Article
Neurosciences
Karissa Barthelson, Stephen Martin Pederson, Morgan Newman, Michael Lardelli
Summary: The study using zebrafish as a model organism found that EOfAD-like mutations in SORL1 affect mitochondrial and ribosomal function, independent of changes in the expression of A beta PP-related proteins.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Shannon Chiang, Nady Braidy, Sanaz Maleki, Sean Lal, Des R. Richardson, Michael L. -H. Huang
Summary: This study investigated mitochondrial homeostasis in Friedreich's ataxia (FA) cardiomyopathy, revealing significant changes in key mitochondrial homeostatic mechanisms in the hearts of frataxin-deficient mice. The findings demonstrated dysfunction in mitochondrial proliferation, NAD+ metabolism, and mitochondrial dynamics, with an accumulation of Pink1/Parkin and increased autophagic/mitophagic flux. This mechanistic dissection offers insights into potential treatments targeting mitochondrial homeostasis and NAD+ metabolism in FA and other cardiodegenerative diseases.
Review
Biochemistry & Molecular Biology
Yuhan Zhang, Mengying Chen, Caiyong Chen
Summary: Vertebrates generate mature red blood cells through a highly regulated, multistep process called erythropoiesis. Defects in erythropoiesis can lead to various blood disorders, and the molecular mechanisms are conserved between fish and mammals. Zebrafish has served as a powerful genetic model for studying erythropoiesis, providing important insights into RBC development and establishing models for human blood diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Jose Maria Moreno-Navarrete, Jose Manuel Fernandez-Real
Summary: Iron regulation is crucial for maintaining healthy adipose tissue function. Excessive accumulation of iron in adipose tissue can lead to dysfunction. Understanding the interplay between iron and adipose tissue is important for developing new therapeutic approaches to improve and prevent adipose tissue dysfunction.
Article
Physiology
Ruiqin Hu, Genfang Li, Qianghua Xu, Liangbiao Chen
Summary: This study investigated the role of iron in the hypoxic responses of two zebrafish-derived cell lines. The results showed that iron homeostasis is important for maintaining mitochondrial integrity in hypoxic stress, and this effect is cell type-dependent.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Wanye Hu, Chaoting Zhou, Qiangan Jing, Yancun Li, Jing Yang, Chen Yang, Luyang Wang, Jiayu Hu, Huanjuan Li, Hairui Wang, Chen Yuan, Yi Zhou, Xueying Ren, Xiangmin Tong, Jing Du, Ying Wang
Summary: The study found that FTH is upregulated in multiple cancers such as LIHC, CHOL, HNSC compared to corresponding normal tissues. Serum ferritin levels are positively associated with the progression of hepatitis, cirrhosis, and hepatocellular carcinoma. FTH expression correlates with tumor grades, cancer stages, and prognosis of HCC.
CANCER CELL INTERNATIONAL
(2021)
Article
Plant Sciences
Joaquin Vargas, Isabel Gomez, Elena A. Vidal, Chun Pong Lee, A. Harvey Millar, Xavier Jordana, Hannetz Roschzttardtz
Summary: Iron is a crucial micronutrient for plants, especially in mitochondrial electron transfer reactions. In this study, the role of Mitochondrial Iron Transporters (MIT) in Arabidopsis thaliana was investigated. It was found that single mutant plants for either AtMIT1 or AtMIT2 showed no phenotypic defects, but when the double mutant Atmit1 Atmit2 was created, multiple developmental defects were observed. RNA-Seq analysis revealed differential expression of over 760 genes, including those involved in iron transport, coumarin metabolism, hormone metabolism, root development, and stress response. Furthermore, a phenomenon of T-DNA suppression and mitochondrial perturbation was observed in the second generation of Atmit1 Atmit2 double mutant plants. Finally, targeted proteomic analysis showed that a protein level of 30% of MIT2 is sufficient for normal plant growth under iron-sufficient conditions.
Article
Genetics & Heredity
Min-Kyung Nam, Jeong-Mi Moon, Goo-Young Kim, Sung Min Kim, Hyangshuk Rhim
Summary: This study identified zebrafish HtrA2 as the true counterpart of human HtrA2, shedding light on its role in regulating cell survival and death. The zebrafish-zHtrA2 system provides a valuable tool to study the important role of HtrA2 and develop novel therapeutics for HtrA2-associated diseases.
Article
Multidisciplinary Sciences
Fengxiu Sun, Zhenzhen Zhao, Mathilda M. Willoughby, Shuaiqi Shen, Yu Zhou, Yiyan Shao, Jing Kang, Yongtian Chen, Mengying Chen, Xiaojing Yuan, Iqbal Hamza, Amit R. Reddi, Caiyong Chen
Summary: This study identifies HRG-9 as an intracellular haem chaperone that plays a crucial role in transporting haem within cells. Loss of HRG-9 leads to haem accumulation in different cellular compartments and is associated with symptoms resembling certain genetic disorders.
