Article
Biochemistry & Molecular Biology
Christopher T. Esapa, R. A. Jeffrey Mcilhinney, Adrian J. Waite, Matthew A. Benson, Jasmin Mirzayan, Henriett Piko, Agnes Herczegfalvi, Rita Horvath, Veronika Karcagi, Maggie C. Walter, Hanns Lochmueller, Pierre J. Rizkallah, Qi L. Lu, Derek J. Blake
Summary: FKRP gene mutations cause muscular dystrophies by disrupting protein folding and intracellular dynamics. Mutant FKRP forms disulfide-bonded aggregates and shows reduced intracellular mobility. Mutant FKRP exhibits differential associations with endoplasmic reticulum chaperones and affects the local protein environment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Clinical Neurology
Issa Alawneh, Ana Stosic, Hernan Gonorazky
Summary: This article discusses the study of limb girdle muscle dystrophies (LGMDs) using muscle magnetic resonance imaging (MRI) for diagnosis and understanding of the disease. A systematic review found that muscle MRI patterns have been described for 15 out of 17 types of LGMDs. Despite the challenging diagnosis of LGMDs, muscle MRI can aid in diagnosis. Larger cohorts of patients are needed to further enhance the application of muscle MRI in the neuromuscular field.
JOURNAL OF NEUROLOGY
(2023)
Article
Oncology
Yu Zhang, Takahiko Nishiyama, Eric N. Olson, Rhonda Bassel-Duby
Summary: Muscular dystrophies are a group of neuromuscular disorders with genetic causes that lead to muscle loss and degeneration. The CRISPR/Cas system offers a new path for treatment, potentially correcting genetic mutations permanently and benefiting skeletal muscle due to its post-mitotic and multinucleated features. However, challenges remain for translating CRISPR/Cas genome editing into a viable therapy for muscular dystrophies.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Immunology
Andrea Farini, Chiara Villa, Luana Tripodi, Mariella Legato, Yvan Torrente
Summary: Muscular dystrophies and inflammatory myopathies are muscular disorders characterized by progressive muscle weakness and mass loss, with shared features of inflammation and immune response. Immune mechanisms involved include complement cascade activation and auto-antibodies directed against muscular proteins.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell & Tissue Engineering
Carolina Ortiz-Cordero, Claudia Bincoletto, Neha R. Dhoke, Sridhar Selvaraj, Alessandro Magli, Haowen Zhou, Do-Hyung Kim, Anne G. Bang, Rita C. R. Perlingeiro
Summary: This study investigates the molecular mechanisms impaired by FKRP mutations in pluripotent stem cell-derived myotubes, revealing alterations in extracellular matrix receptor interactions, calcium signaling, PI3K-Akt pathway, and lysosomal function. The autophagy-lysosome pathway is significantly reduced in patient-specific LGMDR9 and WWS induced myotubes, while WWS myotubes show decreased ERK1/2 activity and increased apoptosis. These findings suggest that the autophagy-lysosome pathway and apoptosis may play a role in the pathogenesis of FKRP-associated muscular dystrophies.
Review
Biochemistry & Molecular Biology
Coralie Croissant, Romain Carmeille, Charlotte Brevart, Anthony Bouter
Summary: Muscular dystrophies are genetic disorders characterized by weakening and loss of skeletal muscle mass. ANXA proteins are important for membrane repair in cells, and dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Enrico Almici, Vanessa Chiappini, Aristides Lopez-Marquez, Carmen Badosa, Blanca Blazquez, David Caballero, Joan Montero, Daniel Natera-de Benito, Andres Nascimento, Monica Roldan, Anna Lagunas, Cecilia Jimenez-Mallebrera, Josep Samitier
Summary: This study engineered a personalized pre-clinical model of COL6-RDs using cell-derived matrices (CDMs) technology and found alterations in ECM structure and composition in COL6-RD patients. These models may serve as promising tools to explore the pathology of COL6-RDs, identify novel biomarkers, and investigate new therapeutic targets and treatments.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biology
Carolina Ortiz-Cordero, Alessandro Magli, Neha R. Dhoke, Taylor Kuebler, Sridhar Selvaraj, Nelio A. J. Oliveira, Haowen Zhou, Yuk Y. Sham, Anne G. Bang, Rita C. R. Perlingeiro
Summary: The study established a myogenic model derived from human induced pluripotent stem cells for WWS, showing that ribose and ribitol can promote functional recovery. Furthermore, a synergistic effect was observed when combining ribose/ribitol with NAD+, providing potential therapeutic options for WWS and other diseases associated with FKRP mutations.
