Article
Biochemistry & Molecular Biology
Madison Edwards, Simpson Joseph
Summary: Fragile X Syndrome and certain manifestations of autism spectrum disorder are caused by improper RNA regulation due to a deficiency of fragile X mental retardation protein (FMRP). Fragile X related proteins (FXPs) play a crucial role in mRNA regulation and potential mRNA targets. This study investigated the function of FXPs in translational control using three potential mRNA targets, analyzing the binding site(s) of FXPs within the mRNA and their impact on translation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Dominic J. Vita, Cole J. Meier, Kendal Broadie
Summary: Glia play a crucial role in remodeling neural circuits during development. FMRP acts within neurons to activate glial insulin receptors, facilitating Draper- and Shrub-dependent neuronal clearance.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Chunzhu Song, Kendal Broadie
Summary: Drosophila models of neurological disease, particularly the FXS model, have greatly contributed to our understanding of the pathogenic mechanisms and neurological phenotypes of fragile X syndrome, and have provided potential therapeutic targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Andy Khamoui, Dorota Tokmina-Roszyk, Rafaela G. Feresin, Gregg B. Fields, Nishant P. Visavadiya
Summary: TMT-based quantitative proteomics was used to examine protein expression in skeletal muscle from mice with different severity of cancer cachexia. The study identified distinct mechanisms associated with cachexia severity and potential biomarkers and therapeutic targets.
Article
Cell Biology
Ji Geng, Tejinder Pal Khaket, Jie Pan, Wen Li, Yan Zhang, Yong Ping, Maria Inmaculada Cobos Sillero, Bingwei Lu
Summary: FMRP interacts with VDAC to regulate the formation and function of ERMCSs, which are critical for mito-Ca2+ homeostasis. Excessive ERMCS formation and ER-to-mitochondria Ca2+ transfer are observed in FXS. Inhibition of VDAC or other ERMCS components restores synaptic structure and function, rescues locomotion and cognitive deficits in FXS models.
DEVELOPMENTAL CELL
(2023)
Article
Multidisciplinary Sciences
Maria Mody, Yoann Petibon, Paul Han, Darshini Kuruppu, Chao Ma, Daniel Yokell, Ramesh Neelamegam, Marc D. Normandin, Georges El Fakhri, Anna-Liisa Brownell
Summary: Fragile X Syndrome is a neurodevelopmental disorder caused by the silencing of the Fragile X Mental Retardation gene, leading to reduced availability of mGluR5 receptors and excessive glutamate signaling. This study used PET-MR imaging to compare mGlu5 receptor availability in FXS patients and controls, finding significantly lower availability in the brains of FXS patients.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Sara G. Susco, Sulagna Ghosh, Patrizia Mazzucato, Gabriella Angelini, Amanda Beccard, Victor Barrera, Martin H. Berryer, Angelica Messana, Daisy Lam, Dane Z. Hazelbaker, Lindy E. Barrett
Summary: Down syndrome and fragile X syndrome may share underlying mechanisms, as evidenced by overlapping transcriptional perturbations and increased expression of select target proteins. Furthermore, upregulation of FMRP in Down syndrome patient cells can significantly reduce expression levels of candidate proteins and reverse global transcriptional perturbations.
Article
Multidisciplinary Sciences
Olivier Dionne, Audrey Lortie, Florence Gagnon, Francois Corbin
Summary: This study revealed a decrease in the rate of protein synthesis in peripheral blood mononuclear cells (PBMCs) of fragile X individuals compared to controls. The method used was highly reproducible, suggesting potential for broader application in cases of intellectual disability to assess abnormal protein synthesis as a common mechanism for impairment in synaptic plasticity and intellectual disability.
Article
Multidisciplinary Sciences
Sang S. Seo, Susana R. Louros, Natasha Anstey, Miguel A. Gonzalez-Lozano, Callista B. Harper, Nicholas C. Verity, Owen Dando, Sophie R. Thomson, Jennifer C. Darnell, Peter C. Kind, Ka Wan Li, Emily K. Osterweil
Summary: Dysregulated protein synthesis is a key contributing factor to the development of Fragile X syndrome. The authors of this study have identified a relationship between ribosome expression and the translation of long mRNAs, which is responsible for synaptic weakening in Fragile X syndrome.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Olivier Dionne, Francois Corbin
Summary: Fragile X syndrome is the most common inherited cause of intellectual disabilities and autism spectrum disorders, characterized by a wide range of behavioral, cognitive, and metabolic impairments with significant phenotypic heterogeneity among patients. Current tools for patient prognosis are lacking, leading researchers to identify potential proteomic biomarkers through analyzing the nascent proteome. This study suggests that the nascent proteome of PBMCs is a promising avenue for discovering biomarkers of FXS.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Asma Laroui, Luc Galarneau, Armita Abolghasemi, Serine Benachenhou, Rosalie Plantefeve, Fatima Zahra Bouchouirab, Jean Francois Lepage, Francois Corbin, Artuela Caku
Summary: This study compared the ability of quantitative gel zymography and ELISA to determine the abnormal levels of MMP-9 in individuals with FXS and its correlation with the clinical profile. The results showed that the plasma MMP-9 active form better discriminates individuals with FXS from healthy controls and correlates with the clinical profile.
