Article
Endocrinology & Metabolism
Matthew Devall, Darren M. Soanes, Adam R. Smith, Emma L. Dempster, Rebecca G. Smith, Joe Burrage, Artemis Iatrou, Eilis Hannon, Claire Troakes, Karen Moore, Paul O'Neill, Safa Al-Sarraj, Leonard Schalkwyk, Jonathan Mill, Michael Weedon, Katie Lunnon
Summary: This study presents a novel approach to investigate the patterns of mitochondrial DNA methylation in human brain tissue. The results show relatively low but conserved patterns of mitochondrial DNA methylation, with peaks observed in the D-LOOP and several genes in a non-CpG context. Differential methylation patterns associated with age, sex, and brain region were also identified. This study provides detailed annotation of DNA methylation in the mitochondrial genome and highlights the potential role of mitochondrial epigenetic mechanisms in disorders characterized by mitochondrial dysfunction.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Analytical
Zi-yue Wang, Huimin Yuan, Dong-ling Li, Juan Hu, Jian-Ge Qiu, Chun-yang Zhang
Summary: In this study, a ligation-mediated nanosensor was developed for sensitive quantification of 5hmC modification in cancer cells. The nanosensor showed excellent specificity and high amplification efficiency, and could detect as low as 0.001% 5hmC DNA in complex mixtures. It also had the ability to monitor cellular 5hmC level and distinguish cancer cells from normal cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Medicine, General & Internal
Xin-Xin Yan, Na Guo, Song-Wei Ru, Zhi-Yuan Wang, Hai-Juan Sui, Yin-Shi Xu, Zhen-Dan Yao
Summary: The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. This study aimed to identify the predictors of colon cancer prognosis by detecting the levels of 5mC, 5hmC, 5fC, and 5caC in colon cancer and adjacent non-tumor tissues. The results showed that 5mC and 5hmC can serve as biomarkers for colon cancer and are stable predictors and therapeutic targets.
Article
Multidisciplinary Sciences
Ramya Viswanathan, Elsie Cheruba, Pui-Mun Wong, Yao Yi, Shaun Ngang, Dawn Qingqing Chong, Yuin-Han Loh, Iain Beehuat Tan, Lih Feng Cheow
Summary: In this study, the researchers developed a new method called DARESOME that allows simultaneous measurement of 5mC and 5hmC modifications in DNA, particularly in samples with limited quantities. By applying DARESOME, they revealed the roles of 5mC and 5hmC in gene regulation and aging, as well as discovered cancer signatures in liquid biopsy.
Review
Oncology
Bo Xu, Hao Wang, Li Tan
Summary: Both genetic and epigenetic mechanisms contribute to breast cancer pathogenesis. Aberrant 5mC oxidation and dysregulated TET family genes are associated with diseases, including breast cancer, playing critical roles in various physiological and pathophysiological processes. The impacts of these alterations have been extensively investigated in the past decade.
Article
Developmental Biology
Pooja Sagvekar, Gayatri Shinde, Vijay Mangoli, Sadhana K. Desai, Srabani Mukherjee
Summary: This study identifies alterations in DNA methylation and demethylation levels in cumulus granulosa cells (CGCs) of women with polycystic ovary syndrome (PCOS), and demonstrates a correlation between these alterations and the expression levels of DNA methylating and demethylating enzymes. These findings suggest that the development of PCOS may be linked to intrinsic changes in the transcriptional regulation of these enzymes.