Article
Biochemistry & Molecular Biology
Jinjiang Fan, Vassilios Papadopoulos
Summary: Deletion of the TSPO gene in MA-10 cells results in reduced mitochondrial membrane potential and significant changes in nuclear gene expression. This is likely due to dysregulation of several signaling pathways, including those involved in regulating membrane potential, calcium signaling, extracellular matrix, and phagocytosis. The compensatory response to loss of TSPO involves changes in expression of transcription factors, such as key members of the NF-kappa B pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Theresa S. Rimmele, Shaomin Li, Jens Velde Andersen, Emil W. Westi, Alexander Rotenberg, Jianlin Wang, Blanca Irene Aldana, Dennis J. Selkoe, Chiye J. Aoki, Chris G. Dulla, Paul Allen Rosenberg
Summary: The major glutamate transporter GLT-1 is expressed in both presynaptic terminals and astrocytes in the mammalian central nervous system. While astrocytic GLT-1 is believed to primarily regulate glutamate homeostasis, the function of neuronal GLT-1 has remained relatively unexplored. Conditional knockout of GLT-1 in neurons resulted in impaired stimulus-evoked field extracellular postsynaptic potentials (fEPSPs), suggesting a crucial role for neuronal GLT-1 in excitatory synaptic transmission. Excitotoxicity may underlie the transmission failure observed in neuronal GLT-1 knockout mice, with potential metabolic perturbations contributing to vulnerability to NMDA receptor activation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Neurosciences
Zehui Li, Yu Cao, Hui Pei, Lina Ma, Yang Yang, Hao Li
Summary: Alzheimer's disease is the most common neurodegenerative disease without effective treatments. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are associated with AD pathogenesis, but there is a lack of literature summarizing recent advances. This article reviews the roles of MAM structure and tethering proteins in the pathogenesis of AD and potential treatment strategies targeting MAMs.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Catherine R. Wasser, Gordon C. Werthmann, Eric M. Hall, Kristina Kuhbandner, Connie H. Wong, Murat S. Durakoglugil, Joachim Herz
Summary: This study demonstrates the role of alternative splicing and release of Apoer2-ICD in regulating translating transcripts in the mouse hippocampus. Dysregulated Apoer2 splicing may contribute to synaptic deficits and neurodegeneration in Alzheimer's disease. These findings suggest the Reelin/Apoer2 pathway as a potential target for AD therapeutics.
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Andrew B. Caldwell, Qing Liu, Can Zhang, Gary P. Schroth, Douglas R. Galasko, Kevin D. Rynearson, Rudolph E. Tanzi, Shauna H. Yuan, Steven L. Wagner, Shankar Subramaniam
Summary: This study characterized the endotypes associated with Alzheimer's disease through RNA-seq analysis of neurons derived from early-onset Alzheimer's patients. The identified endotypes were used as evaluation metrics for screening gamma secretase drugs. The results showed that the drug treatment could partially restore neuronal state and improve the disease by influencing cell cycle and cell differentiation.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Karissa Barthelson, Yang Dong, Morgan Newman, Michael Lardelli
Summary: Analysis of brain transcriptomes in young adult zebrafish revealed both similarities and differences in the effects of heterozygosity for psen1 mutations causing EOfAD or fAI. The contrasting effects observed may shed light on how these mutation types lead to distinct diseases.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Karissa Barthelson, Stephen Martin Pederson, Morgan Newman, Michael Lardelli
Summary: The study using zebrafish as a model organism found that EOfAD-like mutations in SORL1 affect mitochondrial and ribosomal function, independent of changes in the expression of A beta PP-related proteins.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Karissa Barthelson, Morgan Newman, Cameron J. Nowell, Michael Lardelli
Summary: The study found that the increased basal expression of hypoxia responsive genes in the brains of zebrafish with psen1 mutations is not due to changes in vascular morphology.
Article
Zoology
Stephen C. Donnellan, Sarah R. Catalano, Stephen Pederson, Kieren J. Mitchell, Aidan Suhendran, Luke C. Price, Paul Doughty, Stephen J. Richards
Summary: The study reveals that the Wotjulum frog comprises two deeply divergent mitochondrial DNA lineages, showing differences in shape but not in color and pattern. The two taxa exhibit substantial differences in female biased sexual size dimorphism.
Article
Biotechnology & Applied Microbiology
Yang Dong, Morgan Newman, Stephen M. Pederson, Karissa Barthelson, Nhi Hin, Michael Lardelli
Summary: Early-onset familial Alzheimer’s disease (EOfAD) is driven by dominant mutations, where studies in zebrafish models have identified potential effects on mitochondrial function, endolysosomal acidification, DNA replication, cell cycle, and iron ion transport associated with specific mutations. These effects may underlie the pathogenic mechanisms of EOfAD and provide potential targets for therapeutic interventions.
Review
Genetics & Heredity
Ning Liu, Wai Yee Low, Hamid Alinejad-Rokny, Stephen Pederson, Timothy Sadlon, Simon Barry, James Breen
Summary: Eukaryotic genomes are highly organized within the cell nucleus, allowing for interactions between regulatory elements and gene promoters in three-dimensional space. Hi-C methodology has enabled the analysis of genome interactions, focusing on potentially functional interactions through structural-based discovery, statistically significant chromatin interactions, and epigenomic data integration. Careful use of these approaches is crucial for successful identification of potentially functional interactions within the genome.