SCIENTIFIC REPORTS
(2022)
Article
Obstetrics & Gynecology
C. Sonigo, A. Mayeur, M. Sadoun, M. Pinto, J. Benguigui, N. Frydman, S. Monnot, A. Benachi, J. Steffann, M. Grynberg
Summary: In females with FMR1 mutations or premutations undergoing preimplantation genetic testing (PGT), having seven or more mature oocytes in a cycle leads to an 83% chance of obtaining one or more healthy embryos. This study suggests that the number of mature oocytes is crucial in determining the success of transferring a healthy embryo in PGT cycles for FMR1 carriers.
HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Madison Edwards, Molly Huang, Simpson Joseph
Summary: This article reports a 99 nucleotide RNA target that is bound by all three FXPs with nanomolar equilibrium constants. The last 102 amino acids of FMRP, including the RGG motif, were found to be necessary and sufficient for binding this RNA target. This provides a new example of FMRP binding to non-G-quadruplex, non-homopolymer RNAs and offers potential targets for FXS therapeutics.
Article
Developmental Biology
Elolo Karen Nenonene, Mallorie Trottier-Lavoie, Mathilde Marchais, Alexandre Bastien, Isabelle Gilbert, Angus D. Macaulay, Edouard W. Khandjian, Alberto Maria Luciano, Valentina Lodde, Robert S. Viger, Claude Robert
Summary: RNA granules move through the transzonal projections in the cumulus cell network and this process is related to oocyte developmental competence, while RNA packaging involves Fragile X protein family's RNA-binding proteins. This study reveals the determinants of oocyte developmental competence and finds that the quality of the transzonal projection network in cumulus cells is associated with this competence. The study also identifies the roles of Fragile X-related proteins and their partnering protein families in regulating mRNA packaging, transport, and translation.
Article
Neurosciences
Susana R. Louros, Sang S. Seo, Beatriz Maio, Cristina Martinez-Gonzalez, Miguel A. Gonzalez-Lozano, Melania Muscas, Nick C. Verity, Jimi C. Wills, Ka Wan Li, Matthew F. Nolan, Emily K. Osterweil
Summary: In fragile X syndrome, excessive neuronal protein synthesis is a core pathophysiology, but an overall increase in protein expression is not observed. Surprisingly, although protein degradation through the ubiquitin proteasome system (UPS) is significantly increased, this contributes to pathological changes. Normalizing proteasome activity corrects excessive protein synthesis and hyperactivation of neurons in response to auditory stimulation, reducing the incidence and severity of audiogenic seizures in the mouse model. Excessive activation of the UPS pathway in fragile X neurons can be targeted for therapeutic intervention.
Article
Engineering, Biomedical
Dino Dvorak, Andrea Shang, Samah Abdel-Baki, Wendy Suzuki, Andre A. Fenton
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
(2018)
Article
Clinical Neurology
Steven R. Levine, Sarah Z. Weingast, Jeremy Weedon, Dimitre G. Stefanov, Patricia Katz, Dana Hurley, Scott E. Kasner, Pooja Khatri, Joseph P. Broderick, James C. Grotta, Edward Feldmann, Peter D. Panagos, Jose G. Romano, Riccardo Bianchi, Brett C. Meyer, Phillip A. Scott, Doojin Kim, Clotilde Balucani
Article
Biochemistry & Molecular Biology
Dino Dvorak, Basma Radwan, Fraser T. Sparks, Zoe Nicole Talbot, Andre A. A. Fenton
Article
Neurosciences
Rayna M. Harris, Hsin-Yi Kao, Juan Marcos Alarcon, Hans A. Hofmann, Andre A. Fenton
Editorial Material
Neurosciences
John L. Kubie, Eliott R. J. Levy, Andre A. Fenton
Review
Neurosciences
Syed Faraz Kazim, Joon Ho Seo, Riccardo Bianchi, Chloe S. Larson, Abhijeet Sharma, Robert K. S. Wong, Kirill Y. Gorbachev, Ana C. Pereira
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, with recent evidence suggesting that network abnormalities may play a key role in cognitive decline. A beta and tau are implicated in inducing network hyperexcitability, with genetic mutations leading to increased A beta production and hyperphosphorylated tau accumulation associated with seizures and epilepsy in patients. This review discusses the common and distinct roles of tau and A beta in neuronal hyperexcitability in Alzheimer's disease, proposing hypotheses for future experiments.
