Article
Biology
Aoi Ichiyama, Samuel Mestern, Gabriel B. Benigno, Kaela E. Scott, Brian L. Allman, Lyle Muller, Wataru Inoue
Summary: This study reveals the mechanism underlying the activity state transition of hypothalamic paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons during stress response, using a combination of electrophysiology and computational modeling.
Article
Biochemistry & Molecular Biology
Kwan Young Lee, Haohan Wang, Yeeun Yook, Justin S. Rhodes, Catherine A. Christian-Hinman, Nien-Pei Tsai
Summary: The study identifies p53 as a novel transcription factor involved in synaptic potentiation and behavior. Knocking down p53 affects surface levels of AMPAR and hippocampal synaptic plasticity, promotes repetitive behavior, and reduces sociability. Moreover, it impairs hippocampus-dependent learning and memory. These learning-associated defects are more pronounced in male mice.
MOLECULAR PSYCHIATRY
(2023)
Article
Biology
Catia A. P. Silva, Annik Yalnizyan-Carson, M. Victoria Fernandez Busch, Mike van Zwieten, Matthijs Verhage, Christian Lohmann
Summary: During early development, mitochondrial motility decreases as neuronal activity frequency increases, with individual synaptic transmission events leading to local mitochondrial arrest. Pharmacological stimulation of synaptic vesicle release stops mitochondrial motility, suggesting the requirement of an unidentified factor co-released with glutamate.
Article
Multidisciplinary Sciences
Yuki Matsushita, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Shion Orikasa, Mizuki Nagata, Sunny Y. Wong, Joshua D. Welch, Wanida Ono, Noriaki Ono
Summary: In endochondral bone development, osteoblasts and bone marrow stromal cells have dual origins in fetal cartilage and its surrounding perichondrium. This study shows that perichondrial cells are destined to become adipocyte-biased stromal cells, indicating that marrow stromal compartments are defined by their cells of origin.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Francesco Petrelli, Tamara Zehnder, Anthony Laugeray, Sarah Mondoloni, Corrado Cali, Luca Pucci, Alicia Molinero Perez, Bianca Maria Bondiolotti, Eva De Oliveira Figueiredo, Glenn Dallerac, Nicole Deglon, Bruno Giros, Lorenzo Magrassi, Jean-Pierre Mothet, Manuel Mameli, Linda D. Simmler, Paola Bezzi
Summary: This study investigates the relationship between VMAT2 in astrocytes and the regulation of DA levels, finding that impairment of astrocytic control of DA leads to reduced DA levels, excessive grooming, and compulsive repetitive behaviors. The expression of VMAT2 in human PFC astrocytes validates the translational relevance of these findings.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Xingyu Yang, Zhiyu Chen, Xin Yin, Yuhua Wang, Yunqiang Yang, Yongping Yang
Summary: Calcium-dependent protein kinases (CDPKs) are crucial calcium ion (Ca2+) sensors in plants with significant roles in signal transduction, plant growth, development, and stress responses. In this study, we identified 24 CDPK genes in Dendrobium officinale and found that they formed four groups with similar structures. Our findings suggest functional divergence between homologous genes based on the differences in gene expression patterns following hormone treatments and yeast two-hybrid analysis. We also observed rapid accumulation of hydrogen peroxide (H2O2) and stomatal closure in response to salicylic acid (SA)/jasmonic acid (JA) stress. Furthermore, CDPK9-2 and CDPK20-4 were found to interact with Rboh D and Rboh H, respectively, and play a role in H2O2 generation and stomatal aperture regulation under SA/JA treatment. These results provide insights into the functional divergence of homologous genes in D. officinale.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kenichi Ishii, Matteo Cortese, Xubo Leng, Maxim N. Shokhirev, Kenta Asahina
Summary: This study reveals the genetic and neuronal mechanisms by which the nervous system suppresses aggression in a social experience-dependent manner, highlighting the importance of this process for maintaining animal fitness.
Article
Biochemistry & Molecular Biology
Sarah Cheng, Salwan Butrus, Liming Tan, Runzhe Xu, Srikant Sagireddy, Joshua T. Trachtenberg, Karthik Shekhar, S. Lawrence Zipursky
Summary: This study explores the role of postnatal experience in shaping cortical circuitry at the level of cell types in the mouse primary visual cortex. The findings suggest that vision selectively drives the development of upper-layer glutamatergic cell types, while deeper-layer cell types are established prior to eye opening. Furthermore, vision also influences the formation of a spatial continuum of L2/3 cell types through the regulation of specific gene expression programs. One of these vision-dependent genes, Igsf9b, is crucial for the normal development of binocular responses in L2/3.
