Review
Biochemistry & Molecular Biology
Elizaveta A. A. Olkhova, Laura A. A. Smith, Carla Bradshaw, Grainne S. Gorman, Daniel Erskine, Yi Shiau Ng
Summary: Mitochondrial diseases are common genetic neurometabolic disorders that currently lack effective therapies. This review discusses various mouse models with transgenic impairments in genes regulating mitochondrial function, focusing on their neurological phenotype and neuropathological features. Most mouse models exhibit ataxia, similar to patients, and share the neuropathological finding of Purkinje neuron loss. However, none of the existing models fully recapitulate the severe neurological phenotypes seen in patients, such as refractory focal seizures and stroke-like episodes. The roles of reactive astrogliosis and microglial reactivity in driving neuropathology, as well as alternative mechanisms of cellular death in neurons during mitochondrial bioenergy crisis, are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Maria Likhatcheva, Roben G. Gieling, James A. L. Brown, Constantinos Demonacos, Kaye J. Williams
Summary: Genotoxic stress can activate the ATM kinase, with potential involvement of Suv39H1 and Tip60 in ATM activation under hypoxic conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sapir Schlam-Babayov, Ariel Bensimon, Michal Harel, Tamar Geiger, Ruedi Aebersold, Yael Ziv, Yosef Shiloh
Summary: This study conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells to reveal the fine-tuned dynamics and relationships between PIKKs in the response to genotoxic stress. The results highlight the complex interactions among ATM, ATR, and DNA-PK in the DDR.
Article
Immunology
Ruth Pia Duecker, Lucia Gronau, Patrick C. Baer, Stefan Zielen, Ralf Schubert
Summary: Our study focused on investigating the feasibility of different approaches of hematopoietic stem cell transplantation (HSCT) for Ataxia-telangiectasia (A-T) by using Atm-deficient mice as models. The results showed that haploidentical HSCT could extend the lifespan of Atm-deficient mice and improve T-cell numbers and functionality. Interestingly, HSCT using heterozygous donor cells also led to improved survival and enhanced CD4 cell functionality in Atm-deficient mice, suggesting it as a potential strategy for A-T treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Clinical Neurology
Marius Theis, Helena Donath, Sandra Woelke, Shahrzad Bakhtiar, Emilia Salzmann-Manrique, Stefan Zielen, Matthias Kieslich
Summary: This study aimed to evaluate peripheral neurodegeneration and age-dependent neuropathy development in A-T patients through neurophysiological measurements. The findings revealed that neuropathic changes can be observed as early as the first year of life in A-T patients, although subjective symptoms are rarely reported. Motor neuropathy in the upper extremities was predominantly of a demyelinating type, while sensory neuropathy was predominantly of a mixed type. In the lower extremities, both motor and sensory neuropathy were predominantly of a mixed type. Age was found to have a significant correlation with the development of motor and sensory polyneuropathy in A-T patients compared to healthy controls.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biology
Harvey Perez, May F. Abdallah, Jose Chavira, Angelina S. Norris, Martin T. Egeland, Karen L. Vo, Callan L. Buechsenschuetz, Valentina Sanghez, Jeannie L. Kim, Molly Pind, Kotoka Nakamura, Geoffrey G. Hicks, Richard A. Gatti, Joaquin Madrenas, Michelina Iacovino, Peter J. McKinnon, Paul J. Mathews
Summary: By introducing null mutations in both the Atm and Aptx genes in mice, researchers have created a novel mouse model that exhibits progressively severe ataxic phenotype and cerebellar molecular layer atrophy. The perturbations significantly alter the biophysical properties of cerebellar Purkinje neurons and their neural activity, correlating with cerebellar atrophy and ataxia over the animal's first year of life. Additionally, the double mutant mice also show a predisposition to cancer and immune abnormalities, resembling symptoms of A-T.
Article
Multidisciplinary Sciences
Changwei Chen, Jennifer R. Gallagher, Jamie Tarlton, Lidy van Aalten, Susan E. Bray, Michael L. J. Ashford, Rory J. McCrimmon, Ewan R. Pearson, Alison D. McNeilly, Calum Sutherland
Summary: Genotype may influence the therapeutic effects of metformin for type-2 diabetes, and the NPAT gene may play a role in the mechanism of metformin action.
