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Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5-10 cmH2O) imposed 4.9 ± 2.0% strain and resulted in 11.6 ± 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5-30 cmH2O) achieved 62.9 ± 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm = 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.
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http://dx.doi.org/10.1152/japplphysiol.00009.2013 | DOI Listing |
bioRxiv
June 2025
Department of Entomology and Nematology, University of California, Davis, CA 95616, USA.
The liver circadian clock and hepatic transcriptome are highly responsive to metabolic signals generated from feeding-fasting rhythm. Previous studies have identified a number of nutrient-sensitive signaling pathways that could interpret metabolic input to regulate rhythmic hepatic biology. Here, we investigated the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) in mediating metabolic regulation of rhythmic biology in the liver.
View Article and Find Full Text PDFJ Appl Physiol (1985)
November 2024
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
Proteins
July 2024
Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, USA.
Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the formation of extracellular amyloid-β (Aβ) plaques. The underlying cause of AD is unknown, however, post-translational modifications (PTMs) of Aβ have been found in AD patients and are thought to play a role in protein aggregation. One such PTM is pyroglutamylation, which can occur at two sites in Aβ, Glu3 and Glu11.
View Article and Find Full Text PDFNanomaterials (Basel)
November 2022
Department of Electrical and Electronics Engineering, Konkuk University, Seoul 05029, Republic of Korea.
In this work, a hybrid-phase transition field-effects-transistor (hyper-FET) integrated with phase-transition materials (PTM) and a multi-nanosheet FET (mNS-FET) at the 3 nm technology node were analyzed at the device and circuit level. Through this, a benchmark was performed for presenting device design guidelines and for using ultra-low-power applications. We present an optimization flow considering hyper-FET characteristics at the device and circuit level, and analyze hyper-FET performance according to the phase transition time (TT) and baseline-FET off-leakage current (I) variations of the PTM.
View Article and Find Full Text PDFFront Mol Biosci
June 2022
School of Biosciences and Bioengineering (BSBE), Indian Institute of Technology (IIT)- Mandi, Mandi, India.
Cardiac fibrosis-mediated heart failure (HF) is one of the major forms of end-stage cardiovascular diseases (CVDs). Cardiac fibrosis is an adaptive response of the myocardium upon any insult/injury. Excessive deposition of collagen molecules in the extracellular matrix (ECM) is the hallmark of fibrosis.
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