Article
Biochemistry & Molecular Biology
Yumi Tsuneura, Masahito Sawahata, Norimichi Itoh, Ryoya Miyajima, Daisuke Mori, Takao Kohno, Mitsuharu Hattori, Akira Sobue, Taku Nagai, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada
Summary: Reelin, a crucial extracellular matrix protein secreted by Cajal-Retzius cells, plays important roles in brain development and neuronal functions. Reductions in Reelin are associated with brain dysfunctions in mental disorders like schizophrenia. A recent study identified a novel deletion in RELN encoding Reelin in Japanese schizophrenia patients, leading to abnormalities in brain structures and social behavior.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Geriatrics & Gerontology
Matthew Bracher-Smith, Ganna Leonenko, Emily Baker, Karen Crawford, Andrew C. Graham, Dervis A. Salih, Brian W. Howell, John Hardy, Valentina Escott-Price
Summary: The study suggests that APOE-epsilon 4 carriers may have other genetic factors influencing the progression of Alzheimer's disease, with the discovery of a novel genome-wide significant locus associated to AD in the DAB1 gene. The analysis also indicates a potential epistatic interaction between the APOE locus and the DAB1-RELN pathway in AD.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Nataliya Di Donato, Renzo Guerrini, Charles J. Billington, A. James Barkovich, Philine Dinkel, Elena Freri, Michael Heide, Elliot S. Gershon, Tracy S. Gertler, Robert J. Hopkin, Suma Jacob, Sarah K. Keedy, Daniz Kooshavar, Paul J. Lockhart, Dietmar R. Lohmann, Iman G. Mahmoud, Elena Parrini, Evelin Schrock, Giulia Severi, Andrew E. Timms, Richard Webster, Mary J. H. Willis, Maha S. Zaki, Joseph G. Gleeson, Richard J. Leventer, William B. Dobyns
Summary: Reelin, encoded by the RELN gene, is critical for brain development and function. Variants in RELN have been associated with various neurodevelopmental disorders, including lissencephaly and potentially schizophrenia. This study provides data on individuals with biallelic and monoallelic RELN variants, expanding the spectrum of associated phenotypes.
Article
Engineering, Marine
Chieh Lun Liu, Erica A. Dasi, Aaron M. Watson, Allen R. Place, Rosemary Jagus
Summary: The present study investigates the response of cobia, a marine fish species, to stressors by measuring the phosphorylation of eIF2 alpha, a translational initiation factor. The study found that the phosphorylation state of eIF2 alpha in cobia is affected by factors such as diet, water temperature, and cellular nutrient deficiency. Additionally, the study suggests that evaluating eIF2 alpha phosphorylation could serve as an early marker for assessing diet, environmental stressors, and disease in cobia, which is particularly important for optimizing the rearing conditions of cobia larvae and juveniles.
JOURNAL OF MARINE SCIENCE AND ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Lu Wang, Xi Wang, Xiying Lv, Qiushuo Jin, Hongcai Shang, Chih-chen Wang, Lei Wang
Summary: Protein disulfide isomerase (PDI) plays a critical role in platelet aggregation, thrombosis, and hemostasis, and inhibiting PDI may be a novel antithrombotic strategy. The interaction between endoplasmic reticulum oxidoreductin-1 alpha (Ero1 alpha) and PDI in mediating platelet aggregation through an extracellular electron transport pathway is investigated. The study reveals that oxidized PDI promotes platelet aggregation, and Ero1 alpha regulates platelet aggregation in a glutathione-dependent manner.
Article
Biochemistry & Molecular Biology
Guillermo Lopez-Domenech, Jack H. Howden, Christian Covill-Cooke, Corinne Morfill, Jigna Patel, Roland Burli, Damian Crowther, Nicol Birsa, Nicholas J. Brandon, Josef T. Kittler
Summary: Research has shown that Miro proteins play a crucial role in mitochondrial turnover and dysfunction may contribute to neurodegenerative diseases. Genetic deletion or inhibition of Miro1 ubiquitination delays Parkin translocation to damaged mitochondria, leading to reduced mitochondrial clearance. Knockout of Miro1 in hippocampus and cortex results in disrupted mitophagy, enlarged mitochondria, and hyperactivation of the integrated stress response, potentially indicating a role in human neurodegenerative disease pathogenesis.
Article
Microbiology
Zhaolan Ding, Teresa M. Lamb, Ahmad Boukhris, Rachel Porter, Deborah Bell-Pedersen
Summary: In the model fungus Neurospora crassa, the circadian clock regulates rhythmic protein synthesis by controlling the phosphorylation and dephosphorylation of a conserved translation initiation factor, eIF2 alpha. This temporal coordination of phosphorylation and dephosphorylation events allows for the partitioning of translation to the night, which helps coordinate energy metabolism with protein synthesis and cellular growth.