Article
Plant Sciences
S. Gokul Babu, Deependra Singh Gohil, Swarup Roy Choudhury
Summary: The study identified 52 putative cyclin-dependent kinases (CDKs) and CDK-like (CDKLs) genes in cultivated peanut and its diploid parents. These genes are involved in various biological processes such as cell cycle progression, transcriptional regulation, DNA repair, abiotic stress and defense responses. The CDK and CDKL genes showed diverse expression patterns in different peanut tissues and were down-regulated under ABA, PEG and mannitol treatments.
Article
Biology
Ana Gutierrez-Franco, Franz Ake, Mohamed N. Hassan, Natalie Chaves Cayuela, Loris Mularoni, Mireya Plass
Summary: The critical step in single-cell transcriptomics is sample preparation. Different preservation methods show varying effects on cell quality and expression biases. In this study, methanol fixation is identified as the preferred method for droplet-based single-cell transcriptomics experiments on neural cell populations derived from induced pluripotent stem cells.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Isabella Farhy-Tselnicker, Matthew M. Boisvert, Hanqing Liu, Cari Dowling, Galina A. Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N. Shokhirev, Joseph R. Ecker, Nicola J. Allen
Summary: Research has shown that astrocytes regulate the formation and function of neuronal synapses during development through multiple signals, with some signals showing differential temporal and layer-enriched expression, regulated by neuronal activity. Alterations in astrocyte signaling lead to changes in the expression of synapse-regulating genes and synaptic development. Single-nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, as well as a cassette of genes that show layer-specific enrichment. It highlights the importance of coordinated signaling between astrocytes and neurons in the development of cortical circuits.
Article
Multidisciplinary Sciences
Evan J. Brettrager, Arthur W. Meehan, Charles N. Falany, Robert C. A. M. van Waardenburg
Summary: Through the yeast model system, it has been found that ectopic expression of SULT4A1 leads to correct subcellular localization and functional activity. The expression of SULT4A1 promotes colony formation and protects cells from oxidative stress, which is dependent on the presence of extracellular sulfate.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Qiqi Li, Yangan Huo, Siqi Wang, Liu Yang, Qifa Li, Xing Du
Summary: This study reveals that TGF-beta 1 alters the lncRNA transcriptome in a SMAD4-dependent manner, and shows that lncRNAs mediate the functions of TGF-beta 1 in granulosa cells, contributing to a better understanding of the epigenetic regulation of female fertility.
CELL PROLIFERATION
(2023)
Review
Biochemistry & Molecular Biology
Yves Van de Peer, Tia-Lynn Ashman, Pamela S. Soltis, Douglas E. Soltis
Summary: Polyploidy is hypothesized to play a role in both evolutionary dead-ends and diversification. Research suggests that whole-genome duplications may be linked with extinction events or global changes, while polyploids thrive in harsh environments. Biotic interactions, particularly with pathogens or mutualists, have differing effects on polyploids compared to nonpolyploids. Stress response is identified as a key factor in the establishment and success of polyploidy.
Article
Cell Biology
Darshan Sapkota, Mandy S. J. Kater, Kristina Sakers, Kayla R. Nygaard, Yating Liu, Sarah K. Koester, Stuart B. Fass, Allison M. Lake, Rohan Khazanchi, Rana R. Khankan, Mitchell C. Krawczyk, August B. Smit, Susan E. Maloney, Mark H. G. Verheijen, Ye Zhang, Joseph D. Dougherty
Summary: Neuronal activity can regulate transcriptional and translational responses in astrocytes, providing an additional mechanism for astrocytes to dynamically modulate nervous system functioning.
Article
Neurosciences
Yifei Yang, Sam A. Booker, James M. Clegg, Idoia Quintana-Urzainqui, Anna Sumera, Zrinko Kozic, Owen Dando, Sandra Martin Lorenzo, Yann Herault, Peter C. Kind, David J. Price, Thomas Pratt
Summary: This study combines bioinformatics analysis of human foetal cerebral cortex gene expression data with anatomical and electrophysiological analysis of a 16p11.2(+/-) rat model to investigate the impact of genetic risk factors on the development of inhibitory neurons. The study identifies a subset of human interneurons vulnerable to mutations causing autism and reports interneuron phenotypes in post-natal 16p11.2(+/-) rats.
