Limited Oxygen Availability Research Articles

Analysis of cell lysis for improved understanding between the shake tube and stirred tank reactor perfusion CHO cell cultures.

Shake tubes (ST) are widely employed to assist the development of the stirred tank reactor (STR) perfusion cell culture. However, cell lysis may be frequently underrestimated and lead to culture performance discrepency between these systems, rendering the ST model ineffective in designing the STR perfusion cultures. In this study, perfusion culture performance bewteen the STR and ST was investigated under various conditions with the analysis of cell lysis. Comparable performance was observed bewteen the two systems at low perfusion rates ( ≤1.0 VVD), except that the specific productivity ( ) of the STR was decreased at =0.5 VVD, which was related to product degradation by cell lysis. In contrast, significant differences in cell maintenance, metabolism, and were found at =2.0 VVD. By the analysis of the authentic cell growth and death kinetics, it was found that cell growth arrest, potentially due to the limited availability of oxygen, led to the stable cell maintenance at VCD≈90 × 106 cells/ml and altered cellular metabolism for the ST, while the continuous decline of VCD and in the STR were related to excessive cell death, subsequently ascribed to the harmful hydrodynamic stress conditions. We further demonstrated that cell lysis accounted for 57.62-76.29% of the total generated biomass in both the reactors and significantly impacted the estimation of process descriptors crucial for understanding the true cellular states. With cell lysis in sight, cell performance can therefore be accurately described and this knowledge can be further leveraged to expedite process development for the perfusion cell culture processes.

Comparative genomic analyses of aerobic planctomycetes isolated from the deep sea and the ocean surface

On the deep and dark seafloor, a cryptic and yet untapped microbial diversity flourishes around hydrothermal vent systems. This remote environment of difficult accessibility exhibits extreme conditions, including high pressure, steep temperature- and redox gradients, limited availability of oxygen and complete darkness. In this study, we analysed the genomes of three aerobic strains belonging to the phylum Planctomycetota that were isolated from two deep-sea iron- rich hydroxide deposits with low temperature diffusive vents. The vents are located in the Arctic and Pacific Ocean at a depth of 600 and 1,734 m below sea level, respectively. The isolated strains Pr1dT, K2D and TBK1r were analyzed with a focus on genome-encoded features that allow phenotypical adaptations to the low temperature iron-rich deep-sea environment. The comparison with genomes of closely related surface-inhabiting counterparts indicates that the deep-sea isolates do not differ significantly from members of the phylum Planctomycetota inhabiting other habitats, such as macroalgae biofilms and the ocean surface waters. Despite inhabiting extreme environments, our “deep and dark”-strains revealed a mostly non-extreme genome biology.

Accelerating healing at high altitudes: Oxygen and bFGF delivery through nanoparticle-loaded gel dressings

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

Microorganisms in beet sugar production – perspective on technological opportunities and risks

The sugar industry has long faced challenges from microorganisms during production. Preventing sugar losses and microbial-related issues such as the formation of organic acids, gases like CO2 or H2, or slimy substances continues to be key concerns. Fortunately, process parameters such as high temperatures, low pH values and limited oxygen availability create unfriendly conditions for microorganisms, and antimicrobial agents have been developed to control microbial growth. However, a proactive approach would utilize the advantageous properties of microorganisms to break down undesirable substances and promote desirable ones. For example, acidic by-products from bacterial metabolism lower the pH and thus stabilize sugar beet cossettes during pressing. Additionally, beneficial metabolic processes have been recognized, such as preferentially utilizing monosaccharides instead of sucrose or selectively degrading undesired substances (e.g., converting nitrite into elemental nitrogen). Modern sequencing techniques continue to identify unknown bacteria with the potential to improve the process. Exploring these bacteria could offer valuable insights for a better microorganism management in beet sugar production. This perspective article discusses the microbial diversity in beet sugar factories and strategies for better utilization of microbial benefits, aiming for sustainable improvements in sucrose extraction. However, extensive research is necessary to identify and characterize suitable bacterial species and how best to exploit them.

