We have employed upstream open reading frames (uORFs) to systematically tune the translation levels of recombinant proteins. We present the design principles that guided the development of this technology and provide information that may help others in implementing synthetic uORFs for their own applications. We also report on recent applications to our own research projects, including the coupling of uORF and translation initiation site (TIS) engineering with small molecule-inducible post-translational control. Finally, we discuss opportunities to investigate and potentially engineer gene-specific translational responses to cellular stress.
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http://dx.doi.org/10.4161/bioe.27607 | DOI Listing |
Biol Psychiatry Glob Open Sci
January 2025
Department of Psychiatry, New York University Grossman School of Medicine, New York, New York.
Background: An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.
Methods: We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels.
Environ Sci Atmos
December 2024
Instituto de Investigaciones en Ecosistemas y Sustentabilidad, Universidad Nacional Autónoma de México (UNAM) Morelia Michoacán 58190 Mexico.
The impact of cooking with solid fuels on neighborhood-scale PM concentrations in rural towns and communities is poorly quantified due to the lack of credible ground-level monitoring sites and spatial heterogeneity at a scale that is below the resolution of remote sensing GEOS-Chem hybrid models. Emissions of PM from use of open fires for cooking in rural Mexico are known to cause poor indoor air quality. The effectiveness of different intervention strategies to reduce such pollution exposures also varies because of different local building densities and source intensities.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied.
View Article and Find Full Text PDFCureus
November 2024
Gastroenterology, Barts Health NHS Trust, London, GBR.
Ulcerative colitis (UC) is a chronic immune-mediated intestinal condition. This case report describes an 82-year-old woman who was newly diagnosed with UC. Two years prior, she had multiple admissions for abdominal pain and rectal bleeding, initially diagnosed as diverticulitis.
View Article and Find Full Text PDFJ Interv Card Electrophysiol
December 2024
Department of Cardiovascular Medicine, Heart, Vascular & Thoracic Institute, Cleveland, USA.
Background: Despite advances in ablation and other therapies for AF, progression of atrial fibrillation (AF) remains a significant clinical problem, associated with worse prognosis and worse treatment outcomes. Upstream therapies targeting inflammatory or antifibrotic mechanisms have been disappointing in preventing AF progression, but more recently genetic and genomic studies in AF suggest novel cellular and metabolic stress targets, supporting prior studies of lifestyle and risk factor modification (LRFM) for AF. However, while obesity is a significant risk factor, weight loss and risk factor modification have not been successfully applied in a US population with AF.
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