Article
Virology
Vanessa Cristine de Souza Carneiro, Soniza Vieira Alves-Leon, Dmitry Jose de Santana Sarmento, Wagner Luis da Costa Nunes Pimentel Coelho, Otacilio da Cruz Moreira, Andreza Lemos Salvio, Carlos Henrique Ferreira Ramos, Carlos Henrique Ferreira Ramos Filho, Carla Augusta Barreto Marques, Joao Paulo da Costa Goncalves, Luciane Almeida Amado Leon, Vanessa Salete de Paula
Summary: This study found a high prevalence of herpesvirus in patients with COVID-19, and coinfection of SARS-CoV-2 and HHV was associated with neurological symptoms, but not with poorer outcomes.
Review
Medicine, General & Internal
Tina D. Jeppesen, Karen L. Madsen, Nanna S. Poulsen, Nicoline Lokken, John Vissing
Summary: Mutations in mtDNA disrupt energy production and cause varied symptoms. Exercise intolerance is a common symptom in mitochondrial myopathy, and exercise tests can be used for diagnosis and follow-up.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Clinical Neurology
Andreas Thimm, Alexander Carpinteiro, Sara Oubari, Maria Papathanasiou, Peter Luedike, Lukas Kessler, Christoph Rischpler, Tobias Blau, Hans Christian Reinhardt, Tienush Rassaf, Hartmut Schmidt, Christoph Kleinschnitz, Tim Hagenacker
Summary: Neurological involvement is common in systemic AL amyloidosis, particularly in the peripheral nervous system. Male sex and cardiac involvement are independent predictors of peripheral neuropathy. Peripheral neuropathy has no impact on survival.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Review
Cell Biology
Angelika Tkaczyk-Wlizlo, Krzysztof Kowal, Brygida Slaska
Summary: Currently, the problems caused by mitochondrial DNA (mtDNA) defects in mitochondrial diseases are often overlooked and genetic research tends to focus on nuclear genome (nDNA) alterations instead. However, for energy-dependent diseases, understanding the relationship between bioenergetic pathophysiology and mtDNA changes is critical. This paper aims to emphasize the role of mitochondrial and mtDNA defects in the development and progression of various diseases in dogs, highlighting the importance and consequences of mitochondrial genome alterations.
Article
Clinical Neurology
Olivia V. Poole, Chiara Pizzamiglio, David Murphy, Micol Falabella, William L. Macken, Enrico Bugiardini, Cathy E. Woodward, Robyn Labrum, Stephanie Efthymiou, Vincenzo Salpietro, Viorica Chelban, Rauan Kaiyrzhanov, Reza Maroofian, Anthony A. Amato, Allison Gregory, Susan J. Hayflick, Hallgeir Jonvik, Nicholas Wood, Henry Houlden, Jana Vandrovcova, Michael G. Hanna, Alan Pittman, Robert D. S. Pitceathly
Summary: The expanding catalog of neurogenetic disorders has led to a shift towards early clinical whole exome sequencing (WES). By reanalyzing exomes enriched with neurological diseases, pathogenic mtDNA variants were identified which resulted in diagnostic improvements in neurological diseases.
ANNALS OF NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Qianqian Zhuang, Fengfeng Guo, Lei Fu, Yufei Dong, Shaofang Xie, Xue Ding, Shuangyi Hu, Xuanhao D. Zhou, Yangwei Jiang, Hui Zhou, Yue Qiu, Zhaoying Lei, Mengyao Li, Huajian Cai, Mingjie Fan, Lingjie Sang, Yong Fu, Dong Zhang, Aifu Lin, Xu Li, Tilo Kunath, Ruhong Zhou, Ping Liang, Zhong Liu, Qingfeng Yan
Summary: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young individuals. In this study, a compound called 1-Deoxynojirimycin (DNJ) was found to rescue mitochondrial function in HCM cells by promoting the oligomerization of optic atrophy protein 1 (OPA1) and reconstructing the mitochondrial cristae. DNJ also improved the physiological properties of HCM cells and alleviated cardiac hypertrophy in a mouse model. These findings provide insights into the mechanism of HCM and offer a potential therapeutic strategy.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Hakan Alici, Vladimir N. Uversky, David E. Kang, Junga Alexa Woo, Orkid Coskuner-Weber
Summary: The mitochondria are responsible for energy production within the cell, and defects in this process can lead to mitochondrial myopathy. The CHCHD10 gene codes for a protein involved in mitochondrial function, and a specific mutation known as G58R has been found to disrupt its normal function and contribute to mitochondrial dysfunction and the development of mitochondrial myopathy. This study used modeling and simulations to explore the structural characteristics and impacts of the G58R mutation on CHCHD10(WT). The findings provide insights into the structural differences and effects of the G58R mutation, which could contribute to the development of new treatments for mitochondrial myopathy.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Urology & Nephrology
Minchao Cai, Qing Yu, Jinfang Bao
Summary: This case report highlights the occurrence of membranous nephropathy in a patient with mitochondrial myopathy, which has not been reported before. The findings suggest that renal manifestations should be carefully monitored in patients with mitochondrial mutations.