Review
Cell Biology
Nicola Mosca, Sara Petrillo, Sara Bortolani, Mauro Monforte, Enzo Ricci, Fiorella Piemonte, Giorgio Tasca
Summary: Oxidative stress is a prominent factor in the pathophysiology of various muscle disorders, but specific mechanisms and targeted antioxidant therapies still require further research and clinical trials.
Article
Engineering, Biomedical
Nicolas Rose, Berenice Estrada Chavez, Surabhi Sonam, Thao Nguyen, Gianluca Grenci, Anne Bigot, Antoine Muchir, Benoit Ladoux, Bruno Cadot, Fabien Le Grand, Lea Trichet
Summary: We have developed a miniaturized 3D myotube culture chip that can monitor contraction at the single cell level. This technology requires significantly fewer starting materials than current systems and is crucial for evaluating the outcomes of therapeutic procedures for neuromuscular disorders.
Review
Biochemistry & Molecular Biology
Alan Rawls, Bridget K. Diviak, Cameron I. Smith, Grant W. Severson, Sofia A. Acosta, Jeanne Wilson-Rawls
Summary: Muscular dystrophies are genetic muscle-wasting disorders characterized by chronic inflammation and fibrotic scarring in muscle tissue. Duchenne muscular dystrophy, the most common form, is typically treated with anti-inflammatory glucocorticoids; however, their long-term use is limited by adverse side effects. Developing new pharmacotherapeutic approaches to reduce muscle damage and promote repair is crucial.
Article
Clinical Neurology
Susana Quijano-Roy, Jana Haberlova, Claudia Castiglioni, John Vissing, Francina Munell, Francois Rivier, Tanya Stojkovic, Edoardo Malfatti, Marta Gomez Garcia de la Banda, Giorgio Tasca, Laura Costa Comellas, Audrey Benezit, Helge Amthor, Ivana Dabaj, Clara Gontijo Camelo, Pascal Laforet, John Rendu, Norma B. Romero, Eliana Cavassa, Fabiana Fattori, Christophe Beroud, Jana Zidkova, Nicolas Leboucq, Nicoline Lokken, Angel Sanchez-Montanez, Ximena Ortega, Martin Kyncl, Corinne Metay, David Gomez-Andres, Robert Y. Carlier
Summary: Patients with LAMA2-RD exhibit a consistent pattern of abnormal muscle fat replacement in muscle imaging, which serves as a supportive diagnostic tool. Thigh muscles appear to be the most informative for assessing disease progression.
JOURNAL OF NEUROLOGY
(2022)
Review
Cell & Tissue Engineering
Juan M. Fernandez-Costa, Xiomara Fernandez-Garibay, Ferran Velasco-Mallorqui, Javier Ramon-Azcon
Summary: Muscular dystrophies are a group of disabling disorders characterized by muscle degeneration, for which there is currently no effective cure. Recent advances in bioengineering have led to the development of bioartificial muscles and tools for drug screening in skeletal muscle tissue engineering.
JOURNAL OF TISSUE ENGINEERING
(2021)
Article
Oncology
Massimo Ganassi, Francesco Muntoni, Peter S. Zammit
Summary: This study explores the effects of pathogenic mutations on satellite cell function in muscle diseases. The findings suggest that these mutations can directly or indirectly affect satellite cell function, leading to muscle pathology. The study introduces a classification of satellite cell-opathies, which helps in diagnosis, prognosis, and treatment development.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Rehabilitation
Laure Le Goff, Katherine G. Meilleur, Gina Norato, Pascal Rippert, Minal Jain, Margaret Fink, A. Reghan Foley, Melissa Waite, Sandra Donkervoort, Carsten G. Boennemann, Carole Vuillerot
Summary: The study found that the MFM showed strong responsiveness in individuals with LAMA2-RD and COL6-RD, and it is important for assessing muscle function in patients.
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
(2021)
Article
Anesthesiology
Pamela V. Andrade, Lucas S. Souza, Joilson M. Santos, Jose F. F. Alves, Claudia Lutke, Jose L. G. Amaral, Mariz Vainzof, Helga C. A. Silva
Summary: Thermoregulatory dysfunction induced by spinal cord injury may obscure the early diagnosis of malignant hyperthermia, leading to fatal outcomes.
CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE
(2022)
Review
Biochemistry & Molecular Biology
Mayana Zatz, Monize V. R. Silva, Mateus de Castro, Michel S. Naslavsky
Summary: This review summarizes previous genetic association studies and next-generation sequencing in elderly cohorts, discusses factors associated with healthy aging, and highlights the importance of studying non-European admixed populations and older individuals who recover from or remain asymptomatic to enhance our understanding of biological mechanisms associated with resistance against pathogens.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Juliana C. Correa-Velloso, Alessandra M. Linardi, Talita Glaser, Fernando J. Velloso, Maria P. Rivas, Renata E. P. Leite, Lea T. Grinberg, Henning Ulrich, Michael R. Akins, Silvana Chiavegatto, Luciana A. Haddad
Summary: In this study, the authors investigated the expression of Fmr1 exon 14 during rat nervous system development. Their results showed that skipping of exon 14 occurred mainly in the rat forebrain during the third embryonic week. This alternative splicing event may be part of combinatorial mechanisms downregulating the gene's expression in the late embryonic period. The authors also found that the decay of FMR1 mRNA without exon 14 is mediated by a pathway different from nonsense-mediated mRNA decay (NMD) and provided evidence of FMR1 mRNA stabilization by UPF1.
