There are abundant animal data attempting to identify the neural circuitry involved in cardiovascular control. Translating this research into humans has been made possible using functional neurosurgery during which deep brain stimulating electrodes are implanted into various brain nuclei for the treatment of chronic pain and movement disorders. This not only allows stimulation of the human brain, but also presents the opportunity to record neural activity from various brain regions. This symposium review highlights key experiments from the past decade that have endeavoured to identify the neurocircuitry responsible for integrating the cardiovascular response to exercise in humans. Two areas of particular interest are highlighted: the periaqueductal grey and the subthalamic nucleus. Our studies have shown that the periaqueductal grey (particularly the dorsal column) is a key part of the neurocircuitry involved in mediating autonomic changes adapted to ongoing behaviours. Emerging evidence also suggests that the subthalamic nucleus is not only involved in the control of movement, but also in the mediation of cardiovascular responses. Although these sites are unlikely to be the 'command' areas themselves, we have demonstrated that the two nuclei have the properties of being key integrating sites between the feedback signals from exercising muscle and the feedforward signals from higher cortical centres.
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http://dx.doi.org/10.1113/expphysiol.2011.060848 | DOI Listing |
J Leukoc Biol
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA.
Regulated sequential exocytosis of neutrophil granules is essential in orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several pre-clinical models of inflammatory disease.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Republic of Korea.
The design of organic-peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca-binding organic-peptide hybrid. The designed molecule, designated Ca-binding switch (CaBS), combines an EF-hand motif from classical Ca-binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light.
View Article and Find Full Text PDFInt J Biometeorol
January 2025
Southeast Regional Climate Center, Department of Geography and Environment, University of North Carolina, Chapel Hill, NC, 27514, USA.
The relationship between diurnal temperature range (DTR) and daily mortality from 2005 to 2020 is examined for seven large metropolitan areas in Virginia using distributed lag non-linear models that control for temperature and humidity. The relative risk of mortality increases for very high DTR, and there is a short lag effect of several days. High risk DTR days are rare, typically occurring less than 1% of the time at most locations.
View Article and Find Full Text PDFJ Am Heart Assoc
January 2025
Division of Epidemiology and Community Health, School of Public Health University of Minnesota Minneapolis MN USA.
Background: The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.
Methods And Results: We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987-1989).
J Exp Biol
January 2025
Laboratory of Physiology, Atmosphere and Ocean Research Institute, University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba, 277-8564, Japan.
In general, ghrelin is known as one of the orexigenic hormones in mammals. On the other hand, it has been shown that ghrelin inhibits water intake, which appear to be inconsistent with its role in the feeding response. In this study, the effect of ghrelin on water intake was comprehensively addressed using conscious seawater-acclimated eels known as an experimental model for water drinking behaviour.
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