Review
Biochemistry & Molecular Biology
Kyle S. Wardlaw, Giles E. Hardingham
Summary: The brain is a complex organ with various types of cells. Each cell type's functions are influenced by each other, and neurons control the properties of astrocytes to alter their homeostatic capacity. Astrocytes play a critical role in sustaining functional neuronal circuits and their functions can be regulated by signals from neurons. Understanding these signals could potentially be used to promote astrocyte-mediated neurosupport in brain disorders.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Endocrinology & Metabolism
Moritz Steinruecke, Rebecca Murphy Lonergan, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Blanca Diaz-Castro, Maria Stavrou
Summary: There is strong evidence suggesting blood-brain and blood-spinal cord barrier dysfunction in early stages of neurodegenerative diseases, such as ALS. In ALS, mitochondrial dysfunction, astrocyte pathology, and neuroinflammation are believed to contribute to impairment of the blood-central nervous system barrier (BCNSB). Mitochondrial dysfunction leads to motor neuron death, astrocytes play key roles at the barrier and exhibit inflammatory markers, and factors like TDP-43 pathology and systemic inflammation affect BCNSB integrity. Understanding BCNSB dysfunction in ALS has translational implications for biomarker development, restoration approaches, and in vitro modeling of the neurogliovascular system.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Medicine, General & Internal
Charis Wong, Jenna M. Gregory, Jing Liao, Kieren Egan, Hanna M. Vesterinen, Aimal Ahmad Khan, Maarij Anwar, Caitlin Beagan, Fraser S. Brown, John Cafferkey, Alessandra Cardinali, Jane Yi Chiam, Claire Chiang, Victoria Collins, Joyce Dormido, Elizabeth Elliott, Peter Foley, Yu Cheng Foo, Lily Fulton-Humble, Angus B. Gane, Stella A. Glasmacher, Aine Heffernan, Kiran Jayaprakash, Nimesh Jayasuriya, Amina Kaddouri, Jamie Kiernan, Gavin Langlands, D. Leighton, Jiaming Liu, James Lyon, Arpan R. Mehta, Alyssa Meng, Vivienne Nguyen, Na Hyun Park, Suzanne Quigley, Yousuf Rashid, Andrea Salzinger, Bethany Shiell, Ankur Singh, Tim Soane, Alexandra Thompson, Olaf Tomala, Fergal M. Waldron, Bhuvaneish T. Selvaraj, Jeremy Chataway, Robert Swingler, Peter Connick, Suvankar Pal, Siddharthan Chandran, Malcolm Macleod
Summary: This study presents a systematic and structured evidence-based approach to select the first two drugs for evaluation in the MND-SMART trial. Through a comprehensive evaluation of clinical studies and animal models, memantine and trazodone were selected as the first two drugs based on supportive evidence.
Article
Developmental Biology
Yushi Redhead, Dorota Gibbins, Eva Lana-Elola, Sheona Watson-Scales, Lisa Dobson, Matthias Krause, Karen J. Liu, Elizabeth M. C. Fisher, Jeremy B. A. Green, Victor L. J. Tybulewicz
Summary: Down syndrome (DS) is a common human chromosomal abnormality that leads to various phenotypic features, including craniofacial dysmorphology. Through analysis of a DS mouse model and genetic mapping, it was found that four regions on mouse chromosome 16, which correspond to Hsa21 in humans, contain dosage-sensitive genes that contribute to DS craniofacial abnormalities, with Dyrk1a identified as one of the causative genes. The study revealed that the earliest and most severe defects in the DS mouse skulls occur in bones of neural crest origin, and that abnormal mineralization of the skull base synchondroses is present. Additionally, increased dosage of Dyrk1a was found to result in decreased proliferation of neural crest cells and a reduction in size and cellularity of the frontal bone primordia.
Article
Cell Biology
Kourtney Sloan, Jared Thomas, Matthew Blackwell, Deanna Voisard, Eva Lana-Elola, Sheona Watson-Scales, Daniel L. Roper, Joseph M. Wallace, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Randall J. Roper
Summary: This study investigates the effects of triplicated genes on mouse skeletal phenotypes and finds that they can both improve and worsen bone deficits.