Article
Immunology
Fernando Janczur Velloso, Anna Wadhwa, Ekta Kumari, Ioana Carcea, Ozlem Gunal, Steven W. Levison
Summary: Epidemiological studies have shown that infections during pregnancy increase the risk of psychiatric disorders in offspring, and interleukin-6 (IL-6) has been implicated as a causal agent. This study aimed to investigate whether elevating IL-6 during a specific period of neural development would affect neurogenesis and lead to behavioral changes associated with neurodevelopmental disorders. The results demonstrate that transient increase in IL-6 during postnatal days 3-6 reduced neurogenesis and astrogliogenesis, and affected behavioral traits in adult male mice.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Cell & Tissue Engineering
Shravanthi Chidambaram, Fernando J. Velloso, Deborah E. Rothbard, Kaivalya Deshpande, Yvelande Cajuste, Kristin M. Snyder, Eduardo Fajardo, Andras Fiser, Nikos Tapinos, Steven W. Levison, Teresa L. Wood
Summary: The insulin receptor (INSR) plays a crucial role in maintaining adult neural stem cells (NSCs) and is also involved in brain tumor stem cell self-renewal. INSR deletion leads to a decrease in NSCs and an increase in progenitors, as well as hyposmia. Interestingly, hippocampal neurogenesis and behaviors remain unaffected. The high expression of INSR/insulin-like growth factor (IGF) pathway genes in aggressive glioblastomas suggests the importance of INSR in tumor stem cells.
Article
Anesthesiology
Jean Marcel de Mello, Pamela Vieira Andrade, Joilson Moura Santos, Acary Souza Bulle Oliveira, Mariz Vainzof, Luiz Gomes do Amaral, Helga Cristina Almeida da Silva
Summary: This study aimed to assess variables correlated with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. The results showed that IVCT results were correlated with clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering 0.2g contracture, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation).
BRAZILIAN JOURNAL OF ANESTHESIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Juliana Gurgel-Giannetti, Lucas Santos Souza, Guilherme L. Yamamoto, Marina Belisario, Monize Lazar, Wilson Campos, Rita de Cassia M. Pavanello, Mayana Zatz, Umbertina Reed, Edmar Zanoteli, Acary Bulle Oliveira, Vilma-Lotta Lehtokari, Erasmo B. Casella, Marcela C. Machado-Costa, Carina Wallgren-Pettersson, Nigel G. Laing, Vincenzo Nigro, Mariz Vainzof
Summary: Nemaline myopathy in Brazilian patients shows significant clinical and genetic heterogeneity, with a high frequency of NEB gene mutations. There is noticeable variability in clinical presentation and MRI patterns, with respiratory involvement often being severe.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Genetics & Heredity
Matheus Correia Casotti, Debora Dummer Meira, Alexia Stefani Siqueira Zetum, Bruno Cancian de Araujo, Danielle Ribeiro Campos da Silva, Eldamaria de Vargas Wolfgramm dos Santos, Fernanda Mariano Garcia, Flavia de Paula, Gabriel Mendonca Santana, Luana Santos Louro, Lyvia Neves Rebello Alves, Raquel Furlani Rocon Braga, Raquel Silva dos Reis Trabach, Sara Santos Bernardes, Thomas Erik Santos Louro, Eduardo Cremonese Filippi Chiela, Guido Lenz, Elizeu Fagundes de Carvalho, Iuri Drumond Louro
Summary: Precision and organization are important factors governing the cell cycle and ensuring normal cell proliferation. However, some cells may undergo abnormal cell divisions or variations of mitotic cycles, leading to the formation of polyploid giant cancer cells (PGCCs). These cells play a critical role in tumor survival, resistance, and immortalization, and can access multiple programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal. This literature review aims to explore the current knowledge about polyploidy in tumors, the applications of computational studies in understanding cancer polyploidy, and the contributions of PGCCs to tumorigenesis.
