neurotoxicity. This study found that mitochondrial dysfunction leads to mitophagy and apoptosis, while inhibiting cyclosporine A exacerbates cell apoptosis. Similar results were observed in in vivo experiments. The study suggests that PINK1/Parkin-mediated mitophagy plays an important role in neuroprotection.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Plant Sciences
Yue Yuan, Peng Sheng, Bo Ma, Bingjie Xue, Mengmeng Shen, Ling Zhang, Dan Li, Jincai Hou, Junguo Ren, Jianxun Liu, Bing Chun Yan, Yunyao Jiang
Summary: This study elucidated the mechanisms by which Yiqi Tongluo Granule (YQTL) protects against ischemic stroke by combining network pharmacology, multi-omics, and molecular biology. YQTL significantly reduced infarction volume and improved neurological function in mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Network pharmacology and multi-omics analysis revealed that the 15 active ingredients of YQTL regulated 19 pathways via 82 targets, and further analysis suggested that YQTL protected against CIRI through the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway.
Article
Immunology
Fanny Onodi, Lucie Bonnet-Madin, Laurent Meertens, Lea Karpf, Justine Poirot, Shen-Ying Zhang, Capucine Picard, Anne Puel, Emmanuelle Jouanguy, Qian Zhang, Jerome Le Goff, Jean-Michel Molina, Constance Delaugerre, Jean-Laurent Casanova, Ali Amara, Vassili Soumelis
Summary: Studies have shown that human pDCs can be efficiently activated by SARS-CoV-2 particles and may contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemical Research Methods
Gwendoline Lozachmeur, Aude Bramoulle, Antoine Aubert, Francois Studer, Julien Moehlin, Lucie Madrange, Frank Yates, Jean-Philippe Deslys, Marco Antonio Mendoza-Parra
Summary: This study presents a low-cost strategy for manufacturing molecularly double-barcoded DNA arrays, enabling large-scale spatially resolved transcriptomics studies. It reveals gene expression heterogeneity throughout the tissue by applying this technique to spatially resolve gene expression in human brain organoids.
CELL REPORTS METHODS
(2023)
Article
Immunology
Zhi-Chao Sun, Zeyin Jiang, Xiaowen Xu, Meifeng Li, Qing Zeng, Ying Zhu, Shanghong Wang, Yuanyuan Li, Xiao-Li Tian, Chengyu Hu
Summary: The fish paralog proteins RNASEK-a and -b have been found to enhance type I interferon secretion and promote apoptosis, potentially through the phosphorylation of IRF3/IRF7 and eIF2 alpha, respectively.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Maud Tusseau, Ema Lovsin, Charlotte Samaille, Remi Pescarmona, Anne-Laure Mathieu, Maria-Cristina Maggio, Velma Selmanovic, Marusa Debeljak, Angelique Dachy, Gregor Novljan, Alexandre Janin, Louis Januel, Jean-Baptiste Gibier, Emilie Chopin, Isabelle Rouvet, David Goncalves, Nicole Fabien, Gillian Rice, Gaetan Lesca, Audrey Labalme, Paola Romagnani, Thierry Walzer, Sebastien Viel, Magali Perret, Yanick J. Crow, Tadej Avcin, Rolando Cimaz, Alexandre Belot
Summary: The interferon signaling in DNASE1L3 deficient patients is transient, unlike the anomalies observed in other diseases. DNASE1L3 deficiencies are associated with a broad phenotype including lupus nephritis and hypocomplementemic urticarial vasculitis.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Virology
Niluka Goonawardane, Laura Upstone, Mark Harris, Ian M. Jones
Summary: Tick-borne encephalitis virus (TBEV), spread by ticks, causes neurological disease. There is currently no specific treatment for TBE. The study generated a self-replicating TBEV replicon to compare highly pathogenic and low pathogenic TBEV strains. The study showed that the replicon of the highly pathogenic strain replicated more in mammalian cells, while the difference was related to the NS5 region. The study also found different host cell responses driven by NS5 that may contribute to the different clinical characteristics of TBEV strains.