Unlocking the efficacy of cement-shell encapsulation for microbial self-healing process of concrete cracks

Oxygen supply and bacterial viability are crucial for efficient calcium carbonate precipitation in concrete crack healing processes. However, the open deliverance of oxygen-releasing compounds (ORCs) and bacterial spores during concrete mixing and casting poses a threat to spore viability and limits oxygen availability. To address these challenges, we developed an innovative approach integrating an oxygen self-supply strategy with bacterial strain B6. As such, B6 spores, along with Ca(OH)2 and CaO2 as oxygen sources and essential nutrients, were embedded within cement-shell microcapsules to build a microbial self-healing system. The result shows that in the presence of oxygen source and nutrients, B6 group (BPN) exhibits successful crack repair, achieving a repair ratio of approximately 100% after 30 days, while other control groups show less effective repair rates (20–60%). Moreover, water permeability significantly improves in the BPN specimens after crack repair, reaching 0 ml/cm−2·min, highlighting the efficacy of the developed self-healing system. Encapsulating the healing agent within cement shell effectively mitigates the reactivity between ORCs (CaO2) and water, thereby facilitating stable oxygen supply and safe delivery of microbial agents during crack healing. Furthermore, in-situ micromorphology and composition identification of crack repair materials affirm the presence of calcium carbonate precipitation to seal the concrete cracks. The encapsulation of healing material within cement shell stands out as an innovative approach, demonstrating an efficient self-healing process of concrete cracks. These findings might unveil new possibilities for bio-concrete to be used in sustainable and resilient construction practices, particularly in environments prone to cracking and water ingress.

Stable-isotope probing combined with amplicon sequencing and metagenomics identifies key bacterial benzene degraders under microaerobic conditions

The primary aim of the present study was to reveal the major differences between benzene-degrading bacterial communities evolve under aerobic versus microaerobic conditions and to reveal the diversity of those bacteria, which can relatively quickly degrade benzene even under microaerobic conditions. For this, parallel aerobic and microaerobic microcosms were set up by using groundwater sediment of a BTEX-contaminated site and 13C labelled benzene. The evolved total bacterial communities were first investigated by 16S rRNA gene Illumina amplicon sequencing, followed by a density gradient fractionation of DNA and a separate investigation of “heavy” and “light” DNA fractions. Results shed light on the fact that the availability of oxygen strongly determined the structure of the degrading bacterial communities. While members of the genus Pseudomonas were overwhelmingly dominant under clear aerobic conditions, they were almost completely replaced by members of genera Malikia and Azovibrio in the microaerobic microcosms. Investigation of the density resolved DNA fractions further confirmed the key role of these two latter genera in the microaerobic degradation of benzene. Moreover, analysis of a previously acquired metagenome-assembled Azovibrio genome suggested that benzene was degraded through the meta-cleavage pathway by this bacterium, with the help of a subfamily I.2.I-type catechol 2,3-dioxygenase. Overall, results of the present study implicate that under limited oxygen availability, some potentially microaerophilic bacteria play crucial role in the aerobic degradation of aromatic hydrocarbons.

Climate change and human impacts on aquatic communities at Etoliko Lagoon in western Greece

The Etoliko Lagoon in western Greece has experienced extensive human modification since the 20th century, both on the surrounding land and in the aquatic environment. To examine human impacts and disentangle climatic from anthropogenic changes, we present a suite of biomarker records that span the past two centuries (∼1790–2011). Specifically, we use terrigenous (n-alkanes, polycyclic aromatic hydrocarbons (PAHs), and phytosterols) and aquatic (dinosterol, brassicasterol, cholesterol, and stigmasterol) biomarkers to document changes in nutrient inputs, combustion, and algal productivity. During most of the 19th and 20th centuries, aquatic communities respond to temperature, forced mainly by solar irradiance and volcanic activity, and precipitation, controlled largely by summer and winter North Atlantic Oscillation (NAO) patterns that determine freshwater runoff. PAHs illustrate the acceleration of coal combustion during the 1800s, and declining concentrations since the 1950s correspond to the implementation of emission controls and reductions in rainfall that likely inhibited PAH transport. As human pressures increased in the late 1900s and water column anoxia grew, the absence of a clear human waste and eutrophication signal suggests that other factors also contributed to limited oxygen availability. Overall, environmental degradation of the late 20th and early 21st centuries is clear and can be attributed to a combination of especially arid conditions and human interferences that altered lagoon hydrography, trophic state, and aquatic community composition.