Article
Clinical Neurology
Matej Skorvanek, Robert Jech, Juliane Winkelmann, Michael Zech
Summary: A male patient with immunodeficiency of unknown etiology since childhood developed a medication-refractory choreodystonic movement disorder at the age of 42. Exome-wide molecular testing revealed a pathogenic variant in the CD40LG gene, confirming the existence of a CD40LG-related condition combining compromised immunity with neurodegenerative movement abnormalities. Establishing the diagnosis is crucial due to potential life-threatening immunological complications.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Cell Biology
Aifang Cheng, Kai-Hei Tse, Hei-Man Chow, Yunqiao Gan, Xuan Song, Fulin Ma, Yi Xuan Yvonne Qian, Weiyi She, Karl Herrup
Summary: ATM protein is associated with cellular organelles such as synaptic vesicles, endosomes, and lysosomes, with its deficiency impacting autophagy and lysosomal function in neurons. This disruption leads to impaired neuronal functions including synaptic maintenance, neuronal survival, and glucose uptake.
Article
Medical Laboratory Technology
Chunyu Gu, Hong Wang, Jianbo Shu, Jie Zheng, Dong Li, Chunquan Cai, Peiyuan Zhang
Summary: This study described atypical symptoms of A-T in a 5-year-old girl and proposed a dual-omics diagnostic approach combining RNA-seq with WES. The study also discussed phenotypic heterogeneity of A-T among family members and individuals.
CLINICA CHIMICA ACTA
(2021)
Article
Immunology
Maria Giovanna Desimio, Andrea Finocchi, Gigliola Di Matteo, Silvia Di Cesare, Carmela Giancotta, Francesca Conti, Luciana Chessa, Maria Piane, Davide Montin, Marta Dellepiane, Paolo Rossi, Caterina Cancrini, Margherita Doria
Summary: NK cells in A-T patients show reduced NKG2D expression, possibly contributing to increased susceptibility. The abnormal expression of NKG2D in A-T patients may be associated with disease progression.
CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Yousra Ajouaou, Elena Magnani, Bhavani Madakashira, Eleanor Jenkins, Kirsten C. Sadler
Summary: Research on zebrafish demonstrates that overexpression of the UHRF1 gene causes a small liver, while mutation of the Atm gene exacerbates this phenomenon. It is also found that oxidative stress is one of the causes of the small liver, and the Atm gene can alleviate the effects of this stress.
Article
Multidisciplinary Sciences
Rudel A. Saunders, Thomas F. Michniacki, Courtney Hames, Hilary A. Moale, Carol Wilke, Molly E. Kuo, Johnathan Nguyen, Andrea J. Hartlerode, Bethany B. Moore, JoAnn M. Sekiguchi
Summary: Ataxia-telangiectasia (A-T) is a multisystem disorder with lung complications as a major cause of mortality. This study demonstrates the significant role of ATM-deficient immune cells in causing lung pathologies in A-T, and suggests that targeted inhibition of aberrant inflammatory responses could be a viable therapeutic strategy for A-T lung disease.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Zhongjun Du, Shangya Chen, Guanqun Cui, Ye Yang, Enguo Zhang, Qiang Wang, Martin F. Lavin, Abrey J. Yeo, Cunxiang Bo, Yu Zhang, Chao Li, Xiaoshan Liu, Xu Yang, Cheng Peng, Hua Shao
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2019)
Article
Oncology
Michael J. McKay, Jeffery Craig, Paul Kalitsis, Sergei Kozlov, Sandra Verschoor, Phillip Chen, Pavel Lobachevsky, Raja Vasireddy, Yuqian Yan, Jacinta Ryan, George McGillivray, Ravi Savarirayan, Martin F. Lavin, Robert G. Ramsay, Huiling Xu
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2019)
Article
Oncology
Yi Chieh Lim, Kathleen S. Ensbey, Carolin Offenhauser, Rochelle C. J. D'souza, Jason K. Cullen, Brett W. Stringer, Hazel Quek, Zara C. Bruce, Amanda Kijas, Valentina Cianfanelli, Bijan Mahboubi, Fiona Smith, Rosalind L. Jeffree, Lisa Wiesmueeller, Adrian P. Wiegmans, Amanda Bain, Fanny J. Lombard, Tara L. Roberts, Kum Kum Khanna, Martin F. Lavin, Baek Kim, Petra Hamerlik, Terrance G. Johns, Mark J. Coster, Andrew W. Boyd, Bryan W. Day