MOLECULAR HUMAN REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Adelaida Hernaiz, Sara Sentre, Marina Betancor, Oscar Lopez-Perez, Monica Salinas-Pena, Pilar Zaragoza, Juan Jose Badiola, Janne Markus Toivonen, Rosa Bolea, Inmaculada Martin-Burriel
Summary: Scrapie is a transmissible spongiform encephalopathy characterized by the presence of the abnormal prion protein PrPSc. This study investigates the involvement of DNA methylation in scrapie pathogenesis by analyzing the levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in infected brain tissues of sheep and mice. The results show a decrease in 5mC levels and opposite patterns of 5hmC between the two models. Additionally, expression analysis of epigenetic regulatory genes reveals differences between the disease models. These findings support the role of DNA methylation and associated enzymes in the neurodegenerative course of prion diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Jiadong Chi, Wei Zhang, Yigong Li, Jie Zhao, Xiangqian Zheng, Ming Gao
Summary: This study found that abnormal 5hmC expression is closely related to the malignancy of thyroid cancer, while TET3 has differential expression in thyroid cancer and can promote cancer cell proliferation, migration and invasion.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
William A. Pastor, Sin Young Kwon
Summary: The placenta has a unique methylome compared to somatic cell types, featuring low DNA methylation, partially methylated domains, and methylation of CpG islands important in somatic development. Similar phenomena are observed in human cancers, suggesting similarities between placental epigenome formation and cancer. The placenta also has an expanded set of imprinted genes formed through distinctive developmental pathways. Recent discoveries shed light on how the unusual placental epigenetic state may arise, but key questions remain unresolved.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Analytical
Yan Sun, Stephanie Stransky, Jennifer Aguilan, Sanjay Koul, Scott J. Garforth, Michael Brenowitz, Simone Sidoli
Summary: A new direct injection mass spectrometry (DI-MS) platform is introduced for accurate, precise, and fast quantitation of DNA cytidine methylation and hydroxymethylation. The platform offers high sensitivity and throughput, overcoming biases in chromatographic retention and sample degradation.
ANALYTICA CHIMICA ACTA
(2021)
Review
Horticulture
Aamir Ali Shaikh, Sadaruddin Chachar, Muzafaruddin Chachar, Nazir Ahmed, Changfei Guan, Pingxian Zhang
Summary: Traditional plant breeding involves crossing and selection based on morphological traits, while phenotypic selection has been supplemented by molecular methods. Genome editing with techniques like CRISPR-Cas9 is a novel approach for directly modifying crop nucleotide sequences. Understanding epigenetic variations, such as DNA methylation, has also provided opportunities for crop improvement.
Article
Biology
Anabelle Planques, Pierre Kerner, Laure Ferry, Christoph Grunau, Eve Gazave, Michel Vervoort
Summary: High levels of 5mC methylation were found in the annelid P. dumerilii, indicating that this feature is not specific to vertebrates in the bilaterian clade. The dynamic nature of 5mC methylation levels in P. dumerilii throughout its life cycle suggests a potential role in development and regeneration processes.
Article
Virology
Claudia E. Oropeza, Grant Tarnow, Taha Y. Taha, Rasha E. Shalaby, Marieta V. Hyde, Mark Maienschein-Cline, Stefan J. Green, Alan McLachlan
Summary: Research indicates that HBV biosynthesis increases during early postnatal liver development, correlating with the loss of DNA methylation. Increased activity of FoxA and Tet is associated with HBV gene expression, while decreased Dnmt leads to demethylation of HBV DNA.
JOURNAL OF VIROLOGY
(2021)
Article
Oncology
Hang-Yu Chen, Wei-Long Zhang, Lei Zhang, Ping Yang, Fang Li, Ze-Ruo Yang, Jing Wang, Meng Pang, Yun Hong, Changjian Yan, Wei Li, Jia Liu, Nuo Xu, Long Chen, Xiu-Bing Xiao, Yan Qin, Xiao-Hui He, Hui Liu, Hai-Chuan Zhu, Chuan He, Jian Lin, Hong-Mei Jing
Summary: This study identified thirteen 5hmC markers associated with treatment response in DLBCL patients. The logistic regression model showed superior prediction performance compared to existing clinical indicators, such as LDH and stage. The findings suggest that 5hmC modifications in cfDNA before R-CHOP treatment are linked to treatment response and may serve as a minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.
CLINICAL EPIGENETICS
(2021)
Article
Oncology
Nasim Azizgolshani, Curtis L. Petersen, Youdinghuan Chen, Joshua J. Levy, Lucas A. Salas, Laurent Perreard, Lananh N. Nguyen, Brock C. Christensen
Summary: This study focused on nucleotide-specific 5hmC in pediatric central nervous system tumors, revealing that tumors generally exhibit lower levels of 5hmC throughout the epigenome. The research also demonstrated that tumor 5hmC is localized to key regulatory elements involved in cell identity. Furthermore, differences in hydroxymethylated loci among tumor subtypes were found to be hypermethylated and disproportionately located in CTCF binding sites and genes related to posttranscriptional RNA regulation. Additionally, patients with low 5hmC patterns showed poorer overall survival and higher risk of recurrence.