Article
Clinical Neurology
Kevin A. Strauss, Vincent J. Carson, Emilienne Bolettieri, Mariah Everett, Ashton Bollinger, Lauren E. Bowser, Keturah Beiler, Millie Young, Simon Edvardson, Nitay Fraenkel, Adele D'Amico, Enrico Bertini, Lokesh Lingappa, Devyani Chowdhury, Linda P. Lowes, Megan Iammarino, Lindsay N. Alfano, Karlla W. Brigatti
Summary: This study used WiTNNess as a hybrid prospective/cross-sectional observational study to simulate a clinical trial for infantile-onset TNNT1 myopathy. The results showed that WiTNNess established a sound operational framework for future clinical trials.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Mario K. Shammas, Xiaoping Huang, Beverly P. Wu, Evelyn Fessler, Insung Y. Song, Nicholas P. Randolph, Yan Li, Christopher K. E. Bleck, Danielle A. Springer, Carl Fratter, Ines A. Barbosa, Andrew F. Powers, Pedro M. Quiros, Carlos Lopez-Otin, Lucas T. Jae, Joanna Poulton, Derek P. Narendra
Summary: Mitochondrial stress triggers responses in both cellular mitochondria and nucleus. This study focuses on the impact of a mutation in the mitochondrial protein CHCHD10, which causes myopathy. The study finds that the mutated CHCHD10 aggregates in affected tissues, causing toxic stress on the inner mitochondrial membrane. The research also reveals the crucial role of the mitochondrial metalloendopeptidase OMA1 in coordinating stress responses and reshaping the mitochondrial network and proteome.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Luca Bosco, Daniela Leone, Laura Costa Comellas, Mauro Monforte, Marika Pane, Eugenio Mercuri, Enrico Bertini, Adele D'Amico, Fabiana Fattori
Summary: This study identified a novel MTM1 gene variant in a three-month-old child with XLMTM, which affects the normal splicing process. The researchers expanded the genotypic spectrum of XLMTM and highlighted the importance of sequencing intron-exon boundaries in male patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Anish Nikhanj, Jesi Bautista, Zaeem A. Siddiqi, Cecile L. Phan, Gavin Y. Oudit
Summary: Patients with mitochondrial diseases can develop cardiomyopathy, but the expression and penetrance of the disease vary. In this prospective study, a cohort of 53 patients with various mitochondrial diseases was evaluated, and a low prevalence of heart disease and a wide range of phenotypic variability were observed. Cardiovascular risk factors and aging were identified as important comorbidities in this patient population.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2022)
Review
Infectious Diseases
Jane Jackie David, Syed Ahmed Zaki, Preeti Shanbag
Summary: Human immunodeficiency virus type 1 (HIV-1) causes a range of diseases and neurological manifestations are common, contributing to morbidity and mortality. Recent evidence shows CNS involvement in HIV from initial viral entry, challenging the previous belief that it only affects the advanced stages of the disease. Neurological disorders in HIV-infected children can share similarities with adults, but there are also unique manifestations. Advances in treatment have led to more HIV-infected children surviving into adulthood, prompting the need to study primary neurologic disorders in this population.
JOURNAL OF INFECTION IN DEVELOPING COUNTRIES
(2023)
Article
Genetics & Heredity
Antoine Pegat, Nathalie Streichenberger, Nicolas Lacoste, Marc Hermier, Rita Menassa, Laurent Coudert, Julian Theuriet, Roseline Froissart, Sophie Terrone, Francoise Bouhour, Laurence Michel-Calemard, Laurent Schaeffer, Arnaud Jacquier
Summary: X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene. This paper describes a 22-year-old patient who developed XMEA at the age of 11, presenting with gait disorder and severe proximal weakness and amyotrophy in all four limbs. Muscle biopsy showed typical abnormalities of autophagic vacuolar myopathy. Genetic testing revealed a previously unreported intronic variant of the VMA21 gene, associated with altered splicing efficiency and intron retention.
Article
Genetics & Heredity
Yuqing Liu, Shuai Zhao, Xiaolei Chen, Yuehong Bian, Yongzhi Cao, Peiwen Xu, Changming Zhang, Jiangtao Zhang, Shigang Zhao, Han Zhao
Summary: This case-control study found an association between mtDNA variations and early embryonic development defects in infertile Chinese women, particularly in the d-loop region, ATP6 gene, and CYTB gene.