EPIGENETICS & CHROMATIN
(2021)
Article
Biochemistry & Molecular Biology
Konstantinos J. Bogias, Stephen M. Pederson, Shalem Leemaqz, Melanie D. Smith, Dale McAninch, Tanja Jankovic-Karasoulos, Dylan McCullough, Qianhui Wan, Tina Bianco-Miotto, James Breen, Claire T. Roberts
Summary: This study profiles transcript expression profiles in human placental tissue samples and finds that early placental development is mainly regulated by differential transcript expression (DTE) rather than differential gene expression (DGE). Transcript usage is likely a regulatory mechanism in early placentation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Ning Liu, Timothy Sadlon, Ying Y. Wong, Stephen Pederson, James Breen, Simon C. Barry
Summary: Using 3DFAACTS-SNP, we identified 36 SNPs with plausible Treg-specific mechanisms of action from a list of 1228 previously fine-mapped variants. Integration of cell type-specific chromosome conformation capture data in 3DFAACTS-SNP identified 266 regulatory regions and 47 candidate target genes that interact with these variant-containing regions in Treg cells. The workflow was further applied to three other SNP autoimmune datasets, identifying 16 Treg-centric candidate variants and 60 interacting genes.
EPIGENETICS & CHROMATIN
(2022)
Article
Multidisciplinary Sciences
Aaron E. Casey, Wenjun Liu, Leanne K. Hein, Timothy J. Sargeant, Stephen M. Pederson, Ville-Petteri Makinen
Summary: Autophagy is an intracellular recycling process that degrades harmful molecules and enables cell survival during starvation. This study utilizes a systems biology approach to identify differentially expressed genes and disease pathways associated with autophagy, providing potential targets for further research on neurodegenerative diseases.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Ellen G. Jarred, Zhipeng Qu, Tesha Tsai, Ruby Oberin, Sigrid Petautschnig, Heidi Bildsoe, Stephen Pederson, Qing-hua Zhang, Jessica M. Stringer, John Carroll, David K. Gardner, Maarten van den Buuse, Natalie A. Sims, William T. Gibson, David L. Adelson, Patrick S. Western
Summary: This study identifies a specific period of early oocyte growth in which PRC2 is expressed in mouse oocytes, deletion of Eed during this window leads to the de-repression of 343 genes. Many of these de-repressed genes are developmental regulators and the majority are not imprinted genes. The findings indicate that EED has spatially and temporally distinct functions in the female germline to repress a wide range of developmentally important genes, and this activity is conserved in the mouse and human germlines.
CLINICAL EPIGENETICS
(2022)
Article
Immunology
Caitlin A. Abbott, Emily L. Freimayer, Timona S. Tyllis, Todd S. Norton, Mohammed Alshari, Aaron H. S. Heng, Stephen M. Pederson, Zhipeng Qu, Mark Armstrong, Geoffrey R. Hill, Shaun R. Mccoll, Iain Comerford
Summary: During the resolution of IAV infection in mice, FOXP3-IL-10+CD4+ T cells transiently accumulate in the lung and contribute to immune suppression. These cells can be divided into four populations based on the expression of LAG-3 and CD49b, and each population exhibits suppressive potential consistent with the definition of Tr1 cells.
MUCOSAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Ying Y. Wong, Jessica E. Harbison, Christopher M. Hope, Batjargal Gundsambuu, Katherine A. Brown, Soon W. Wong, Cheryl Y. Brown, Jennifer J. Couper, Jimmy Breen, Ning Liu, Stephen M. Pederson, Maren Koehne, Kathrin Klee, Joachim Schultze, Marc Beyer, Timothy Sadlon, Simon C. Barry
Summary: ATAC-seq allows profiling of chromatin accessibility and gene expression in cryopreserved rare cell populations, providing insights into epigenetic features and transcriptional regulation in health and disease.
SCIENTIFIC REPORTS
(2023)
Article
Cell & Tissue Engineering
J. Sung, K. R. Barratt, S. M. Pederson, C. Chenu, I. Reichert, G. J. Atkins, P. H. Anderson, P. J. Smitham
Summary: This study found that impaired fracture healing in patients with type 2 diabetes mellitus (T2DM) may be due to elevated or prolonged inflammation. Gene expression analysis revealed several upregulated genes associated with inflammation in the fracture callus of T2DM rats. These identified genes may serve as biomarkers for monitoring and treating delayed fracture healing in diabetic patients.
BONE & JOINT RESEARCH
(2023)
Article
Neurosciences
Karissa Barthelson, Stephen Martin Pederson, Morgan Newman, Haowei Jiang, Michael Lardelli
Summary: Studying mutations in the zebrafish psen2 gene, both frameshift and in-frame mutations cause discrete effects, with in-frame mutation impacting genes related to oxidative phosphorylation, long-term potentiation, and the cell cycle, while frameshift mutation affecting Notch and MAPK signaling, extracellular matrix receptor interactions, and focal adhesion. Both mutations influence ribosomal protein gene expression but in opposite directions.
JOURNAL OF ALZHEIMERS DISEASE REPORTS
(2021)