Article
Endocrinology & Metabolism
Ben Ma, Yi Luo, Weibo Xu, Litao Han, Wanlin Liu, Tian Liao, Yichen Yang, Yu Wang
Summary: This study identified specific long noncoding RNAs (lncRNAs) associated with anaplastic thyroid cancer (ATC) and investigated their biological functions and molecular mechanisms in the regulation of malignancy in ATC. The findings suggest that LINC00886 could serve as a potential biomarker and therapeutic target for ATC. LINC00886 was found to negatively regulate cell proliferation, migration, and invasion in ATC, and its downregulation led to enhanced activity of eukaryotic initiation factor 2 alpha (eIF2α) and promoted protein synthesis to maintain ATC malignancy.
Article
Biochemistry & Molecular Biology
Zhongyan Wu, Fan Mei, Yangyang Gan, Anhang Liu, Jiapan Hu, Yan Jin, Yuxin Yin
Summary: This study shows that FAM69C promotes stress granule assembly through phosphorylation of eIF2 alpha. Knockout of Fam69c in microglia leads to aberrant stress granule assembly and neuroinflammation. The findings suggest that FAM69C plays a critical role in regulating microglia function and stress response.
Article
Cell Biology
Simon Lizarazo, Yeeun Yook, Nien-Pei Tsai
Summary: Alzheimer's disease is a common form of dementia, characterized by the accumulation of amyloid beta peptide. This study reveals that Fmr1 is involved in A beta-induced translational suppression, leading to hyposynchrony of neuronal firing activity and loss of excitatory synapses. The mechanism involves the repression of phosphatases by Fmr1, resulting in translational suppression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Veterinary Sciences
Ting Zhu, Xueli Jiang, Hangkuo Xin, Xiaohui Zheng, Xiaonuan Xue, Ji-Long Chen, Baomin Qi
Summary: PRV induces GADD34 expression to promote eIF2 alpha dephosphorylation, maintaining protein synthesis and facilitating viral replication.
VETERINARY RESEARCH
(2021)
Article
Environmental Sciences
Quanshu Wang, Wanqi Ma, Shuping Zhang
Summary: Cadmium is a toxic heavy metal pollutant that can cause anemia and metabolic disorders. Heme-regulated eIF2 alpha kinase (HRI) plays a crucial role in preventing anemia and toxicity in response to various stresses, including cadmium exposure. This study identified proteins associated with glycolysis that were upregulated after cadmium exposure in wild-type mice, but this induction was disrupted in Hri knockout mice, suggesting the involvement of HRI in cadmium-induced glycolysis. These findings provide insights into potential targets for metabolic disorders following acute cadmium exposure.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Medicine, Research & Experimental
Veronica A. Bahamondes Lorca, Bernardo D. Bastidas Mayorga, Lingying Tong, Shiyong Wu
Summary: This study revealed a novel mechanism explaining the sustained high levels of phosphorylated eIF2 alpha in HaCaT cells post-UVB, mainly through the inhibition of ATF4 and GADD34 translation.
Article
Cell Biology
Dorota Gil, Marta Zarzycka, Joanna Pabijan, Ma lgorzata Lekka, Joanna Duli Dulinska-Litewka
Summary: Melanoma is resistant to chemotherapy and lacks fully effective targeted therapies. The mutations in melanoma lead to the hyperactivation of the MAPK and PI3K/AKT/mTOR pathways, which are responsible for abnormal protein synthesis. In this study, we investigated the effects of a specific PI3K/mTOR inhibitor, dactolisib, and Mnk inhibitor -CGP57380, alone and in combination on human melanoma cell lines. Both drugs showed inhibition of cell proliferation and migration when used individually, but their combination had additional antitumor effects. Simultaneous inhibition of both pathways may help overcome drug resistance.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Xupeng Bai, Jie Ni, Julia Beretov, Valerie C. Wasinger, Shanping Wang, Ying Zhu, Peter Graham, Yong Li
Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype, and radiotherapy is an effective treatment option. However, acquired radioresistance is a major challenge. The integrated stress response (ISR) pathway is found to be highly activated in radioresistant TNBC cells, with the eIF2 alpha /ATF4 axis proposed as a potential therapeutic target.
