Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 () gene may contribute to the risk of Alzheimer's disease (AD). Currently, there is no consensus as to whether expression is up- or down-regulated in AD brains, hindering a clear interpretation of 's role in this disease. The aim of this study was to determine if RNA levels differ between AD and control brains. We applied RT-qPCR to study transcription in human postmortem brain (PMB) and assessed associations of these RNA levels with genetic variants in and We also compared RNA levels with mitochondrial functions in human cell lines. Initially, we found that the human genome carries multiple pseudogenes capable of producing highly homologous RNAs that can obscure precise RNA measurements. To circumvent this obstacle, we developed a novel RNA expression assay targeting the primary transcript of . Using this assay, we showed that RNA was upregulated in AD PMB. Additionally, elevated RNA levels were associated with decreases in mitochondrial DNA copy number and mitochondrial membrane potential in oxidative stress-challenged cells. Overall, differential transcription of RNA in the brain is associated with AD and could be an indicator of mitochondrial dysfunction.
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http://dx.doi.org/10.3390/genes12060871 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.
Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.
View Article and Find Full Text PDFPLoS One
January 2025
Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Preeclampsia is characterized by insufficient invasion of extravillous trophoblasts and is a consequence of failed adaption of extravillous trophoblasts to changes in the intrauterine environment developing embryo. Specific miRNAs are implicated in the development of preeclampsia (PE). miR-455-5p is present at low levels in PE but its role is not known.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.
Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.
Adv Sci (Weinh)
January 2025
Department of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Advanced Agriculture Sciences and School of Life Sciences, State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing, 100871, China.
In plants, microRNAs (miRNAs) participate in complex gene regulatory networks together with the transcription factors (TFs) in response to biotic and abiotic stresses. To date, analyses of miRNAs-induced transcriptome remodeling are at the whole plant or tissue levels. Here, Arabidopsis's ABA-induced single-cell RNA-seq (scRNA-seq) is performed at different stages of time points-early, middle, and late.
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