DISEASE MODELS & MECHANISMS
(2023)
Review
Chemistry, Medicinal
Jessica Merjane, Roger Chung, Rickie Patani, Leszek Lisowski
Summary: Despite the mysterious etiology, differentiated treatments are required for ALS to address both familial and sporadic cases. Targeting mechanisms of defective protein homeostasis and RNA processing, as well as exploring the use of gene therapy through adeno-associated virus (AAV) for gene delivery to the CNS, might provide potential therapeutic interventions. Overall, there is a strong need for disease modifying treatments for ALS that can effectively treat the full spectrum of cases.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Clinical Neurology
Rickie Patani, Giles E. Hardingham, Shane A. Liddelow
Summary: Therapies that prevent neuronal loss in neuroinflammation and neurodegenerative disease are still elusive. This review highlights the importance of 'omics' technologies in characterizing the functional states of reactive astrocytes in different pathological scenarios.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Irene Molina-Gonzalez, Rebecca K. Holloway, Zoeb Jiwaji, Owen Dando, Sarah A. Kent, Katie Emelianova, Amy F. Lloyd, Lindsey H. Forbes, Ayisha Mahmood, Thomas Skripuletz, Viktoria Gudi, James A. Febery, Jeffrey A. Johnson, Jill H. Fowler, Tanja Kuhlmann, Anna Williams, Siddharthan Chandran, Martin Stangel, Andrew J. M. Howden, Giles E. Hardingham, Veronique E. Miron
Summary: Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions. This study shows that the interaction between astrocytes and mature myelin-forming oligodendrocytes is crucial for remyelination. Astrocytes support the survival of regenerating oligodendrocytes by downregulating the Nrf2 pathway and activating the cholesterol biosynthesis pathway. This discovery reveals a drug strategy for central nervous system regeneration by targeting the astrocyte-oligodendrocyte interaction.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Shreya Das Sharma, Bharath Kumar Reddy, Rakhi Pal, Tuula E. Ritakari, James D. Cooper, Bhuvaneish T. Selvaraj, Peter C. Kind, Siddharthan Chandran, David J. A. Wyllie, Sumantra Chattarji
Summary: Previous pre-clinical studies on fragile X syndrome (FXS) have mainly focused on neurons and the role of glia has been largely unexplored. This study investigates the astrocytic regulation of aberrant firing in FXS neurons derived from human pluripotent stem cells. It was found that co-culturing FXS cortical neurons with FXS astrocytes led to frequent short-duration bursts of action potentials, while co-culturing control neurons with control astrocytes resulted in less frequent, longer-duration bursts. The astrocyte genotype was found to determine the firing phenotype of the neurons, and the astroglial-derived protein, S100b, played a role in restoring normal firing.
Article
Cell Biology
Bita Massih, Alexander Veh, Maren Schenke, Simon Mungwa, Bettina Seeger, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Peter Reinhardt, Jared Sterneckert, Andreas Hermann, Michael Sendtner, Patrick Lueningschroer
Summary: This article introduces a human neuromuscular co-culture system that enables the formation of neuromuscular junctions by differentiating induced pluripotent stem cells into motor neurons and 3D skeletal muscle tissue. The system is suitable for modeling the pathophysiology of motor neuron diseases and has been used to study the synaptic coupling and muscle contraction in Amyotrophic Lateral Sclerosis (ALS). This in vitro model recapitulates aspects of human physiology and is of great importance for studying human motor neurons in health and disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Clinical Neurology
Christy Hung, Rickie Patani
Summary: This study uses a patient-derived stem cell model to uncover disease mechanisms in a type of dementia closely related to motor neuron disease called FTD. Specifically, they show that the increase of a particular type of tau protein-called the 4R isoform-drives degeneration of nerve cells, thereby causing the disease.
Article
Plant Sciences
Zeenat B. Noordally, Matthew M. Hindle, Sarah F. Martin, Daniel D. Seaton, T. Ian Simpson, Thierry Le Bihan, Andrew J. Millar
Summary: This study compared transcriptome data with partial proteome and phosphoproteome data from the alga Ostreococcus tauri. They found that 10% of quantified proteins and two-thirds of phosphorylated proteins showed rhythmic changes. Mathematical modeling indicated that light-stimulated protein synthesis could explain the clustering of protein peaks during the daytime. The study also observed anticipatory phosphorylation before dawn, suggesting clock-regulated phosphodawn prepares the cells for daytime functions.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Neurosciences
Oliver J. Ziff, Jasmine Harley, Yiran Wang, Jacob Neeves, Giulia Tyzack, Fairouz Ibrahim, Mark Skehel, Anob M. Chakrabarti, Gavin Kelly, Rickie Patani
Summary: This study investigates the mislocalization of mRNA and protein in ALS patients. The findings suggest a link between RBP mislocalization and mRNA redistribution in ALS motor neurons. Treatment with the VCP ATPase inhibitor ML240 partially restores mRNA and protein localization and reduces oxidative stress and DNA damage.
Article
Biochemistry & Molecular Biology
Giuseppe Nicastro, Giancarlo Abis, Pierre Klein, Sofia Esteban-Serna, Christopher Gallagher, Belen Chaves-Arquero, Yuyang Cai, Angelo Miguel Figueiredo, Stephen R. Martin, Rickie Patani, Ian A. Taylor, Andres Ramos
Summary: m6A methylation is an important regulatory layer in organismal development and is associated with various cancers and neuro-pathologies. RNA binding proteins, known as m6A readers, integrate the information encoded by m6A methylation into existing RNA regulatory networks. This study reveals that the reader IMP1 recognizes m6A through a specific hydrophobic platform, forming a stable and high-affinity interaction. The recognition is conserved across evolution and independent of the sequence context, but builds upon the strong sequence specificity of IMP1 for GGAC RNA. These findings propose a context-dependent role for methylation in the recognition of IMP1 targets, dependent on the cellular concentration of IMP1, as opposed to the YTH proteins.
NUCLEIC ACIDS RESEARCH
(2023)