JOURNAL OF VIROLOGY
(2022)
Review
Medicine, Research & Experimental
Jean-Laurent Casanova, Mark S. Anderson
Summary: Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying severe viral illnesses. In 2006, autoantibodies neutralizing type I IFNs due to rare inborn errors of autoimmune regulator (AIRE)-driven T cell tolerance were discovered, but not initially linked to any viral disease. These two lines of clinical investigation converged in 2020, revealing that deficiencies of type I IFN immunity accounted for a significant percentage of critical COVID-19 cases in unvaccinated individuals.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Cell Biology
Ryan O. Walters, Cathryn L. Haigh
Summary: Human cerebral organoids have emerged as an exciting model system in neurobiology, offering comprehensive replication of the human cerebral environment. They hold potential for investigating brain diseases and have shown promise in studying neurodegenerative diseases like prion disease.
CELL AND TISSUE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Anna Smith, Bradley R. Groveman, Clayton Winkler, Katie Williams, Ryan Walters, Jue Yuan, Wenquan Zou, Karin Peterson, Simote T. Foliaki, Cathryn L. Haigh
Summary: This study developed a cerebral organoid model to investigate the factors that trigger prion protein misfolding. The results showed that neither oxidative stress nor Herpes Simplex Type-1 virus can induce misfolding of E200K prion protein in the organoid system.
Article
Multidisciplinary Sciences
Jennifer Cable, Mark R. Denison, Margaret Kielian, William T. Jackson, Ralf Bartenschlager, Tero Ahola, Suchetana Mukhopadhyay, Daved H. Fremont, Richard J. Kuhn, Ashleigh Shannon, Meredith N. Frazier, Kwok-Yung Yuen, Carolyn B. Coyne, Katja C. Wolthers, Guo-Li Ming, Camy S. Guenther, Jasmine Moshiri, Sonja M. Best, John W. Schoggins, Kellie Ann Jurado, Gregory D. Ebel, Alexandra Schafer, Lisa F. P. Ng, Marjolein Kikkert, Alessandro Sette, Eva Harris, Peter A. C. Wing, Julie Eggenberger, Siddharth R. Krishnamurthy, Marcus G. Mah, Rita M. Meganck, Donghoon Chung, Sebastian Maurer-Stroh, Raul Andino, Bette Korber, Stanley Perlman, Pei-Yong Shi, Montserrat Barcena, Sophie-Marie Aicher, Michelle N. Vu, Devin J. Kenney, Brett D. Lindenbach, Yukiko Nishida, Laurent Renia, Evan P. Williams
Summary: Positive-strand RNA viruses, such as Zika virus, SARS, and SARS-CoV-2, have caused major outbreaks and epidemics in recent years. The Keystone Symposium Positive-Strand RNA Viruses, held on June 18-22, 2022, brought together researchers in various fields to discuss the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report provides concise summaries of the scientific discussions at the symposium.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Durbadal Ojha, Rahul Basu, Karin E. Peterson
Summary: The Zika virus is an arbovirus that causes placental insufficiency, microcephaly, and other neurological complications. Currently, there are no approved therapeutics to treat Zika virus infection. In this study, researchers examined how inhibiting cellular organelles or trafficking processes affected virus replication. They found that inducing endoplasmic reticulum stress could effectively inhibit virus production, suggesting it as a potential cellular target for antiviral development.
ANTIVIRAL RESEARCH
(2023)
Article
Genetics & Heredity
Simote T. T. Foliaki, Anna Smith, Benjamin Schwarz, Eric Bohrnsen, Catharine M. M. Bosio, Katie Williams, Christina D. D. Orru, Hailey Lachenauer, Bradley R. R. Groveman, Cathryn L. L. Haigh
Summary: Fatal familial insomnia (FFI) is a rare neurodegenerative disease caused by a genetic mutation in the prion protein (PrP). This mutation leads to brain cell dysfunction and is associated with astrogliosis and abnormal metabolism. Our findings suggest that the FFI mutation corrupts the function of PrP and disrupts cellular energy homeostasis, resulting in compromised neuronal activity.
