Low Oxygen Availability Research Articles

Co-feeding strategy alleviates hypoxic stress in large-scale bioreactor for optimal production of secretory recombinant proteins in Pichia pastoris.

The loss of mixing efficiency inherent to bioreactor process operated at large-scale yields to the formation of concentration gradient and thus to heterogeneous culture conditions. For processes operated with methanol feeding, P. pastoris faces oscillatory culture conditions that significantly affect the cell ability to produce secretory recombinant proteins at high yield. Extended cell residence time in microenvironments of high methanol concentration and low oxygen availability that are typically found in the upper part of the bioreactor near the feeding point, triggers the unfolded protein response (UPR) and thus impairs proper protein secretion. Methanol co-feeding with sorbitol was shown herein to reduce the UPR response and to restore productivity of secreted protein.

CopA3 treatment suppressed multidrug resistivity in HCT-116 cell line by p53-induced degradation of hypoxia-inducible factor 1α

The major reason for multidrug resistance is the failure of chemotherapy in many tumors, including colon cancer. Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor that simulates multiple cellular response to hypoxia. HIF-1α has been known to play a vital role towards tumor resistance; however, its mechanism of action is still not fully elucidated. N this study, we found that HIF-1α remarkably modulated drug resistance-associated proteins upon CopA3 peptide treatment against colon cancer cells. Abnormal rates of tumor growth along with high metastatic potential lacks the susceptibility towards cellular signals is a key characteristic in many tumor types. Moreover, in growing tumors, cells are exposed to insufficient nutrient supply and low oxygen availability. These stress force them to switch into adaptable and aggressive phenotypes. Our study investigated the interaction of HIF-1α and MDR gene association upon CopA3 treatment in the tumor microenvironment. We demonstrate that the multidrug resistance gene is associated with tumor resistance to chemotherapeutics, which upon CopA3 treatment promotes p53 activation and proteasomal degradation of HIF-1α, effecting the angiogenesis response to hypoxia. p53 downregulation augments HIF-1-dependent transcriptional activation of VEGF in response to oxygen deprivation.

Effect of Elevated Oxygen Concentration on the Yeast Yarrowia lipolytica for the Production of γ-Decalactones in Solid State Fermentation

To study the effect of elevated oxygen concentrations on β-oxidation for the production of lactones by Yarrowia lipolytica W29 in solid state fermentation (SSF), experiments using oxygen-enriched air, with different initial concentrations of oxygen ratio, were carried out. Growth kinetics using an oxygen ratio of 30% reached the stationary phase earlier than other conditions used. In addition, the production of γ-decalactone and 3-hydroxy-γ-decalactone reached the maximal concentrations of 270 mg L−1 and 1190 mg L−1, respectively. Using higher initial oxygen ratios (40% and 50%), an incomplete growth inhibition occurred and resulted in a higher concentration of yeast at the stationary phase and a slightly higher 3-hydroxy-γ-decalactone accumulation. When oxygen-enriched air (oxygen ratio of 30%) was injected twice (at 0 and 20 h), 3-hydroxy-γ-decalactone reached a higher concentration (1620 mg L−1) and it reached a very high concentration of 4600 mg L−1 in the condition of oxygen-enriched air injected many times (at 0, 20, 35, 48 and 60 h). This study suggested that oxygen is required for the production of 3-hydroxy-γ-decalactone in SSF. Oxygen may be consumed preferentially for long-chain fatty acid oxidations rather than at C10-level. Furthermore, the production of γ-decalactone may be improved by optimizing the growth conditions to reach a very high specific growth rate. A low oxygen availability in the system at the stationary growth phase led to an inhibition of γ-decalactone degradation. From the present work, an alternative system is proposed as a novel model to study the effect of elevated oxygen concentration in SSF.

Living together: The role of Candida albicans in the formation of polymicrobial biofilms in the oral cavity.

The oral cavity of humans is colonized by diversity of microbial community, although dominated by bacteria, it is also constituted by a low number of fungi, often represented by Candida albicans. Although in the vast minority, this usually commensal fungus under certain conditions of the host (e.g., immunosuppression or antibiotic therapy), can transform into an invasive pathogen that adheres to mucous membranes and also to medical or dental devices, causing mucosal infections. This transformation is correlated with changes in cell morphology from yeast-like cells to hyphae and is supported by numerous virulence factors exposed by C. albicans cells at the site of infection, such as multifunctional adhesins, degradative enzymes, or toxin. All of them affect the surrounding host cells or proteins, leading to their destruction. However, at the site of infection, C. albicans can interact with different bacterial species and in its filamentous form may produce biofilms-the elaborated consortia of microorganisms, that present increased ability to host colonization and resistance to antimicrobial agents. In this review, we highlight the modification of the infectious potential of C. albicans in contact with different bacterial species, and also consider the mutual bacterial-fungal relationships, involving cooperation, competition, or antagonism, that lead to an increase in the propagation of oral infection. The mycofilm of C. albicans is an excellent hiding place for bacteria, especially those that prefer low oxygen availability, where microbial cells during mutual co-existence can avoid host recognition or elimination by antimicrobial action. However, these microbial relationships, identified mainly in in vitro studies, are modified depending on the complexity of host conditions and microbial dominance in vivo.

Analysis of Polycyclic Aromatic Hydrocarbon Emissions from a Pilot Scale Silicon Process with Flue Gas Recirculation

Flue gas recirculation (FGR) is a method used in several industries to control emissions and process conditions, such as NOx reduction and temperature levels, and increase the CO2 concentration in the off-gas, to be better suited for methods of carbon capture. In this study, the influence of FGR, varying levels of flue gas flow and oxygen concentration on the emissions of polycyclic aromatic hydrocarbons (PAHs) was investigated during Si alloy production. In addition, computational fluid dynamics (CFD) modeling was performed using OpenFOAM for combustion of C2H2 and H2 with varying O2 levels to simulate FGR and to gain better insight into the impact of furnace operations on the PAH evolution. Experimental results show that increasing FGR (0–82.5%) and decreasing levels of oxygen (20.7–13.3 vol %) increase the PAH-42 concentration from 14.1 to 559.7 μg/Nm3. This is supported by the simulations, where increased formation of all PAHs species was observed at high levels of FGR, especially for the lighter aromatic species (like benzene and naphthalene), due to the lower availability of oxygen and the reduction in temperature. Residence time was identified as another key parameter to promote complete combustion of PAHs. Benzene oxidation can be prevented with temperatures lower than 1000 K and residence times smaller than 1 s, while complete oxidation is found at temperatures of around 1500 K.

Thermal treatment of petroleum-contaminated marine sediment according to oxygen availability and temperature: Product quality as a potential plant-growth medium

The sustainable management of dredged sediment from contaminated sites needs to consider the end-use of the treated sediment. In this regard, modifying conventional sediment treatment techniques to generate a product that is suitable for a range of terrestrial uses is necessary. In the present study, we evaluated the product quality of treated sediment as a potential plant-growth medium following the thermal treatment of marine sediment contaminated by petroleum. The contaminated sediment was subject to thermal treatment at temperatures of 300, 400, or 500 °C, and no, low, or moderate oxygen availability, and the resulting treated sediment was analyzed in terms of its bulk properties, spectroscopic properties, organic contaminants, water-soluble salts and organic matter, and the leachability and extractability of heavy metals. All operational combinations for the treatment process reduced the total petroleum hydrocarbon content of the sediment from 4922 mg kg−1 to lower than 50 mg kg−1. The thermal treatment process stabilized the heavy metals in the sediment, reducing the zinc and copper concentration by up to 58.9% and 89.6%, respectively, in the leachate from the toxicity characteristic leaching procedure. The hydrophilic organic and/or sulfate salt byproducts of the treatment were phytotoxic, but these can easily be removed by washing the sediment with water. By combining the sediment analysis results with experimental data from barley germination and early-growth tests, the end product was found to be of higher quality when higher temperatures and lower oxygen availability were employed in the treatment process. These findings demonstrate that it is possible to retain the natural organic resources of the original sediment by optimizing the thermal treatment, thus ensuring a suitably high product quality for use as a plant-growth medium.

HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases

Angiogenesis is the formation of new blood capillaries taking place from preexisting functional vessels, a process that allows cells to cope with shortage of nutrients and low oxygen availability. Angiogenesis may be activated in several pathological diseases, from tumor growth and metastases formation to ischemic and inflammatory diseases. New insights into the mechanisms that regulate angiogenesis have been discovered in the last years, leading to the discovery of new therapeutic opportunities. However, in the case of cancer, their success may be limited by the occurrence of drug resistance, meaning that the road to optimize such treatments is still long. Homeodomain-interacting protein kinase 2 (HIPK2), a multifaceted protein that regulates different molecular pathways, is involved in the negative regulation of cancer growth, and may be considered a "bona fide" oncosuppressor molecule. In this review, we will discuss the emerging link between HIPK2 and angiogenesis and how the control of angiogenesis by HIPK2 impinges in the pathogenesis of several diseases, including cancer.

The role of cell size in shaping responses to oxygen and temperature in fruit flies

Abstract The body size of an animal is strongly coupled to key ecological traits such as fecundity, mortality and growth. Ectothermic animals mature at smaller body sizes in warmer conditions and under low oxygen availability (hypoxia). Whether these responses result from changes in cell size and cell number (which together determine body size) and how such cellular responses may help ectotherms cope with heat and hypoxia is poorly understood. The theory of optimal cell size postulates that cell size imposes constraints on oxygen delivery: Differences in cell size result in differences in membrane surface‐to‐volume ratio, which impact the capacity of cells to take up oxygen and has consequences for growth rate and hence body size. Here, using inbred lines of fruit flies Drosophila melanogaster, which exhibit differences in cell size, we demonstrate that thermal responses in body size are magnified under hypoxia and in lines of flies that exhibit larger cell size. Furthermore, reductions in body size were partly manifested via reductions in cell size, resulting in a coupling between the body mass and cell size of flies. The coupling between cell size and body size was tighter under conditions where oxygen is expected to become limited, that is, warm or hypoxia, supporting the idea that capacity for oxygen uptake is causally related to organismal growth and the resulting body size. Our data indicate that the benefits of diffusive oxygen uptake due to the higher surface‐to‐volume ratios in smaller cells can help explain the temperature‐size rule in this species. Read the free Plain Language Summary for this article on the Journal blog.

Catalytic Oxidation of n-Decane, n-Hexane, and Propane over Pt/CeO2 Catalysts.

Pt species with different chemical states and structures were supported on CeO2 by solution reduction (Pt/CeO2-SR) and wet impregnation (Pt/CeO2-WI) and investigated in catalytic oxidation of n-decane (C10H22), n-hexane (C6H14), and propane (C3H8). Characterization by X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, H2-temperature programming reduction, and oxygen temperature-programmed desorption showed that Pt0 and Pt2+ existed on Pt nanoparticles of the Pt/CeO2-SR sample, which promoted redox, oxygen adsorption, and activation. On Pt/CeO2-WI, Pt species were highly dispersed on CeO2 as the Pt-O-Ce structure, in which surface oxygen decreased significantly. The Pt/CeO2-SR catalyst presents high activity in oxidation of C10H22 with a rate of 0.164 μmol min-1 m-2 at 150 °C. The rate increased with oxygen concentration. Moreover, Pt/CeO2-SR presents high stability on feed stream containing 1000 ppm C10H22 at gas hour space velocity = 30,000 h-1 as low as 150 °C for 1800 min. The low activity and stability of Pt/CeO2-WI were probably related to its low availability of surface oxygen. In situ Fourier transform infrared results showed that the adsorption of alkane occurred through the interaction with Ce-OH. The adsorption of C6H14 and C3H8 was much weaker than that of C10H22, which resulted in the decrease in activity for C6H14 and C3H8 oxidation of Pt/CeO2 catalysts.

Energy metabolism of juvenile scallops Nodipecten subnodosus under acute increased temperature and low oxygen availability

High temperature increases energy demand in ectotherms, limiting their physiological capability to cope with hypoxic events. The present study aimed to assess the metabolic tolerance of juvenile Nodipecten subnodosus scallops to acute hyperthermia combined with moderate hypoxia. A previous study showed that juveniles exhibited a high upper temperature limit (32 °C), but the responses of juveniles to combined hyperthermia and low dissolved oxygen are unknown. Scallops were exposed to control conditions (treatment C: 22 °C, ∼7.1 mg O2 L−1 or PO2 156.9 mmHg), acute hyperthermia under normoxia (treatment T: 30 °C, ∼6.0 mg O2 L−1 or PO2 150.9 mmHg) or acute hyperthermia plus hypoxia (treatment TH: 30 °C, ∼2.5 mg O2 L−1 or PO2 62.5 mmHg) for 18 h. In T, juveniles exhibited an enhanced oxygen consumption, together with a decrease in adenylate energy charge (AEC) and arginine phosphate (ArgP), and with no changes in metabolic enzyme activity in the muscle. In TH, scallops maintained similar AEC and ArgP levels in muscle as those observed in T treatment. This response occurred along with the accumulation of inosine monophosphate and hypoxanthine. Besides, reduced citrate synthase and pyruvate kinase activities, enhanced hexokinase activity, and a higher octopine dehydrogenase/lactate dehydrogenase ratio in the mantle indicated the onset of anaerobiosis in TH. These responses indicate that juvenile scallops showed tissue-specific compensatory responses regarding their energy balance under moderate hypoxia at high temperatures. Our results give an insight into the tolerance limit of this species to combined hyperthermia and hypoxia in its northern limit of distribution.

Dinitrogen Emissions Dominate Nitrogen Gas Emissions From Soils With Low Oxygen Availability in a Moist Tropical Forest

AbstractLowland tropical forest soils are relatively N rich and are the largest global source of N2O (a powerful greenhouse gas) to the atmosphere. Despite the importance of tropical N cycling, there have been few direct measurements of N2 (an inert gas that can serve as an alternate fate for N2O) in tropical soils, limiting our ability to characterize N budgets, manage soils to reduce N2O production, or predict the future role that N limitation to primary productivity will play in buffering against climate change. We collected soils from across macro‐ and micro‐topographic gradients that have previously been shown to differ in O2 availability and trace gas emissions. We then incubated these soils under oxic and anoxic headspaces to explore the relative effect of soil location versus transient redox conditions. No matter where the soils came from, or what headspace O2 was used in the incubation, N2 emissions dominated the flux of N gas losses. In the macrotopography plots, production of N2 and N2O were higher in low O2 valleys than on more aerated ridges and slopes. In the microtopography plots, N2 emissions from plots with lower mean soil O2 (5%–10%) were greater than in plots with higher mean soil O2 (10%–20%). We estimate an N gas flux of ∼37 kg N/ha/yr from this forest, 99% as N2. These results suggest that N2 fluxes may have been systematically underestimated in these landscapes, and that the measurements we present call for a reevaluation of the N budgets in lowland tropical forest ecosystems.

HIF-1 ACTIVATION AND INFLAMMATORY RESPONSES TO HYPOXIA

Acute hypoxia is a significant physiological danger during high-altitude flying and military aircraft missions. The human brain requires a constant supply of oxygen to function properly, and is susceptible to settings with low availability of air oxygen. Hypoxia can influence inflammatory signalling, and both central and systemic responses can activate HIF pathway genes. HIFs are critical molecules that regulate inflammation andhypoxia, ensuring appropriate cell function and survival. Hypoxia is the condition in which insufficient oxygen reaches the body's tissues. It can be caused by a decrease in partial oxygen pressure (PO2) in the environment, problems with breathing and/or oxygen transport, or the inability of tissues to utilise oxygen. Different organs are hypoxic due to differences in tissue oxygen tensions, which are determined by differences in aerobic metabolism. Extremely hypoxic individuals have the most dramatic systemic and neurological adaptations to persistent hypoxia. In this review, we provide an overview of central and systemic responses to hypoxia and discuss the activation of HIF-1 pathway.

Influence of Different Environments and Temperatures on the Photo-Oxidation Behaviour of the Polypropylene.

The photo-oxidation of polypropylene at two different temperatures and in three different environments-air, distilled water and sea water-has been followed as a function of the irradiation time. The photo-oxidation kinetic is dramatically dependent on the amount of oxygen available for the oxidation reactions and on the temperature. While the photo-oxidation is very fast in air, the degradation is much slower in the two aqueous media. The degradation in sea water is slightly slower than in distilled water. In all cases, the degradation kinetic increases remarkably with the temperature. This behavior has been attributed to the lower oxygen availability for the oxidation reactions of the polymers. The light difference of the degradation kinetic between the two aqueous media depends on the small difference of the oxygen concentration at the test temperatures of 40 and 70 °C. At the latter temperature, the difference between the degradation kinetic in distilled water and sea water is still less important because increasing the temperature decreases the solubility of the oxygen, and it tends to became very similar in both samples of water.

Competition in the deep sea: phylogeny determines destructive impact of wood-boring xylophagaids (Mollusca: Bivalvia)

How biotic interactions contribute to structuring deep-sea communities remains poorly known. An example of exploitation competition, in which over time one species dominates a habitat to preclude its use by competitors, is highlighted here. Sunken wood is the obligate habitat of deep-sea wood borers of the Xylophagaidae Purchon, 1941 which eat wood and, with symbiotic bacteria, digest it. Enigmatically, some wood falls remain robust despite xylophagaid boring. Xylophagaids bore other wood falls so heavily that they crumble after just a few months. We perform a meta-analysis of experimental wood deployments and view the results from a phylogenetic perspective. Of 15 deployments recovered after 5 to 25 months from 200 to 3232 m deep, seven were so heavily bored to be crushable by hand. Eight were bored but remained robust. The groups did not significantly differ in wood size, type, temperature, depth, or duration. Members of the Xylophaga dorsalis (Turton, 1819) clade, reported in two studies to recruit and bore faster than confamilials, bored all seven crushable deployments; seven of the eight intact deployments were bored by other xylophagaids. Fecal chimneys line and thus narrow the boreholes of this clade; fluid flow is impeded, a clear liability. The lignin-rich fecal chimneys may, however, cue larval settlement and at resultant high population densities, lower oxygen availability. Members of the X. dorsalis clade, being hypoxia-tolerant, thrive but other xylophagaids appear to suffer, perhaps due to interference competition. The shared derived characters that unite this clade allow them to exploit low-oxygen wood that is intolerable for competitors.

Atomic oxygen assisted CO2 conversion: A theoretical analysis

With climate change still a pressing issue, there is a great need for carbon capture, utilisation and storage (CCUS) methods. We propose a novel concept where CO2 conversion is accomplished by O2 splitting followed by the addition of O atoms to CO2. The latter is studied here by means of kinetic modelling. In the first instance, we study various CO2/O ratios, and we observe an optimal CO2 conversion of around 30–40% for 50% O addition. Gas temperature also has a large influence, with a minimum temperature of around 1000 K to a maximum of 2000 K for optimal conversion. In the second instance, we study various CO2/O/O2 ratios, due to O2 being a starting gas. Also here we define optimal regions for CO2 conversion, which reach maximum conversion for a CO2 fraction of 50% and an O/O2 ratio bigger than 1. Those can be expanded by heating on one hand, for low atomic oxygen availability, and by quenching after reaction on the other hand, for cases where the temperatures are too high. Our model predictions can serve as a guideline for experimental research in this domain.

Comparative genomic analysis of the aldehyde dehydrogenase gene superfamily in Arabidopsis thaliana - searching for the functional key to hypoxia tolerance.

Flooding entails different stressful conditions leading to low oxygen availability for respiration and as a result plants experience hypoxia. Stress imposed by hypoxia affects cellular metabolism, including the formation of toxic metabolites that dramatically reduce crop productivity. Aldehyde dehydrogenases (ALDHs) are a group of enzymes participating in various aspects of plant growth, development and stress responses. Although we have knowledge concerning the multiple functionalities of ALDHs in tolerance to various stresses, the engagement of ALDH in plant metabolism adjustment to hypoxia is poorly recognized. Therefore, we explored the ALDH gene superfamily in the model plant Arabidopsis thaliana. Genome-wide analyses revealed that 16 AtALDH genes are organized into ten families and distributed irregularly across Arabidopsis 5 chromosomes. According to evolutionary relationship studies from different plant species, the ALDH gene superfamily is highly conserved. AtALDH2 and ALDH3 are the most numerous families in plants, while ALDH18 was found to be the most distantly related. The analysis of cis-acting elements in promoters of AtALDHs indicated that AtALDHs participate in responses to light, phytohormones and abiotic stresses. Expression profile analysis derived from qRT-PCR showed the AtALDH2B7, AtALDH3H1 and AtALDH5F1 genes as the most responsive to hypoxia stress. In addition, the expression of AtALDH18B1, AtALDH18B2, AtALDH2B4, and AtALDH10A8 was highly altered during the post-hypoxia-reoxygenation phase. Taken together, we provide comprehensive functional information on the ALDH gene superfamily in Arabidopsis during hypoxia stress and highlight ALDHs as a functional element of hypoxic systemic responses. These findings might help develop a framework for application in the genetic improvement of crop plants.

Modulation of oxidative neurometabolism in ischemia/reperfusion by nitrite.

Nitrite has been viewed essentially as an inert metabolic endpoint of nitric oxide (•NO). However, under certain conditions, nitrite can be a source of •NO. In the brain, this alternative source of •NO production independent of nitric oxide synthase activity may be particularly relevant in ischemia/reperfusion (I/R), where low oxygen availability limits enzymatic production of •NO. Notably, in vivo concentration of nitrite can be easily increased with diet, through the ingestion of nitrate-rich foods, opening the window for a therapeutic intervention based on diet. Considering the modulation of mitochondrial respiration by •NO, we have hypothesized that the protective action of nitrite in I/R may also result from modulation of mitochondrial function. We used high-resolution respirometry to evaluate the effects of nitrite in two in vitro models of I/R. In both cases, an increase in oxygen flux was observed following reoxygenation, a phenomenon that has been coined "oxidative burst". The amplitude of this "oxidative burst" was decreased by nitrite in a concentration-dependent manner. Additionally, a pilot in vivo study in which animals received a nitrate-rich diet as a strategy to increase circulating and tissue levels of nitrite also revealed that the "oxidative burst" was decreased in the nitrate-treated animals. These results may provide mechanistic support to the observation of a protective effect of nitrite in situations of brain ischemia.

Crosstalk between NADPH oxidases and the Hippo pathway coactivator Yes-Associated Protein promotes the cardiac response to hypoxia

Abstract Background The Hippo pathway is an evolutionarily conserved regulator of organ size and tumorigenesis. YAP is the main effector downstream of the Hippo pathway. Hippo activation induces an inhibitory YAP serine phosphorylation and nuclear exit/ proteolytic degradation, thereby negatively regulating YAP activity. YAP activates TEAD transcription factors, thereby controlling growth and death in many cell types. In the adult heart, YAP has been shown to contribute to the regenerative response in conditions characterized by hypoxia and increased load of reactive oxygen species (ROS). While the multicomponent family of NADPH oxidases with its essential subunit p22phox contributes to ROS generation in the compromised heart, it is not known whether there is a link between YAP and NADPH oxidases. Aim We investigated whether YAP is sensitive to hypoxia and interferes with NADPH oxidases in vitro in cardiomyoblasts and in vivo in murine hearts. Methods H9C2 cardiomyoblasts or isolated adult murine cardiomyocytes (CMCs) were exposed to 0.1% O2 for different time points. H9C2 cells were transduced with constitutively active YAP or transfected with siRNAs against Yap and p22phox. For in vivo experiments, mice deficient in p22phox and wildtype mice were exposed to 10% O2. ROS levels were measured by DHE fluorescence or electron paramagnetic resonance. Cell cycle analysis and cell counting were performed by FACS. Localization and activation status of YAP were assessed by immunofluorescence, western blot and nuclear fractionation. DNA binding was analyzed by electro mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Results Hypoxia increased YAP protein levels, nuclear translocation and activity while Yap phosphorylation was decreased in H9C2 cells and in CMCs. Treatment with antioxidants or depletion of p22phox prevented these responses. In line, hypoxic exposure for only one day was already sufficient to increase YAP expression in hearts from wildtype mice but not in hearts from p22phox-deficient mice. Furthermore, depletion of p22phox and of YAP reduced number, cell cycle progression and hypertrophy of H9C2 cells under hypoxia. Similarly, H9C2 cells stably expressing constitutively active YAP showed increased cell numbers, cell cycle progression and cell hypertrophy dependent on p22phox and ROS. Interestingly, YAP overexpressing H9C2 cells showed increased ROS generation, concomitant with elevated expression of p22phox. In line, p22phox and YAP levels were enhanced in mice lacking the YAP upstream kinase Mst1. Reporter gene assays, EMSA and ChIP analyses showed that TEAD and YAP bind to the p22phox promoter in H9C2 cells. Conclusion These findings show that hypoxia increases YAP expression and activity dependent on ROS derived from its target p22phox in the heart. This feed forward loop between YAP and NADPH oxidases might promote pulmonary hypertension and other cardiovascular diseases associated with low oxygen availability. Funding Acknowledgement Type of funding sources: None.

Abstract IA017: Impact of oxygen and nutrient availability on sarcoma tumor neighborhood

Abstract Molecular oxygen (O2) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP- consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best- studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine- tuning the responses to hypoxic stress. Citation Format: M. Celeste Simon. Impact of oxygen and nutrient availability on sarcoma tumor neighborhood [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA017.

Ruthenium(II) Polypyridyl Complexes for Antimicrobial Photodynamic Therapy: Prospects for Application in Cystic Fibrosis Lung Airways.

Antimicrobial photodynamic therapy (aPDT) depends on a variety of parameters notably related to the photosensitizers used, the pathogens to target and the environment to operate. In a previous study using a series of Ruthenium(II) polypyridyl ([Ru(II)]) complexes, we reported the importance of the chemical structure on both their photo-physical/physico-chemical properties and their efficacy for aPDT. By employing standard in vitro conditions, effective [Ru(II)]-mediated aPDT was demonstrated against planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus strains notably isolated from the airways of Cystic Fibrosis (CF) patients. CF lung disease is characterized with many pathophysiological disorders that can compromise the effectiveness of antimicrobials. Taking this into account, the present study is an extension of our previous work, with the aim of further investigating [Ru(II)]-mediated aPDT under in vitro experimental settings approaching the conditions of infected airways in CF patients. Thus, we herein studied the isolated influence of a series of parameters (including increased osmotic strength, acidic pH, lower oxygen availability, artificial sputum medium and biofilm formation) on the properties of two selected [Ru(II)] complexes. Furthermore, these compounds were used to evaluate the possibility to photoinactivate P. aeruginosa while preserving an underlying epithelium of human bronchial epithelial cells. Altogether, our results provide substantial evidence for the relevance of [Ru(II)]-based aPDT in CF lung airways. Besides optimized nano-complexes, this study also highlights the various needs for translating such a challenging perspective into clinical practice.