Geochemistry of BIF in the Quadrilátero ferrífero, Brazil, as a proxy to neoarchean paleoenvironmental and depositional conditions

Precambrian Algoma-type banded iron formations (BIFs) are biochemical metasedimentary rocks formed in the deep water environment relatively close to centers of volcanic expansion and can be characterized on the basis of their paleodepositional environment and the associated rock types. These rocks may contain geochemical signatures indicative of changes in the redox conditions of the Archean ocean. Such variations in the Meso- and Neoarchean are crucial in understanding the processes that led to the gradual increase of oxygen in the early atmosphere, culminating in the Great Oxidation Event (2.4–2.3 Ga). Oxide- and carbonate-facies BIFs were intercepted by drill cores in the Pilar gold deposit in the NE sector of the Quadrilátero Ferrífero (QF), Brazil, located in the Neoarchean Rio das Velhas greenstone belt. These rocks are interbedded with mafic and ultramafic metavolcanic rocks and carbonaceous phyllites. In light of the potential to reconstruct paleodepositional evidence indicative of the Earth's atmospheric redox history based on this stratigraphy, we have considered specific proxies from geological and geochemical observations. Pilar BIFs geochemistry exhibits positive anomalies of La, Eu, and Y, indicating characteristics inherited from seawater and high-temperature hydrothermal fluids. In addition, a superchondritic Y/Ho ratio further supports the influence of seawater. The signatures of the major elements Al2O3 and other immobile elements typical of detrital sediments corroborate the interpretation that these rocks were deposited in a deep marine environment with low clastic influence. Furthermore, negative Ce/Ce*SN anomalies in some sections of the Pilar BIF indicate limited oxygen availability which, together with Mo, U, V, and Zn trace-element enrichment factors, indicate deposition under suboxic/euxinic conditions. This research, together with other similar BIF data from the NW QF provide new insights into the paleoenvironmental conditions prevailing during the formation of the Archean volcano sedimentary basins that compose the southern São Francisco craton (SFC).

Epithelial hypoxia maintains colonization resistance against Candida albicans

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C.albicans expansion. C.albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources invitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C.albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C.albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C.albicans.

A hybrid TIM complex mediates protein import into hydrogenosomes of Trichomonas vaginalis

BackgroundHydrogenosomes are a specific type of mitochondria that have adapted for life under anaerobiosis. Limited availability of oxygen has resulted in the loss of the membrane-associated respiratory chain, and consequently in the generation of minimal inner membrane potential (Δψ), and inefficient ATP synthesis via substrate-level phosphorylation. The changes in energy metabolism are directly linked with the organelle biogenesis. In mitochondria, proteins are imported across the outer membrane via the Translocase of the Outer Membrane (TOM complex), while two Translocases of the Inner Membrane, TIM22, and TIM23, facilitate import to the inner membrane and matrix. TIM23-mediated steps are entirely dependent on Δψ and ATP hydrolysis, while TIM22 requires only Δψ. The character of the hydrogenosomal inner membrane translocase and the mechanism of translocation is currently unknown.ResultsWe report unprecedented modification of TIM in hydrogenosomes of the human parasite Trichomonas vaginalis (TvTIM). We show that the import of the presequence-containing protein into the hydrogenosomal matrix is mediated by the hybrid TIM22-TIM23 complex that includes three highly divergent core components, TvTim22, TvTim23, and TvTim17-like proteins. The hybrid character of the TvTIM is underlined by the presence of both TvTim22 and TvTim17/23, association with small Tim chaperones (Tim9-10), which in mitochondria are known to facilitate the transfer of substrates to the TIM22 complex, and the coupling with TIM23-specific ATP-dependent presequence translocase-associated motor (PAM). Interactome reconstruction based on co-immunoprecipitation (coIP) and mass spectrometry revealed that hybrid TvTIM is formed with the compositional variations of paralogs. Single-particle electron microscopy for the 132-kDa purified TvTIM revealed the presence of a single ring of small Tims complex, while mitochondrial TIM22 complex bears twin small Tims hexamer. TvTIM is currently the only TIM visualized outside of Opisthokonta, which raised the question of which form is prevailing across eukaryotes. The tight association of the hybrid TvTIM with ADP/ATP carriers (AAC) suggests that AAC may directly supply ATP for the protein import since ATP synthesis is limited in hydrogenosomes.ConclusionsThe hybrid TvTIM in hydrogenosomes represents an original structural solution that evolved for protein import when Δψ is negligible and remarkable example of evolutionary adaptation to an anaerobic lifestyle.

Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals

BackgroundElephant seals exhibit extreme hypoxemic tolerance derived from repetitive hypoxia/reoxygenation episodes they experience during diving bouts. Real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture model from elephant seals and used RNA-seq, functional assays, and confocal microscopy to assess the molecular response to prolonged hypoxia.ResultsSeal and human endothelial cells exposed to 1% O2 for up to 6 h respond differently to acute and prolonged hypoxia. Seal cells decouple stabilization of the hypoxia-sensitive transcriptional regulator HIF-1α from angiogenic signaling. Rapid upregulation of genes involved in glutathione (GSH) metabolism supports the maintenance of GSH pools, and intracellular succinate increases in seal but not human cells. High maximal and spare respiratory capacity in seal cells after hypoxia exposure occurs in concert with increasing mitochondrial branch length and independent from major changes in extracellular acidification rate, suggesting that seal cells recover oxidative metabolism without significant glycolytic dependency after hypoxia exposure.ConclusionsWe found that the glutathione antioxidant system is upregulated in seal endothelial cells during hypoxia, while this system remains static in comparable human cells. Furthermore, we found that in contrast to human cells, hypoxia exposure rapidly activates HIF-1 in seal cells, but this response is decoupled from the canonical angiogenesis pathway. These results highlight the unique mechanisms that confer extraordinary tolerance to limited oxygen availability in a champion diving mammal.

PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.

Oxygen sensors enable cells to adapt to limited oxygen availability (hypoxia), affecting various cellular and tissue responses. Prolyl-4-hydroxylase domain 1-3 (PHD1-3; also called Egln1-3, HIF-P4H 1-3, HIF-PH 1-3) proteins belong to the Fe2+- and 2-oxoglutarate-dependent dioxygenase superfamily and utilise molecular oxygen (O2) alongside 2-oxoglutarate as co-substrate to hydroxylate two proline residues of α subunits of the dimeric hypoxia inducible factor (HIF) transcription factor. PHD1-3-mediated hydroxylation of HIF-α leads to its degradation and inactivation. Recently, various PHD inhibitors (PHI) have entered the clinics for treatment of renal anaemia. Pre-clinical analyses indicate that PHI treatment may also be beneficial in numerous other hypoxia-associated diseases. Nonetheless, the underlying molecular mechanisms of the observed protective effects of PHIs are only partly understood, currently hindering their translation into the clinics. Moreover, the PHI-mediated increase of Epo levels is not beneficial in all hypoxia-associated diseases and PHD-selective inhibition may be advantageous. Here, we summarise the current knowledge about the relevance and function of each of the three PHD isoforms in vivo, based on the deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents. This information is crucial for our understanding of the physiological relevance and function of the PHDs as well as for elucidating their individual impact on hypoxia-associated diseases. Furthermore, this knowledge highlights which diseases may best be targeted by PHD isoform-selective inhibitors in case such pharmacologic substances become available.

The properties of sustainable aviation fuel II: Laminar flame speed

This work reports on the study of flame characteristics and laminar flame speeds (LFS) of sustainable aviation fuel (SAF) and conventional fuels (Jet-A1 and JP-5) premixed with air at elevated pressures. The experimental facilities included the constant volume combustion chamber (CVCC) and used a shadowgraph system to quantify the LFS. The effects of equivalence ratio and ambient pressure on the flame speeds were examined by varying the initial pressure 1, 2, and 3 bar (in addition to 0.1 and 0.5 bar for flame morphology) and the equivalence ratio from 0.8 to 1.8 at 423 K of temperature. The results indicated that JP-5 had the highest LFS value (90.1 cm/s) compared to the other two fuels. Jet-A1 and SAF have the same LFS result, which is less than a 15% difference, excluding the high equivalence ratio and initial pressure. The higher the initial pressure, the lower the LFS for all conditions. The equivalence ratio of 1.2 resulted in the highest LFSs. In addition, in order to understand the laminar flame speed of SAF and its combustion chemical kinetics. Therefore, the sensitivity analysis of SAF was performed. Results indicated that the chain branching reaction (O2 + HOH + O) positively enhanced flame speed as equivalence ratios (φ) increased, while chain propagation reactions, notably O2 + HHO2 (+M), had a negative effect on flame speed, particularly diminishing their influence at higher φ due to limited oxygen availability.