Article
Multidisciplinary Sciences
Ain Chung, Claudia Jou, Alejandro Grau-Perales, Eliott R. J. Levy, Dino Dvorak, Nida Hussain, Andre A. Fenton
Summary: Research suggests that cognitive control training can persistently alter hippocampal neural circuit function, facilitating learning of new tasks in novel environments and enhancing signal-to-noise ratio.
Editorial Material
Neurosciences
Ann M. Clemens, Kamran Khodakhah, Andre A. Fenton
Summary: Achieving academic success can vary depending on the individual, but it can ultimately be attained through professional effort and support that balance the hard work and joy of one's chosen path.
Review
Neurosciences
Andre A. Fenton, Jose R. Hurtado, Jantine A. C. Broek, Eunhye Park, Bud Mishra
Summary: This article explores the possibility of applying game theory to the analysis and modeling of neurobiological systems. By studying the basic properties and features of information asymmetric signaling games, it is possible to explain neurobiological phenomena, particularly cognitive variables in neuronal action potential discharge. The study highlights the need for integrating information and explanations across multiple scales of biological function in order to understand cognitive functions such as learning, memory, and perception. The article specifically focuses on the entorhinal cortex and hippocampus as interconnected brain regions in systems neuroscience, and uses examples of observed neuronal discharge to illustrate the challenges to the concept of information maximization.
Article
Cell Biology
Eliott Robert Joseph Levy, Simon Carrillo-Segura, Eun Hye Park, William Thomas Redman, Joserafael Hurtado, Sueyeon Chung, Andreantonio Fenton
Summary: Hippocampus place cells exhibit temporal unreliability and multimodal characteristics, suggesting that the ensemble cofiring spatial coding hypothesis with manifold dynamics is a more accurate representation than hypotheses based on stable place fields. A study on mouse CA1 ensembles showed that while place fields may remap, coactivity relationships generally remain consistent. Decoding location and environment from ensemble activity and cell-pair coactivity relationships is effective and improves with experience.
Article
Emergency Medicine
Benjamin H. Schnapp, Al'ai Alvarez, Riccardo Bianchi, Holly Caretta-Weyer, Corlin Jewell, Annahieta Kalantari, Eric Lee, Danielle Miller, Antonia Quinn
Summary: For residency recruitment, transparency with selection criteria, holistic application review, standardized letters of evaluation, and blinding applicant files for interviewers are considered some of the best practices.
AEM EDUCATION AND TRAINING
(2021)
Article
Neurosciences
Sasha L. Fulton, Changchi Hsieh, Tobias Atkin, Ryan Norris, Eric Schoenfeld, Panayiotis Tsokas, Andre Antonio Fenton, Todd Charlton Sacktor, Jeremy D. Coplan
Summary: Protein kinase M zeta (PKMζ) plays a crucial role in maintaining long-term potentiation and long-term memory, and may be affected by the emotional memory disruption caused by early-life adversity. Early-life adversity can lead to decreased expression of PKMζ in the ventral hippocampus, impacting the emotional responses of adult individuals.
Article
Neurosciences
Tara G. Chowdhury, Andre A. Fenton, Chiye Aoki
Summary: The study shows that food restriction, exercise, and a combination of both during mid-adolescence are all beneficial in reducing anxiety-like behavior and improving spatial cognition, with subtle differences in the timing of their effects, possibly reflecting the protracted maturation of the hippocampus.
Article
Neurosciences
Eliott R. J. Levy, Kally C. O'Reilly, Andre A. Fenton
Meeting Abstract
Clinical Neurology
Clotilde Balucani, Sarah Z. Weingast, Jeremy Weedon, Dimitre G. Stefanov, Patricia Katz, Dana Hurley, Pooja Khatri, Joseph P. Broderick, Scott E. Kasner, James C. Grotta, Edward Feldmann, Peter D. Panagos, Jose G. Romano, Riccardo Bianchi, Brett C. Meyer, Phillip A. Scott, Doojin Kim, Steven R. Levine