To test the hypothesis that the asymmetry in the afferent traffic of the intra-right atrium (RA) ATP-triggered vagal reflex is due to the stimulation by ATP of extrapulmonary (i.e., cardiac) vagal chemosensitive afferent terminals, ATP, adenosine, and capsaicin were given into the canine RA and the aortic root (AR; n = 12); ATP and adenosine were also administered into the left common carotid artery and the descending aorta (n = 6). The negative chronotropic action [i.e., suppression of sinus node (SN) automaticity] of the test compounds and time to peak effect (tp) were determined. Under baseline conditions, ATP given into the left common carotid artery had a relatively very small effect. ATP given into the descending aorta had no effect. In contrast, intra-RA and intra-AR ATP markedly suppressed SN automaticity, the former less than the latter; the opposite was true for capsaicin. Intra-RA adenosine was much less potent than intra-RA ATP. The tp of intra-RA ATP and intra-RA adenosine were larger than the tp of intra-AR ATP. Pulmonary denervation did not alter the effects of intra-RAATP, intra-ARATP, or intra-AR capsaicin but almost abolished the effect of intra-RA capsaicin. Subsequent bilateral, but not left, cervical vagotomy markedly reduce the effects of ATP and eliminated the difference between the effects of ATP and adenosine. In addition, tp of intra-RA ATP and intra-AR ATP increased substantially and were similar to tp of adenosine. It was concluded that 1) ATP can stimulate vagal afferent terminals not only in the lungs but also in the heart, 2) the latter constitutes the vagal component of the negative chronotropic action of intra-RA or intra-AR ATP on SN automatically, and 3) the asymmetry in the vagal afferent traffic elicited by ATP in the heart (i.e., right vagal dominance) supersedes the symmetrical vagal afferent traffic triggered by intrapulmonary ATP.
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http://dx.doi.org/10.1152/ajpheart.1996.270.5.H1785 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States.
The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan.
An enzyme with strong single-stranded DNA (ssDNA) ligation activity would be advantageous for many molecular biology applications. However, currently available enzymes exhibit only limited activity. Here, we identified an enzyme with strong ssDNA ligation activity upon searching the databases for proteins homologous to TS2126 RNA ligase, the known enzyme with the highest yet limited ssDNA ligation activity.
View Article and Find Full Text PDFAnal Chem
January 2025
Guangdong Key Laboratory of Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, P. R. China.
Understanding the molecular energy metabolism of single cells in the nucleolus stress response induced by mild-photothermal therapy (mPTT) is of great importance for investigating the photothermal lethal mechanism. Herein, we successfully fabricated a "turn-on"-type fluorescent nanoprobe based on the fluorescently labeled aptamers (FAM-ATP-apt and Cy3-GTP-apt) and TiCT MXene. When the adapters on the nanoprobes bonded to intracellular ATP and GTP, the fluorescence of the nanoprobes was restored.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya, Japan.
The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured ATP release during hypotonic stress using a real-time ATP luminescence imaging system in breast cell lines and in primary cultured mammary cells.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: Damage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to predict the prognosis and immunotherapy responsiveness of PDAC patients using DAMPs-related genes.
Methods: K-means analysis was used to identify the DAMPs-related subtypes of 175 PDAC cases.
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