Article
Immunology
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H. Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A. Ashkar, Michel J. Tremblay, Dawn M. E. Bowdish, Charu Kaushic
CELLULAR & MOLECULAR IMMUNOLOGY
(2019)
Article
Biochemical Research Methods
S. Arthur Gilly, Lorraine Southam, Daniel Suveges, Karoline Kuchenbaecker, Rachel Moore, Giorgio E. M. Melloni, Konstantinos Hatzikotoulas, Aliki-Eleni Farmaki, Graham Ritchie, Jeremy Schwartzentruber, Petr Danecek, Britt Kilian, Martin O. Pollard, Xiangyu Ge, Emmanouil Tsafantakis, George Dedoussis, Eleftheria Zeggini
Article
Clinical Neurology
Andrea Accogli, Kether Guerrero, Maria Daniela D'Agostino, Luan Tran, Cecile Cieuta-Walti, Isabelle Thiffault, Sebastien Chenier, Jeremy Schwartzentruber, Jacek Majewski, Genevieve Bernard
JOURNAL OF CHILD NEUROLOGY
(2019)
Review
Biochemistry & Molecular Biology
Karim Sidhom, Patience O. Obi, Ayesha Saleem
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Maya Ghoussaini, Edward Mountjoy, Miguel Carmona, Gareth Peat, Ellen M. Schmidt, Andrew Hercules, Luca Fumis, Alfredo Miranda, Denise Carvalho-Silva, Annalisa Buniello, Tony Burdett, James Hayhurst, Jarrod Baker, Javier Ferrer, Asier Gonzalez-Uriarte, Simon Jupp, Mohd Anisul Karim, Gautier Koscielny, Sandra Machlitt-Northen, Cinzia Malangone, Zoe May Pendlington, Paola Roncaglia, Daniel Suveges, Daniel Wright, Olga Vrousgou, Eliseo Papa, Helen Parkinson, Jacqueline A. L. MacArthur, John A. Todd, Jeffrey C. Barrett, Jeremy Schwartzentruber, David G. Hulcoop, David Ochoa, Ellen M. McDonagh, Ian Dunham
Summary: Open Targets Genetics is an open-access integrative resource that aggregates human GWAS and functional genomics data to make connections between GWAS-associated loci and likely causal genes. Users can search, prioritize, and explore GWAS signals through data visualizations provided by the portal.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
David Ochoa, Andrew Hercules, Miguel Carmona, Daniel Suveges, Asier Gonzalez-Uriarte, Cinzia Malangone, Alfredo Miranda, Luca Fumis, Denise Carvalho-Silva, Michaela Spitzer, Jarrod Baker, Javier Ferrer, Arwa Raies, Olesya Razuvayevskaya, Adam Faulconbridge, Eirini Petsalaki, Prudence Mutowo, Sandra Machlitt-Northen, Gareth Peat, Elaine McAuley, Chuang Kee Ong, Edward Mountjoy, Maya Ghoussaini, Andrea Pierleoni, Eliseo Papa, Miguel Pignatelli, Gautier Koscielny, Mohd Karim, Jeremy Schwartzentruber, David G. Hulcoop, Ian Dunham, Ellen M. McDonagh
Summary: The Open Targets Platform provides a queryable knowledgebase and user interface for systematic target identification and prioritization for drug discovery, continuously improving evidence for target-disease relationships from various data sources. They have developed a new evidence scoring framework, added evaluation of post-marketing adverse drug reactions and target tractability, and optimized user interface and backend technologies to address the challenge of developing effective and safe drugs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Virology
Tushar Dhawan, Muhammad Atif Zahoor, Nishant Heryani, Samuel Tekeste Workenhe, Aisha Nazli, Charu Kaushic
Summary: HSV-2 primarily infects epithelial cells at skin and mucosal surfaces, and our study demonstrates that the host factor TRIM26 plays a crucial role in evasion of anti-viral response, leading to increased viral replication. Overexpression of TRIM26 enhances virus production, while knockout of TRIM26 results in minimal replication of HSV-2; TRIM26 KO cells exhibit significant upregulation of interferon-beta production and ISG expression both before and after HSV-2 infection.