Review
Immunology
Parisa Amirifar, Reza Yazdani, Tannaz Moeini Shad, Alireza Ghanadan, Hassan Abolhassani, Martin Lavin, Soheila Sotoudeh, Asghar Aghamohammadi
IMMUNOLOGICAL INVESTIGATIONS
(2020)
Article
Forestry
Franklin Alongi, Andrew J. Hansen, David Laufenberg, Robert E. Keane, Kristin Legg, Matt Lavin
Article
Biochemistry & Molecular Biology
Lea Voelkening, Anna Vatselia, Girmay Asgedom, Holger Bastians, Martin Lavin, Detlev Schindler, Axel Schambach, Kristine Bousset, Thilo Doerk
Article
Biochemistry & Molecular Biology
Dmitry A. Ovchinnikov, Sarah L. Withey, Hannah C. Leeson, U. Wang Lei, Ashmitha Sundarrajan, Keerat Junday, Michelle Pewarchuk, Abrey J. Yeo, Amanda W. Kijas, Martin F. Lavin, Ernst J. Wolvetang
HUMAN MOLECULAR GENETICS
(2020)
Review
Biotechnology & Applied Microbiology
Martin F. Lavin, Abrey J. Yeo
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2020)
Article
Integrative & Complementary Medicine
Jin He, Ru Han, Gongchang Yu, Martin Francis Lavin, Qiang Jia, Ping Cui, Cheng Peng
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2020)
Article
Ecology
Jens J. Ringelberg, Niklaus E. Zimmermann, Andrea Weeks, Matt Lavin, Colin E. Hughes
GLOBAL ECOLOGY AND BIOGEOGRAPHY
(2020)
Article
Cell Biology
Goutham Narayanan Subramanian, Jessica Greaneyle, Zhe Wei, Olivier Becherel, Martin Lavin, Hayden Anthony Homer
JOURNAL OF CELL BIOLOGY
(2020)
Article
Agronomy
Norman F. Weeden, Clarice J. Coyne, Matthew Lavin, Kevin McPhee
Summary: The study revealed high genetic diversity in the STAYGREEN gene of the Pisum genus, which is crucial for distinguishing between different varieties, understanding the relationship between wild and commercial species. Additionally, the gene showed a fast evolutionary rate, with the formation of indels contributing to the observed high level of variation.
GENETIC RESOURCES AND CROP EVOLUTION
(2021)
Article
Forestry
Andrew J. Hansen, Alyson East, Robert E. Keane, Matt Lavin, Kristin Legg, Zachary Holden, Chris Toney, Franklin Alongi
Summary: The study found that smaller diameter whitebark pine trees were not proportionally more abundant at lower elevations, suggesting that competitive exclusion may not be the primary mechanism limiting this species' distribution at lower elevations. However, smaller diameter whitebark pine trees were slightly less warm-dry tolerant than larger individuals, indicating a shift in the regeneration zone towards higher elevations possibly due to warming in the Greater Yellowstone Ecosystem. The predicted zone of suitable habitat for smaller diameter whitebark pine trees was 122 meters lower in elevation compared to reproductive-sized trees in previous studies, implying that the species may be slightly less sensitive to climate warming but could still face range contractions in the future.
FOREST ECOLOGY AND MANAGEMENT
(2021)
Article
Plant Sciences
Jordan Meyer-Morey, Matthew Lavin, Jane Mangold, Catherine Zabinski, Lisa J. Rew
Summary: The use of indaziflam to control nonnative annual mustards was effective, but had negative impacts on the diversity and richness of the diverse mountain sagebrush steppe plant communities within Yellowstone National Park, particularly affecting the native annual forbs. Further evaluation of the herbicide's effects on the nontarget community is recommended.
INVASIVE PLANT SCIENCE AND MANAGEMENT
(2021)
Article
Multidisciplinary Sciences
David Kazadi, Junghyun Lim, Gerson Rothschild, Veronika Grinstein, Brice Laffleur, Olivier Becherel, Martin J. Lavin, Uttiya Basu
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.