Article
Sport Sciences
Steven D. Hicks, Paige Jacob, Omar Perez, Matthew Baffuto, Zofia Gagnon, Frank A. Middleton
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
(2019)
Article
Neurosciences
Kristen Swieck, Amanda Conta-Steencken, Frank A. Middleton, Justin R. Siebert, Donna J. Osterhout, Dennis J. Stelzner
Article
Psychology, Developmental
Steven D. Hicks, Randall L. Carpenter, Kayla E. Wagner, Rachel Pauley, Mark Barros, Cheryl Tierney-Aves, Sarah Barns, Cindy Dowd Greene, Frank A. Middleton
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
(2020)
Article
Cell Biology
Yaxin Liu, Xiaowen Wang, Liam P. Coyne, Yuan Yang, Yue Qi, Frank A. Middleton, Xin Jie Chen
MOLECULAR BIOLOGY OF THE CELL
(2019)
Article
Multidisciplinary Sciences
Aakriti Pandita, Poornima Ramadas, Aarati Poudel, Nibal Saad, Ankit Anand, Alina Basnet, Dongliang Wang, Frank Middleton, Diana M. Gilligan
Article
Multidisciplinary Sciences
Sanghee Lim, Nicole Hermance, Tenny Mudianto, Hatim M. Mustaly, Ian Paolo Morelos Mauricio, Marc A. Vittoria, Ryan J. Quinton, Brian W. Howell, Hauke Cornils, Amity L. Manning, Neil J. Ganem
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Rachel E. H. Sager, Adam K. Walker, Frank Middleton, Kate Robinson, Maree J. Webster, Cynthia Shannon Weickert
Summary: The immune system components play a role in regulating synapse formation and refinement in neurodevelopment. The complement pathway, associated with cell lysis and phagocytosis, is involved in synaptic elimination. Changes in complement activity during human development, particularly during adolescence, may be linked to the onset of neurodevelopmental disorders such as autism or schizophrenia.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Tohru Matsuki, Akio Iio, Masashi Ueda, Yumi Tsuneura, Brian W. Howell, Atsuo Nakayama
Summary: Precise control of neuronal migration is crucial for the laminar organization of the neocortex and overall brain function. MST3 can compensate for the loss of Stk25 and rescue deficits in neuronal migration and abnormal axonogenesis. STK25 activates Rac1 and reduces RhoA levels, both of which are essential for restoring proper neuronal migration in the brain.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Education, Special
David Levitskiy, Alexandra Confair, Kayla E. Wagner, Samantha DeVita, Nicole Shea, Elizabeth P. McKernan, Justin Kopec, Natalie Russo, Frank A. Middleton, Steven D. Hicks
Summary: This study identified specific salivary RNAs associated with ASD behaviors in older individuals and found that these RNAs changed as early as three months after therapy initiation in younger children. These findings suggest that salivary RNAs could be potential biomarkers for tracking treatment effectiveness and prognosis in ASD. Further validation is needed to confirm these results.
RESEARCH IN AUTISM SPECTRUM DISORDERS
(2021)
Article
Clinical Neurology
Miriam Sartages, Mar Garcia-Colomer, Cristina Iglesias, Brian W. Howell, Manuel Macia, Patricia Pena, Celia M. Pombo, Juan Zalvide
Summary: The CCM3-associated kinases STK24 and STK25 play a major role in the inhibition of cavernoma development. Deficiency in these kinases leads to aggressive vascular lesions and vascular anomalies.
Article
Gastroenterology & Hepatology
Yeshwant Kurhe, Mara Caputo, Emmelie Cansby, Ying Xia, Sima Kumari, Sumit Kumar Anand, Brian W. Howell, Hanns-Ulrich Marschall, Margit Mahlapuu
Summary: The study indicates that antagonizing STK25 signaling inhibits the development of NASH-related HCC, suggesting further analysis of STK25 as a therapeutic target for NASH-induced HCC treatment.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
David A. Larsen, Mary B. Collins, Qian Du, Dustin Hill, Tabassum Z. Insaf, Pruthvi Kilaru, Brittany L. Kmush, Frank Middleton, Abigail Stamm, Maxwell L. Wilder, Teng Zeng, Hyatt Green
Summary: Wastewater surveillance is a rapid method to estimate population-level disease transmission and predict the probability of SARS-CoV-2 transmission in a community. A study in upstate New York found that the intensity of SARS-CoV-2 in wastewater correlated with COVID-19 incidence and test positivity, and when SARS-CoV-2 was not detected in wastewater, there were fewer reported COVID-19 cases.
Article
Psychology, Developmental
Kayla E. Wagner, Jennifer B. McCormick, Sarah Barns, Molly Carney, Frank A. Middleton, Steven D. Hicks
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2020)
Article
Public, Environmental & Occupational Health
Christina D. Lupone, Danielle Daniels, Dawn Lammert, Robyn Borsuk, Travis Hobart, Sandra Lane, Andrea Shaw
JOURNAL OF IMMIGRANT AND MINORITY HEALTH
(2020)
Article
Psychology, Clinical
Richard E. Mattson, Nicole Cameron, Frank A. Middleton, Lisa R. Starr, Joanne Davila, Matthew D. Johnson
JOURNAL OF FAMILY PSYCHOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)