The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions. In budding yeast, regions of silent chromatin, such as those at telomeres and mating-type loci, cluster at the nuclear envelope creating zones that favour gene repression. Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes. Here we report that transcriptional activation of a subtelomeric gene, HXK1 (hexokinase isoenzyme 1), by growth on a non-glucose carbon source led to its relocalization to nuclear pores. This relocation required the 3' untranslated region (UTR), which is essential for efficient messenger RNA processing and export, consistent with an accompanying report. However, activation of HXK1 by an alternative pathway based on the transactivator VP16 moved the locus away from the nuclear periphery and abrogated the normal induction of HXK1 by galactose. Notably, when we interfered with HXK1 localization by either antagonizing or promoting association with the pore, transcript levels were reduced or enhanced, respectively. From this we conclude that nuclear position has an active role in determining optimal gene expression levels.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/nature04845 | DOI Listing |
J Fluoresc
January 2025
Department of Fine Chemistry, Seoul National University of Science and Technology, Seoul, 01811, Korea.
We report a bithiophene-based fluorescence probe BDT (2,2'-(((1 E, 1'E)-[2,2'-bithiophene]-5,5'-diylbis(methaneylylidene))bis(azaneylylidene))bis(4-(tert-butyl)phenol)) for recognizing ClO. BDT selectively responded to ClO, leading to a blue fluorescence enhancement in a mixture of DMF/HEPES buffer (9:1, v/v). Importantly, BDT showed an ultrafast response (within 1 s) to ClO among the fluorescent turn-on chemosensors based on bithiophene.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Purpose: Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now.
View Article and Find Full Text PDFJACC Cardiovasc Imaging
January 2025
National Amyloidosis Centre, University College London, Royal Free Campus, Rowland Hill Street, London, United Kingdom.
Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.
View Article and Find Full Text PDFJACC Cardiovasc Imaging
January 2025
Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.
Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.
JACC Clin Electrophysiol
December 2024
Physiology, Amsterdam Cardiovascular Sciences, Heart Failure, and Arrhythmias, Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:
Background: Atrial fibrillation (AF) persistence is associated with molecular remodeling that fuels electrical conduction abnormalities in atrial tissue. Previous research revealed DNA damage as a molecular driver of AF.
Objectives: This study sought to explore the diagnostic value of DNA damage in atrial tissue and blood samples as an indicator of the prevalence of electrical conduction abnormalities and stage of AF.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!