Genomic insights into Yak (Bos grunniens) adaptations for nutrient assimilation in high-altitudes

High-altitude environments present formidable challenges for survival and reproduction, with organisms facing limited oxygen availability and scarce nutrient resources. The yak (Bos grunniens), indigenous to the Tibetan Plateau, has notably adapted to these extreme conditions. This study delves into the genomic basis of the yak’s adaptation, focusing on the positive selection acting on genes involved in nutrient assimilation pathways. Employing techniques in comparative genomics and molecular evolutionary analyses, we selected genes in the yak that show signs of positive selection associated with nutrient metabolism, absorption, and transport. Our findings reveal specific genetic adaptations related to nutrient metabolism in harsh climatic conditions. Notably, genes involved in energy metabolism, oxygen transport, and thermoregulation exhibited signs of positive selection, suggesting their crucial role in the yak’s successful colonization of high-altitude regions. The study also sheds light on the yak's immune system adaptations, emphasizing genes involved in response to various stresses prevalent at elevated altitudes. Insights into the yak’s genomic makeup provide valuable information for understanding the broader implications of high-altitude adaptations in mammalian evolution. They may contribute to efforts in enhancing livestock resilience to environmental challenges.

Looking deeper into the effects of scouring and aeration on membrane aerated biofilms: Analysis of nitrogen conversion, oxygen profiles and nitrous oxide emissions

This study investigated the effects of aeration and scouring strategies on the performance of Membrane Aerated Biofilm Reactors (MABRs) and the distribution of oxygen and nitrous oxide in the biofilm. Four flat sheet MABRs were operated with synthetic feed under different conditions: two with intermittent aeration (iMABR) and two with continuous aeration (cMABR). Scouring was induced by bubbling dinitrogen gas through the reactor bulk at low and high frequencies (LF and HF). In the iMABRs, a partial nitritation biofilm initially developed, but the biofilm adapted to the aeration strategy over time and became nitrifying. The cMABRs directly developed a nitrifying biofilm without a significant phase of partial nitritation. Limiting oxygen availability improved the overall performance with regards to total nitrogen (TN) removal by providing a better environment for anaerobic ammonium oxidation (Anammox) while limiting complete nitrification.Oxygen profiles were measured in the iMABR over time at different biofilms depths, showing that intermittent aeration led to various oxygen concentrations and temporal variations in the oxygen availabilities at different depths of the biofilm. Also, N2O emissions from the MABRs differed greatly between the different systems, but still remained lower compared to other reactor configurations for nitrogen removal, making the MABR technology a worthy alternative. The results showed large differences between the operating strategies of the MABRs and can help to gain more insight into the specific properties of MABRs for nitrogen removal.

Mathematical model of oxygen, nutrient, and drug transport in tuberculosis granulomas.

Physiological abnormalities in pulmonary granulomas-pathological hallmarks of tuberculosis (TB)-compromise the transport of oxygen, nutrients, and drugs. In prior studies, we demonstrated mathematically and experimentally that hypoxia and necrosis emerge in the granuloma microenvironment (GME) as a direct result of limited oxygen availability. Building on our initial model of avascular oxygen diffusion, here we explore additional aspects of oxygen transport, including the roles of granuloma vasculature, transcapillary transport, plasma dilution, and interstitial convection, followed by cellular metabolism. Approximate analytical solutions are provided for oxygen and glucose concentration, interstitial fluid velocity, interstitial fluid pressure, and the thickness of the convective zone. These predictions are in agreement with prior experimental results from rabbit TB granulomas and from rat carcinoma models, which share similar transport limitations. Additional drug delivery predictions for anti-TB-agents (rifampicin and clofazimine) strikingly match recent spatially-resolved experimental results from a mouse model of TB. Finally, an approach to improve molecular transport in granulomas by modulating interstitial hydraulic conductivity is tested in silico.

The HIF-1α/EGF/EGFR Signaling Pathway Facilitates the Proliferation of Yak Alveolar Type II Epithelial Cells in Hypoxic Conditions.

