Inspired oxygen: present, past, and future

As earthlings, we take the oxygen in the air that we breathe for granted. Few people realize that this easy access to oxygen makes us unique in the whole universe. Nowhere else in our planetary system or in distant stars has stable oxygen ever been detected. However, the present plentiful supply of oxygen in our atmosphere was not always there. Long after the earth was formed some 4.5 billion years ago, the PO2 in the atmosphere was near zero, and it remained so for millions of years. But about 2 billion years ago, the PO2 dramatically increased to as high as 200 mmHg during the Great Oxygen Event, due to the activity of microorganisms, the cyanobacteria. Subsequently the oxygen level fell to the intermediate values that we have today. Here we also look to the future, for example, the next 50 years. This period will be special because it will include the beginnings of human space exploration, initially to the Moon and Mars. Neither of these has atmospheric oxygen. Nevertheless, plans to visit and live on both of these are developing rapidly. We consider the fascinating problems of how to how to ensure that sufficient oxygen will be available for groups of people . While it is interesting to discuss these issues now, we can expect that major advances will be made in the next few years.

Conditional Mutation of Hand1 in the Mouse Placenta Disrupts Placental Vascular Development Resulting in Fetal Loss in Both Early and Late Pregnancy

Congenital heart defects (CHD) affect approximately 1% of all live births, and often require complex surgeries at birth. We have previously demonstrated abnormal placental vascularization in human placentas from fetuses diagnosed with CHD. Hand1 has roles in both heart and placental development and is implicated in CHD development. We utilized two conditionally activated Hand1A126fs/+ murine mutant models to investigate the importance of cell-specific Hand1 on placental development in early (Nkx2-5Cre) and late (Cdh5Cre) pregnancy. Embryonic lethality occurred in Nkx2-5Cre/Hand1A126fs/+ embryos with marked fetal demise occurring after E10.5 due to a failure in placental labyrinth formation and therefore the inability to switch to hemotrophic nutrition or maintain sufficient oxygen transfer to the fetus. Labyrinthine vessels failed to develop appropriately and vessel density was significantly lower by day E12.5. In late pregnancy, the occurrence of Cdh5Cre+;Hand1A126fs/+ fetuses was reduced from 29% at E12.5 to 20% at E18.5 and remaining fetuses exhibited reduced fetal and placental weights, labyrinth vessel density and placenta angiogenic factor mRNA expression. Our results demonstrate for the first time the necessity of Hand1 in both establishment and remodeling of the exchange area beyond early pregnancy and in patterning vascularization of the placental labyrinth crucial for maintaining pregnancy and successful fetal growth.

Multi-Omic Meta-Analysis of Transcriptomes and the Bibliome Uncovers Novel Hypoxia-Inducible Genes

Hypoxia is a condition in which cells, tissues, or organisms are deprived of sufficient oxygen supply. Aerobic organisms have a hypoxic response system, represented by hypoxia-inducible factor 1-α (HIF1A), to adapt to this condition. Due to publication bias, there has been little focus on genes other than well-known signature hypoxia-inducible genes. Therefore, in this study, we performed a meta-analysis to identify novel hypoxia-inducible genes. We searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and manually curated it. We selected the genes that are differentially expressed by hypoxic stimulation, and evaluated their relevance in hypoxia by performing enrichment analyses. Next, we performed a bibliometric analysis using gene2pubmed data to examine genes that have not been well studied in relation to hypoxia. Gene2pubmed data provides information about the relationship between genes and publications. We calculated and evaluated the number of reports and similarity coefficients of each gene to HIF1A, which is a representative gene in hypoxia studies. In this data-driven study, we report that several genes that were not known to be associated with hypoxia, including the G protein-coupled receptor 146 gene, are upregulated by hypoxic stimulation.

Effects of Methanolic Extract of Ginkgo biloba Leaf against Hypoxia-Induced Lethality in Mice

Introduction: Hypoxia defines as a condition in which body tissues do not take sufficient oxygen supply. Chronic hypoxia has various medical consequences. Recently, the role of hypoxia in the progression of COVID-19 disease has been proven. Ginkgo biloba is a valuable plant from more than 2000 years ago. Ginkgo has antioxidant activity and exhibits good scavenging activity on the free radicals therefore, it is considered helpful in treating diseases associated with the generation of free radicals, including chronic inflammation, cerebral infarction, ischemic heart disease, and aging.Material and Methods: In this study, anti-hypoxic activities of G. biloba methanolic leaf extract have been determined against hypoxia-induced lethality in mice to understand its usefulness in treating ischemia.Results: The extract showed weak activity in asphyctic model. At 125 mg/kg, it significantly delayed the time of death compared to the control group (p<0.05) but did not show any activities in haemic or circulatory hypoxia tests even at a higher tested dose, 250 mg/kg. Although, at this dose, extract prolonged the survival time more than 1 minute in circulatory model, but this increase was not statistically significant.Conclusion: In conclusion, results from this study showed that extract has weak anti-hypoxic effects in the treatment of hypoxia.

A dialysis doctor’s memories with COVID-19 disease

This is the testimony of a nephrologist who was infected at the very beginning of the pandemic, in France, while treating his patients. On April 8, 2020, as he was finishing visiting his patients, he experienced myalgia, dyspnea, chills and fever. After two days of trying to stay at home, it became necessary to admit him to the intensive care unit to ensure proper treatment and sufficient oxygen therapy. In this testimony, he describes his own experience as a sick doctor, the effectiveness of the treatments he received, the empathy of his colleagues and the caregivers who took care of him, in a diary kept from day to day. This was followed by a long period of rehabilitation during which he wrote a plea to promote home dialysis methods in order to limit the contamination of end-stage kidney disease patients on dialysis. The editorial staff has deemed it useful to publish this medical testimony full of humanity, written with modesty and the will to bring support and hope to those brutally victimized by the COVID-19 disease.

Flow increases tolerance of heat and hypoxia of an aquatic insect

Recent experiments support the idea that upper thermal limits of aquatic insects arise, at least in part, from a lack of sufficient oxygen: rising temperatures typically stimulate metabolic demand for oxygen more than they increase rates of oxygen supply from the environment. Consequently, factors influencing oxygen supply, like water flow, should also affect thermal and hypoxia tolerance. We tested this hypothesis by measuring the effects of experimentally manipulated flows on the heat and hypoxia tolerance of aquatic nymphs of the giant salmonfly (Plecoptera: Pteronarcys californica ), a common stonefly in western North America. As predicted, stoneflies in flowing water (10 cm s −1 ) tolerated water that was approximately 4°C warmer and that contained approximately 15% less oxygen than did those in standing water. Our results imply that the impacts of climate change on streamflow, such as changes in patterns of precipitation and decreased snowpack, will magnify the threats to aquatic insects from warmer water temperatures and lower oxygen levels.

Photosynthetically stimulated bioerosion in symbiotic sponges: the role of glycerol and oxygen

On coral reefs, some of the most aggressive calcium carbonate eroders are dinoflagellate-hosting sponges of the genus Cliona. Like in other marine taxa, the influence of these symbiotic microorganisms on the metabolism of the host sponge, and thereby on erosion of the surrounding ecosystem, is increasingly acknowledged. Despite elevating pH (and hence carbonate saturation state), dinoflagellate photosynthesis promotes bioerosion by their hosts. This paradox might be solved by a spatial isolation of photosynthesis from carbonate dissolution, but it remains unknown which mechanism connects the dinoflagellates’ photosynthesis with the sponge’s bioerosion. Here, we simulate the outcomes of photosynthesis in two separate ways, namely as production of carbon-rich compounds (in this case glycerol) and as an increase in oxygen content. This allows testing their potential to enhance bioerosion rates of sponge holobionts that were preconditioned under variable photosynthetic regimes. We find that glycerol, a commonly shared photosynthate in marine symbioses, stimulates chemical bioerosion rates in the dark of photosynthetically impaired sponges. Chemical bioerosion was all the more limited by availability of sufficient oxygen, while the combination of added glycerol and oxygen boosted chemical bioerosion rates. We argue that under normal physiological conditions, bioerosion is promoted by both organic carbon and oxygen production, and we provide evidence for the storage of photosynthates for night-time use. We further discuss our findings in the context of the current knowledge of the bioerosion mechanism, which we expand by integrating the effects of carbon-rich compounds and oxygen as drivers for bioerosion by Cliona.

Multi-omic meta-analysis of transcriptomes and the bibliome uncovers GPR146 as the novel hypoxia-inducible gene

Hypoxia is a condition in which cells, tissues, or organisms are deprived of sufficient oxygen supply. Aerobic organisms have the hypoxic response system, represented by hypoxia-inducible factor 1-α (HIF1A), to avoid this condition. Because of publication bias, the genes other than well-known signature hypoxia-stimulating genes may not be focused. Therefore, in this study, we performed meta-analysis to identify novel hypoxia-responsive genes. We searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and manually curated it. We selected the genes that are differentially expressed by hypoxic stimulation, and evaluated their relevance in hypoxia by performing enrichment analyses. We then calculated the number of reports and similarity coefficient of each gene for HIF1A (surrogate for hypoxia) using gene2pubmed that provides information about the relationship between gene and publication. Enrichment analysis confirmed that the selected genes were related to hypoxic stimulation, as expected. We then performed gene2pubmed analysis to investigate the genes that had not been fully studied under hypoxia. In this data-driven study, we report that the G protein-coupled receptor 146 gene is upregulated by hypoxic stimulation.