Article
Multidisciplinary Sciences
Rahul Basu, Sundar Ganesan, Clayton W. Winkler, Sarah L. Anzick, Craig Martens, Karin E. Peterson, Iain D. C. Fraser
Summary: Viral encephalitis is characterized by the ability of virus to enter the central nervous system (CNS). This study found that La Crosse Virus primarily induces encephalitis in children rather than adults, which was also observed in mouse models. Transcriptomics and siRNA screening identified Connexin43 and EphrinA2 as key mediators of LACV-induced neuroinvasion and neurological disease.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Rosa C. Coldbeck-Shackley, Ornella Romeo, Sarah Rosli, Linden J. Gearing, Jodee A. Gould, San S. Lim, Kylie H. Van der Hoek, Nicholas S. Eyre, Byron Shue, Sarah A. Robertson, Sonja M. Best, Michelle D. Tate, Paul J. Hertzog, Michael R. Beard
Summary: This study investigates the role of a hormonally regulated type I interferon, IFN epsilon (IFNε), in controlling Zika virus (ZIKV) infection in the female reproductive tract. The researchers demonstrate that IFNε has anti-ZIKV properties through the use of IFNε KO mice, neutralising antibodies, and recombinant IFNε administered directly to the reproductive tract. Additionally, human cell lines derived from the reproductive tract were used to complement the in vivo studies. This work highlights the importance of IFNε as a key type I interferon in providing an antiviral environment in the female reproductive tract.
Article
Neurosciences
Bradley R. Groveman, Brent Race, Simote T. Foliaki, Katie Williams, Andrew G. Hughson, Chase Baune, Gianluigi Zanusso, Cathryn L. Haigh
Summary: Cerebral organoids (COs) derived from induced pluripotent stem cells have been shown to be susceptible to different subtypes of Creutzfeldt-Jakob disease (CJD) prions, making them a valuable model for studying human prion diseases. In a study with mouse models expressing human prion protein, it was found that the disease characteristics caused by the molecular subtype of the disease-associated prion protein were similar between CO-derived material and human brain material. This suggests that the prions generated in COs share strain characteristics with those in humans, supporting the use of COs for investigating human prion diseases and their subtypes.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Bradley R. Groveman, Benjamin Schwarz, Eric Bohrnsen, Simote T. Foliaki, James A. Carroll, Aleksandar R. Wood, Catharine M. Bosio, Cathryn L. Haigh
Summary: The absence of PrP protein inhibits the growth pathways of neural stem cells, resulting in decreased proliferation and increased senescence. This effect may be related to changes in the EGFR signaling pathway, decreased mitochondrial function, and blockages in cellular energy pathways.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Infectious Diseases
Alyssa B. Evans, Clayton W. Winkler, Sarah L. Anzick, Stacy M. Ricklefs, Dan E. Sturdevant, Karin E. Peterson
Summary: This study found that there is little restriction on Zika virus (ZIKV) diversity during transmission from the placenta to the fetus at early stages. However, there is a sharp decrease in ZIKV diversity in both fetal bodies and fetal brains at late stages, suggesting possible selection for certain variants during neuroinvasion of ZIKV into fetal brains.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Microbiology
Simote T. Foliaki, Cathryn L. Haigh
Article
Cell & Tissue Engineering
Katie Williams, Simote T. Foliaki, Brent Race, Anna Smith, Tina Thomas, Bradley R. Groveman, Cathryn L. Haigh
Summary: This study investigated the impact of cell therapy on sporadic Creutzfeldt-Jakob disease (sCJD) using a human cerebral organoid model. The results showed that while the treatment had minimal effects on prions, it had a beneficial impact on organoid function and restored electrophysiological parameters to normal levels. This suggests that cell therapy may have functional benefits in the treatment of human prion diseases.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
Guoli Shi, Abhilash I. Chiramel, Tiansheng Li, Kin Kui Lai, Adam D. Kenney, Ashley Zani, Adrian C. Eddy, Saliha Majdoul, Lizhi Zhang, Tirhas Dempsey, Paul A. Beare, Swagata Kar, Jonathan W. Yewdell, Sonja M. Best, Jacob S. Yount, Alex A. Compton
Summary: The use of rapalog drugs increases susceptibility to SARS-CoV-2 infection in immunocompromised individuals by promoting virus entry into cells and inhibiting the cell-intrinsic immune response.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Xi Wang, Cristina Cunha, Madeleine S. Grau, Shelly J. Robertson, Joao F. Lacerda, Antonio Campos Jr, Katrien Lagrou, Johan Maertens, Sonja M. Best, Agostinho Carvalho, Joshua J. Obar
Summary: This study investigates the role of the RIG-I-like receptor family in antifungal immunity against Aspergillus fumigatus and identifies the associations between polymorphisms in human MAYS and IFIH1 genes with invasive pulmonary aspergillosis. Additionally, it demonstrates that CD11c(+) Siglec F+ alveolar macrophages require Mavs expression for host resistance against A. fumigatus in a murine model.
JOURNAL OF IMMUNOLOGY
(2022)