CLINICAL EPIGENETICS
(2021)
Article
Biochemistry & Molecular Biology
Marcus S. Dyer, Laura A. Reale, Katherine E. Lewis, Adam K. Walker, Tracey C. Dickson, Adele Woodhouse, Catherine A. Blizzard
Summary: ALS is a chronic neurodegenerative disease characterized by mislocalisation of the TDP-43 protein from the nucleus to the cytoplasm. Research in mouse models indicates that mislocalised TDP-43 causes intrinsic hyperexcitability and synaptic dysfunction in motor cortex neurons.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Cell Biology
Rachel Atkinson, Jacqueline Leung, James Bender, Matthew Kirkcaldie, James Vickers, Anna King
Summary: Mislocalization of TDP-43 protein in mouse retinal ganglion cells led to alterations in neurofilament expression and a decrease in neurofilament-positive axons in the optic nerve, accompanied by increased microglial density. Furthermore, TDP-43 mislocalization was associated with increased pre-synaptic input into retinal ganglion cells.
DISEASE MODELS & MECHANISMS
(2021)
Article
Neurosciences
Rachel A. K. Atkinson, Hannah L. Fair, Richard Wilson, James C. Vickers, Anna E. King
Summary: The study found that overexpression of TDP-43 in neurons increased the abundance of actin-binding proteins, leading to changes in neurite branching and growth cone morphology. These results provide further insights into the role of TDP-43 in regulating the cytoskeleton and neuronal development.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)
Review
Cell Biology
Gongbu Pan, Anna King, Feitong Wu, Steve Simpson-Yap, Adele Woodhouse, Andrew Phipps, James C. Vickers
Summary: Alzheimer's disease (AD) is a complex neurological disorder with uncertain etiology, influenced by both genetic factors and lifestyle. Despite decades of genetic research, much of the heritability of AD remains unexplained, suggesting potential associations with rare variants, gene-environment interactions, and epigenetic factors. Aging is a significant risk factor for AD, but longitudinal studies on the association of genetic factors with cognitive decline and preclinical stages are limited.
AGEING RESEARCH REVIEWS
(2021)
Article
Geriatrics & Gerontology
Hoang Nguyen, Kathleen Veronica Doherty, Claire E. A. Eccleston, Aidan Bindoff, Laura Tierney, Ron Mason, Andrew Robinson, James Vickers, Fran McInerney
Summary: The CAAASI-Dem is a valid and reliable tool for assessing dementia literacy. The study demonstrated good internal reliability, convergent validity, and the ability to discriminate between groups with different levels of care experience. Recommendations for future research and practice are provided.
AGING & MENTAL HEALTH
(2022)
Article
Ethics
Frederic Gilbert, John Noel M. Viana, Merlin Bittlinger, Ian Stevens, Maree Farrow, James Vickers, Susan Dodds, Judy Illes
Summary: The increasing trend of invasive neural trials for people with dementia globally is highlighted, with significant heterogeneity in enrolment criteria that urgently requires review and refinement; balancing risks and potential benefits while ensuring capacity for informed consent is crucial in testing novel therapeutic approaches.
Article
Behavioral Sciences
Edward Hill, Jane Alty, Larissa Bartlett, Lyn Goldberg, Mira Park, Soonja Yeom, James Vickers
Summary: Analyzing propositional idea density (PID) through autobiographical writing tasks and computer tools can help detect language deficits early, especially in elderly individuals. Although the effect sizes were small, PID may serve as a highly sensitive measure for quantifying language deficits.
Article
Clinical Neurology
J. Morgan, A. Bindoff, K. Doherty, J. Vickers, J. Alty
Summary: A study found that future doctors are not adequately prepared to prevent dementia, as they have limited ability in recognizing dementia risk factors, especially vascular risk factors. Although their general knowledge of dementia is satisfactory, their understanding of modifiable risk factors for dementia is limited.
JOURNAL OF CLINICAL NEUROSCIENCE
(2022)
Article
Environmental Sciences
Yun-Hee Jeon, Mirim Shin, Adam Smith, Elizabeth Beattie, Henry Brodaty, Dennis Frost, Anthony Hobbs, Piers Kotting, Glenys Petrie, Martin Rossor, Jane Thompson, James Vickers, Donna Waters
Summary: Recruiting participants for dementia research can be time-consuming, but using the digital platform StepUp for Dementia Research can improve recruitment efficiency and user satisfaction. The platform provides a secure way for volunteers to register and allows researchers to access volunteers more easily.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Multidisciplinary Sciences
Andrew Keniry, Natasha Jansz, Linden J. Gearing, Iromi Wanigasuriya, Joseph Chen, Christian M. Nefzger, Peter F. Hickey, Quentin Gouil, Joy Liu, Kelsey A. Breslin, Megan Iminitoff, Tamara Beck, Andres Tapia del Fierro, Lachlan Whitehead, Andrew Jarratt, Sarah A. Kinkel, Phillippa C. Taberlay, Tracy Willson, Miha Pakusch, Matthew E. Ritchie, Douglas J. Hilton, Jose M. Polo, Marnie E. Blewitt
Summary: In this study, a replenishable female mouse embryonic stem cell system was developed to study X chromosome inactivation (XCI). Through a targeted genetic screen, the researchers identified the BAF complex as essential for creating nucleosome-depleted regions at promoters on the inactive X chromosome during the early stages of XCI establishment. This model system provides a valuable tool for discovering unknown factors involved in XCI and epigenetic silencing.
NATURE COMMUNICATIONS
(2022)
Article
Geriatrics & Gerontology
B. Fulopova, W. Bennett, B. S. Summers, K. E. Stuart, A. E. King, J. C. Vickers, A. J. Canty
Summary: This study focused on the structural properties of en passant boutons (EPBs) in Alzheimer's disease, finding that EPBs showed resilience and maintained a stable synaptic density across all experimental conditions, despite a significant reduction in the dynamic fraction of APP/PS1 axons at 10-13 months of age.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Xinyi Wang, Rebecca J. St George, Aidan D. Bindoff, Alastair J. Noyce, Katherine Lawler, Eddy Roccati, Larissa Bartlett, Son N. Tran, James C. Vickers, Quan Bai, Jane Alty
Summary: This study found that online keyboard tapping tests can predict cognitive abilities, particularly episodic memory. These tests provide a low-cost method for early detection of Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)
Review
Biochemistry & Molecular Biology
Sophie M. Navickas, Katherine A. Giles, Kate H. Brettingham-Moore, Phillippa C. Taberlay
Summary: The chromatin remodeler SMARCA4/BRG1 plays a key role in brain tumour development, with its function varying in different tumour types and subtypes. Altered SMARCA4 expression is associated with various brain tumours, and mutations primarily occur in the catalytic ATPase domain, which has tumour suppressor activity. However, SMARCA4 can also promote tumourigenesis through overexpression. This review explores the complex interaction between SMARCA4 and different brain cancer types, highlighting its role in tumour pathogenesis, regulated pathways, and advances in understanding the functional relevance of mutations. The potential of targeting SMARCA4 as adjuvant therapy to enhance current brain cancer treatment methods is also discussed.
Article
Clinical Neurology
Larissa Bartlett, James J. R. Brady, Maree Farrow, Sarang Kim, Aidan Bindoff, Hannah Fair, James C. Vickers, Duncan Sinclair
Summary: A study comparing data from before and during the first COVID-19 lockdown in Tasmania, Australia did not show widespread negative effects on modifiable dementia risk factors. Despite slight contraction in friend networks during lockdown, there were no detrimental effects observed.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2021)
Article
Neurosciences
Barbora Fulopova, Kimberley E. Stuart, William Bennett, Aidan Bindoff, Anna E. King, James C. Vickers, Alison J. Canty
Summary: The prefrontal cortex is more susceptible to Aβ deposition and less responsive to the effects of environmental enrichment, while the primary motor cortex and somatosensory cortex reach a plateau in Aβ deposition by 12 months and are more susceptible to modification by midlife environmental enrichment.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
