Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors

The current restrictive criteria for gasotransmitters exclude oxygen(O_(2))as a gasotransmitter in vertebrates.In this manuscript,I propose a revision of gasotransmitter criteria to include O_(2) per se as a signaling molecule and'essential gasotransmitter'for vertebrates.This revision would enable us to search for protein-based O_(2)-binding sensors(gasoreceptors)in all cells in the brain or other tissues rather than specialized tissues such as the carotid body or gills.If microorganisms have protein-based O_(2)-binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains,then eukaryotic cells must also have O_(2)-binding sensors or gasoreceptors.Just as there are proteinbased receptor(s)for nitric oxide(GUCY1A,GUCY1B,CLOCK,NR1D2)in cells of diverse tissues,it is reasonable to consider that there are protein-based receptors for O_(2) in cells of diverse tissues as well.In mammals,O_(2) must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O_(2).Accepting O_(2) as an essential gasotransmitter will enable us to search for gasoreceptors not only for O_(2) but also for other nonessential gasotransmitters such as hydrogen sulfide,ammonia,methane,and ethylene.It will also allow us to investigate the role of environment-derived metal ions in acute gas(or solute)sensing within and between organisms.Finally,accepting O_(2) per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.