Letter
Nutrition & Dietetics
Sarah M. Reyes, Kozeta Miliku, Deborah Chan, Meredith Brockway, Sarah Turner, Katherine A. Kearns, Christina Raimondi, Ayesha Saleem, Lauren E. Kelly, Nathan C. Nickel, Meghan B. Azad
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Immunology
Matthew William Woods, Muhammad Atif Zahoor, Jeffrey Lam, Puja Bagri, Haley Dupont, Chris P. Verschoor, Aisha Nazli, Charu Kaushic
Summary: The study found that MPA causes changes in gene expression in vaginal epithelial cells, increasing the expression of genes related to cholesterol/sterol synthesis while decreasing those related to cell division and cell-cell adhesion, which in turn reduces barrier integrity and increases susceptibility to HIV-1 infection.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2021)
Correction
Genetics & Heredity
Jeremy Schwartzentruber, Sarah Cooper, Jimmy Z. Liu, Inigo Barrio-Hernandez, Erica Bello, Natsuhiko Kumasaka, Adam M. H. Young, Robin J. M. Franklin, Toby Johnson, Karol Estrada, Daniel J. Gaffney, Pedro Beltrao, Andrew Bassett
Summary: A correction to this paper has been published, and more information can be found at the provided link.
Article
Genetics & Heredity
Jeremy Schwartzentruber, Sarah Cooper, Jimmy Z. Liu, Inigo Barrio-Hernandez, Erica Bello, Natsuhiko Kumasaka, Adam M. H. Young, Robin J. M. Franklin, Toby Johnson, Karol Estrada, Daniel J. Gaffney, Pedro Beltrao, Andrew Bassett
Summary: A genome-wide AD meta-analysis identified 37 risk loci, including new associations near CCDC6, TSPAN14, NCK2, and SPRED2. By fine-mapping SNPs and using functional annotation, 21 SNPs with >50% probability of being causally involved in AD risk were identified. Protein interaction networks and tissue-specific expression helped prioritize genes, leading to the discovery of likely causal genes.
Article
Genetics & Heredity
Adam M. H. Young, Natsuhiko Kumasaka, Fiona Calvert, Timothy R. Hammond, Andrew Knights, Nikolaos Panousis, Jun Sung Park, Jeremy Schwartzentruber, Jimmy Liu, Kousik Kundu, Michael Segel, Natalia A. Murphy, Christopher E. McMurran, Harry Bulstrode, Jason Correia, Karol P. Budohoski, Alexis Joannides, Mathew R. Guilfoyle, Rikin Trivedi, Ramez Kirollos, Robert Morris, Matthew R. Garnett, Ivan Timofeev, Ibrahim Jalloh, Katherine Holland, Richard Mannion, Richard Mair, Colin Watts, Stephen J. Price, Peter J. Kirkpatrick, Thomas Santarius, Edward Mountjoy, Maya Ghoussaini, Nicole Soranzo, Omer A. Bayraktar, Beth Stevens, Peter J. Hutchinson, Robin J. M. Franklin, Daniel J. Gaffney
Summary: By analyzing primary human microglia isolated from 141 patients undergoing neurosurgery, the study found how age, sex, clinical pathology, and genetic variants influence microglia gene expression. Using a macrophage model, a candidate causal variant for Alzheimer's disease at the BIN1 locus was fine-mapped. This research provides a population-scale transcriptional map of the important cell for human CNS development and disease.
Article
Genetics & Heredity
Edward Mountjoy, Ellen M. Schmidt, Miguel Carmona, Jeremy Schwartzentruber, Gareth Peat, Alfredo Miranda, Luca Fumis, James Hayhurst, Annalisa Buniello, Mohd Anisul Karim, Daniel Wright, Andrew Hercules, Eliseo Papa, Eric B. Fauman, Jeffrey C. Barrett, John A. Todd, David Ochoa, Ian Dunham, Maya Ghoussaini
Summary: In this study, an open resource was introduced to systematically fine map and prioritize genes across published GWAS loci, aiming at identifying causal genes associated with complex traits. By training a machine learning model using genetics and functional genomics data, the authors were able to distinguish causal genes from neighboring genes, outperforming distance-based models. The prioritized genes were found to be enriched for known approved drug targets, suggesting their potential in drug development.
Article
Biochemistry & Molecular Biology
Benjamin Bydak, Taiana M. Pierdona, Samira Seif, Karim Sidhom, Patience O. Obi, Hagar Labouta, Joseph W. Gordon, Ayesha Saleem
Summary: Extracellular vesicles (EVs) play a crucial role in cellular communication and can be influenced by exercise. This study investigated the characteristics of skeletal muscle-derived EVs and the effect of acute contractile activity. The results showed that EVs from myotubes were smaller and had higher protein yield compared to EVs from myoblasts. Acute stimulation did not affect the biophysical profile or protein markers in EVs. Further research is needed to explore the effects of chronic contractile activity on the biophysical characteristics and cargo of skeletal muscle-specific EVs.
Article
Biochemistry & Molecular Biology
Sarah E. Cooper, Jeremy Schwartzentruber, Erica Bello, Eve L. Coomber, Andrew R. Bassett
NUCLEIC ACIDS RESEARCH
(2020)