Review
Genetics & Heredity
Matheus Correia Casotti, Debora Dummer Meira, Lyvia Neves Rebello Alves, Barbara Gomes de Oliveira Bessa, Camilly Victoria Campanharo, Creuza Rachel Vicente, Carla Carvalho Aguiar, Daniel de Almeida Duque, Debora Goncalves Barbosa, Eldamaria de Vargas Wolfgramm dos Santos, Fernanda Mariano Garcia, Flavia de Paula, Gabriel Mendonca Santana, Isabele Pagani Pavan, Luana Santos Louro, Raquel Furlani Rocon Braga, Raquel Silva dos Reis Trabach, Thomas Santos Louro, Elizeu Fagundes de Carvalho, Iuri Drumond Louro
Summary: Translational Bioinformatics (TBI) is the combination of translational medicine and bioinformatics, which covers the entire spectrum from basic database discoveries to clinical applications and facilitates the transfer of scientific evidence to clinical practice.
Article
Cell Biology
Nayane dos Santos Brito Silva, Andreia da Silva Souza, Heloisa de Souza Andrade, Raphaela Neto Pereira, Camila Ferreira Bannwart Castro, Nicolas Vince, Sophie Limou, Michel Satya Naslavsky, Mayana Zatz, Yeda Aparecida de Oliveira Duarte, Celso Teixeira Mendes-Junior, Erick da Cruz Castelli
Summary: HLA-B is a highly variable gene in the human genome, encoding a key molecule for antigen presentation and immune cell modulation. However, previous studies focused mainly on coding regions, and the variability of introns and regulatory regions remains underexplored. In this study, a bioinformatics pipeline was used to assess HLA-B variability in a large population sample, revealing a high number of variable sites and geographically structured haplotype distribution. The findings suggest that HLA-B gene diversity is influenced by both population admixture and regional differences. This resource can enhance HLA imputation accuracy and advance our understanding of HLA-B genetic diversity in human populations.
Article
Genetics & Heredity
Pamela V. Andrade, Joilson M. Santos, Anne C. B. Teixeira, Vanessa F. Sogari, Michelle S. Almeida, Fabiano M. Callegari, Ana C. V. Krepischi, Acary S. B. Oliveira, Mariz Vainzof, Helga C. A. Silva
Summary: In this report, an 18-year-old male patient with a cervical nodule was found to have rhabdomyosarcoma in the ethmoidal sinus. The patient's positive in vitro contracture test for malignant hyperthermia (MH) and the presence of cores in muscle histopathological analysis suggest a possible association between rhabdomyosarcomas and MH susceptibility in patients with RYR1 variants. Molecular analysis further identified germline variants in the RYR1 and ASPSCR1 genes.
Article
Materials Science, Biomaterials
Tatiana Fontelonga, Arielle J. Hall, Jaedon L. Brown, Youngsook L. Jung, Matthew S. Alexander, Janice A. Dominov, Vincent Mouly, Natassia Vieira, Mayana Zatz, Mariz Vainzof, Emanuela Gussoni
Summary: Tetraspanin CD82 is a cell surface marker that binds dysferlin and myoferlin in muscle cells. Its expression is decreased in certain muscle dystrophy patients, indicating a potential role in muscle differentiation. This study provides new insights into the function of CD82 in skeletal muscle.
Article
Multidisciplinary Sciences
Amanda Faria Assoni, Thiago Giove Mitsugi, Rene Wardenaar, Raiane Oliveira Ferreira, Elisa Helena Farias Jandrey, Gabriela Machado Novaes, Isabela Fonseca de Oliveira Granha, Petra Bakker, Carolini Kaid, Mayana Zatz, Floris Foijer, Oswaldo Keith Okamoto
Summary: This study found that high expression of VAPB in medulloblastoma is associated with decreased patient survival, and VAPB is required for normal proliferation of medulloblastoma cells.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Venceslas Douillard, Nayane dos Santos Brito Silva, Sonia Bourguiba-Hachemi, Michel S. Naslavsky, Marilia O. Scliar, Yeda A. O. Duarte, Mayana Zatz, Maria Rita Passos-Bueno, Sophie Limou, Pierre-Antoine Gourraud, Elise Launay, Erick C. Castelli, Nicolas Vince
Summary: Human genomics has advanced rapidly, driving genome-wide association studies (GWASs). However, SNP-based GWASs are limited in capturing the polymorphism of HLA genes. This study evaluated the accuracy of using the 1000 Genomes data as a reference panel to impute HLA genotypes in admixed individuals and highlighted the importance of using genetically specific models for imputation.
Article
Biochemical Research Methods
Fernando Janczur Velloso, Ekta Kumari, Krista D. Buono, Michelle J. Frondelli, Steven W. Levison
Summary: This ex vivo approach uses EdU incorporation and multicolor flow cytometry to identify and quantify proliferating neural stem cells and progenitors in the mouse subventricular zone. It has been optimized for wild-type neonatal mice but is applicable to mice of any postnatal age.