The yak is a unique creature that thrives in low-oxygen environments, showcasing its adaptability to high-altitude settings with limited oxygen availability due to its unique respiratory system. However, the impact of hypoxia on alveolar type II (AT2) epithelial cell proliferation in yaks remains unexplored. In this study, we investigated the effects of different altitudes on 6-month-old yaks and found an increase in alveolar septa thickness and AT2 cell count in a high-altitude environment characterized by hypoxia. This was accompanied by elevated levels of hypoxia-inducible factor-1α (HIF-1α) and epidermal growth factor receptor (EGFR) expression. Additionally, we observed a significant rise in Ki67-positive cells and apoptotic lung epithelial cells among yaks inhabiting higher altitudes. Our in vitro experiments demonstrated that exposure to hypoxia activated HIF-1α, EGF, and EGFR expression leading to increased proliferation rates among yak AT2 cells. Under normal oxygen conditions, activation of HIF-1α enhanced EGF/EGFR expressions which subsequently stimulated AT2 cell proliferation. Furthermore, activation of EGFR expression under normoxic conditions further promoted AT2 cell proliferation while simultaneously suppressing apoptosis. Conversely, inhibition of EGFR expression under hypoxic conditions had contrasting effects. In summary, hypoxia triggers the proliferation of yak AT2 cells via activation facilitated by the HIF-1α/EGF/EGFR signaling cascade.

Hypoxia-adenosine axis as therapeutic targets for acute respiratory distress syndrome.

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially important for conditions that involve tissue hypoxia, such as acute respiratory distress syndrome (ARDS), which globally poses significant health challenges without specific treatment options. Consequently, pharmacological strategies to amplify HIF-mediated adenosine production and receptor signaling are of great importance.

Spatiotemporal oxygen dynamics in young leaves reveal cyclic hypoxia in plants

Oxygen is essential for plant growth and development. Hypoxia occurs in plants due to limited oxygen availability following adverse environmental conditions as well in hypoxic niches in otherwise normoxic environments. However, the existence and functional integration of spatiotemporal oxygen dynamics with plant development remains unknown. In animal systems dynamic fluctuations in oxygen availability are known as cyclic hypoxia. In this study, we demonstrate that cyclic fluctuations in internal oxygen levels occur in young emerging leaves of Arabidopsis plants. Cyclic hypoxia in plants is based on a mechanism requiring the ETHYLENE RESPONSE FACTORS type VII (ERFVII) that are central components of the oxygen-sensing machinery in plants. The ERFVII-dependent mechanism allows precise adjustment of leaf growth in response to carbon status and oxygen availability within plant cells. This study thus establishes a functional connection between internal spatiotemporal oxygen dynamics and developmental processes of plants.

‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database

BackgroundIn the era of rationally designed synthetic biology, heterologous metabolites production, and other counter-nature engineering of cellular metabolism, we took a step back and recalled that ‘Mother(-Nature) knows best’. While still aiming at synthetic, non-natural outcomes of generating an ‘over-production phenotype’ we dug into the pre-designed transcriptional programs evolved in our host organism—Yarrowia lipolytica, hoping that some of these fine-tuned orchestrated programs could be hijacked and used. Having an interest in the practical outcomes of the research, we targeted industrially-relevant functionalities—stress resistance and enhanced synthesis of proteins, and gauged them over extensive experimental design’s completion.ResultsTechnically, the problem was addressed by screening a broad library of over 120 Y. lipolytica strains under 72 combinations of variables through a carefully pre-optimized high-throughput cultivation protocol, which enabled actual phenotype development. The abundance of the transcription program elicitors—transcription factors (TFs), was secured by their overexpression, while challenging the strains with the multitude of conditions was inflicted to impact their activation stratus. The data were subjected to mathematical modeling to increase their informativeness.The amount of the gathered data prompted us to present them in the form of a searchable catalog – the YaliFunTome database (https://sparrow.up.poznan.pl/tsdatabase/)—to facilitate the withdrawal of biological sense from numerical data. We succeeded in the identification of TFs that act as omni-boosters of protein synthesis, enhance resistance to limited oxygen availability, and improve protein synthesis capacity under inorganic nitrogen provision.ConclusionsAll potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest.