Oxygen Fluctuations Research Articles

Seasonal dissolved oxygen depletion in bottom waters may be linked to bioluminescence in a shallow Caribbean bay

Worldwide, coastal areas are susceptible to low dissolved oxygen (DO) concentrations due to anthropogenic activities. In the Caribbean, some regions are experiencing extreme incidences of hypoxia and anoxia, jeopardizing biodiversity in these ecosystems. Nonetheless, limited information about these dissolved oxygen fluctuations is available. Using continuous and discrete approaches, the temporal and spatial patterns of DO were examined at Bahia Fosforescente (BF) in southwestern Puerto Rico during 2018. The principal aim was to evaluate whether hypoxic/anoxic conditions are sustained, linked to rainfall, and correspond to bioluminescence fluctuations at BF. An oxycline below 3-m depth was found, reaching hypoxia/anoxia during the wet season when calmer winds dominate and achieve high bioluminescence levels. These results may suggest the incoming of nutrients and organic carbon during the wet season, favoring the development of near-bottom anoxic conditions and benthic nutrient fluxes that favor the growth of bioluminescent plankton such as Pyrodinium bahamense. DO levels in BF might be influenced by changes in climate patterns, which may profoundly affect local planktonic species, impacting the development of bioluminescent natural events and, thus, the local tourism activities that evolve around these natural events.

Hypoxia stress induces complicated miRNA responses in the gill of Chinese mitten crab (Eriocheir sinensis)

Hypoxia caused by global climate change and human activities has become a growing concern eliciting serious damages to aquatic animals. microRNAs (miRNAs) as non-coding regulatory RNAs exert vital effects on hypoxia responses. Chinese mitten crab (Eriocheir sinensis) with the habitat on the sediment surface or the pond bottom is susceptible to oxygen deficiency. However, whether miRNAs are involved in the response of the crabs to hypoxia stress remains enigmas. In this study, we conducted the whole transcriptome-based miRNA-mRNA integrated analysis of Chinese mitten crab gill under hypoxic condition for 3 h and 24 h We found that the acute hypoxia induces complex miRNA responses with the extensive influences on their target genes that engaged in various bio-processes, especially those associated with immunity, metabolism and endocrine. The impact of hypoxia on crab miRNAs is severer, as the exposure lasts longer. In response to the dissolved oxygen fluctuation, the HIF-1 signaling is activated by miRNAs to cope with the hypoxia stress through strategies including balancing inflammatory and autophagy involved in immunity, changing metabolism to reducing energy consumption, and enhancing oxygen-carrying and delivering capacities. The miRNAs and their corresponding target genes engaged in hypoxia response were intertwined into an intricate network. Moreover, the top hub molecular, miR-998-y and miR-275-z, discovered from the network might serve as biomarkers for hypoxia response in crabs. Our study provides the first systemic miRNA profile of Chinese mitten crab induced by hypoxia stress, and the identified miRNAs and the interactive network add new insights into the mechanism of hypoxia response in crabs.

Improving the chronostratigraphic framework of the Transvaal Supergroup (South Africa) through in-situ and high-precision U-Pb geochronology

The Transvaal Supergroup, on the Kaapvaal Craton in South Africa, is widely accepted as one of the best-preserved sedimentary archives to constrain planetary-scale environmental changes during the late Archean and early Proterozoic, yet the sedimentation age for certain stratigraphic intervals remains poorly constrained. To improve the temporal control on some of the first-order global changes recorded in these rocks, we carried out U-Pb analyses of detrital zircon populations from several clastic and volcano-clastic sedimentary units of the Transvaal Supergroup. We applied the Chemical Abrasion-Isotope Dilution-Thermal Ionization Mass Spectrometry (CA-ID-TIMS) technique on detrital and volcanic zircon populations that had been previously screened using the Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) technique. We report new maximum depositional age estimates for the Pannetjie (2456.6 ± 7.0 Ma), the Heynskop (2451.5 ± 2.5 Ma), the Makganyene (2423.1 ± 1.0 Ma) and the Hekpoort formations (2248.0 ± 1.1 Ma).A ca. 2.25 Ga-old cluster of LA-ICP-MS analyses in the Makganyene Formation was identified to be spurious, since it was completely removed during the chemical abrasion. Thus, we speculate that circulation of hydrothermal fluids and associated Pb-loss from a radiation-damaged lattice during the emplacement of the much younger Hekpoort Formation or possibly the Ophthalmia Orogeny, recorded in Western Australia, may have reset the U-Pb system of this zircon population. This implies that the accurate maximum depositional age of the Makganyene Formation is ca. 2.42 Ga instead, which denotes the age of the oldest glacial event of global extent during the Paleoproterozoic. Therefore, we suggest that the combination of both dating techniques is essential to ensure accurate maximum depositional age constraints for ancient detrital sedimentary rocks. Additionally, our data provides temporal constraints on a period characterized by major fluctuations in atmospheric oxygen. Finally, and supporting the complex nature of the Paleoproterozoic, linkages between widespread glaciations and atmospheric oxygen fluctuations remain to be explored.

EIF4EHP promotes Ldh mRNA translation in and fruit fly adaptation to hypoxia.

Hypoxia induces profound modifications in the gene expression program of eukaryotic cells due to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One significant consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. Drosophila melanogaster is strongly resistant to oxygen fluctuations; however, the mechanisms allowing specific mRNA to be translated into hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated into hypoxia by a mechanism involving a CA-rich motif present in its 3' untranslated region. Furthermore, we identified the cap-binding protein eIF4EHP as a main factor involved in 3'UTR-dependent translation under hypoxia. In accordance with this observation, we show that eIF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to LDH production and Drosophila adaptation to oxygen variations.

Benthic foraminiferal response to the Oceanic Anoxic Event 2 (Late Cretaceous) and evidence of bottom water re‐oxygenation during the Plenus Cold Event at Clot Chevalier (Vocontian Basin, SE France)

The Cenomanian-Turonian boundary interval is characterized by environmental perturbations related to the Oceanic Anoxic Event 2 (OAE 2) that severely affected the marine biota, including benthic and planktonic foraminifera. We present a continuous high-resolution benthic foraminiferal record in combination with published planktonic foraminiferal and geochemical data across the Cenomanian-Turonian boundary interval in the Clot Chevalier section (Vocontian Basin, SE France) with the aim to interpret paleoceanographic changes in bottom waters. Benthic foraminiferal assemblages are characterized by low diversity and indicate an outer shelf-upper bathyal environment. Changes in composition and abundance of the benthic assemblages throughout the stratigraphic section allow identification of seven distinct environments. In the middle Cenomanian, below the OAE 2, benthic foraminifera show high species diversity and abundance of infaunal and epifaunal taxa, suggesting an environment characterized by oxic conditions at the seafloor. The microfossil assemblages in the upper Cenomanian within the OAE 2 interval are dominated by radiolaria (> 50%) followed by benthic calcareous taxa (Gavelinella sp., Gyroidinoides sp., Praebulimina elata, Tappanina laciniosa). Benthic agglutinated taxa (Ammobaculites sp., Ammodiscus cretaceus, Gaudryina sp., Textulariopsis bettenstaedti) show high abundance in the lowest part of the OAE 2 and disappear close to the top of the interval. The assemblage composition and the highest values of Total Organic Carbon (TOC) registered in this interval suggest eutrophication and suboxic conditions at the seafloor. However, at ∼1 m above the onset of the OAE 2, the repopulation by inferred oxic benthic foraminiferal taxa (i.e., Frondicularia sp. and Ramulina aculeata) suggests ventilation of bottom water masses, recording the Plenus Cold Event (PCE). In the lowermost Turonian, the assemblages exhibit high species diversity and abundance with the re-appearance of calcareous taxa, indicating oxic conditions, and of agglutinated taxa associated to moderate oxygen concentrations. Results show that the distribution of benthic foraminifera follows fluctuations in oxygenation and carbon export flux at the seafloor interpreted as the environmental changes associated to the onset of the OAE 2 and of the PCE across the Cenomanian-Turonian boundary interval.

Scale-down of oxygen and glucose fluctuations in a tubular photobioreactor operated under oxygen-balanced mixotrophy.

Oxygen-balanced mixotrophy (OBM) is a novel type of microalgal cultivation that improves autotrophic productivity while reducing aeration costs and achieving high biomass yields on substrate. The scale-up of this process is not straightforward, as non-ideal mixing in large photobioreactors might have unwanted effects in cell physiology. We simulated at lab scale dissolved oxygen and glucose fluctuations in a tubular photobioreactor operated under OBM where glucose is injected at the beginning of the tubular section. We ran repeated batch experiments with the strain Galdieria sulphuraria ACUF 064 under glucose pulse feeding of different lengths, representing different retention times: 112, 71 and 21 minutes. During the long and medium tube retention time simulations, dissolved oxygen was depleted 15 to 25 minutes after every glucose pulse. These periods of oxygen limitation resulted in the accumulation of coproporphyrin III in the supernatant, an indication of disruption in the chlorophyll synthesis pathway. Accordingly, the absorption cross section of the cultures decreased steeply, going from values of 150 - 180 m2 ·kg-1 at the end of the first batch down to 50 - 70 m2 ·kg-1 in the last batches of both conditions. In the short tube retention time simulation, dissolved oxygen always stayed above 10% air saturation and no pigment reduction nor coproporphyrin III accumulation were observed. Concerning glucose utilization efficiency, glucose pulse feeding caused a reduction of biomass yield on substrate in the range of 4 to 22% compared to the maximum levels previously obtained with continuous glucose feeding (0.9 C-g·C-g-1 ). The missing carbon was excreted to the supernatant as extracellular polymeric substances constituted by carbohydrates and proteins. Overall, the results point out the importance of studying large-scale conditions in a controlled environment and the need for a highly controlled glucose feeding strategy in the scale-up of mixotrophic cultivation. This article is protected by copyright. All rights reserved.

Disturbance of primary producer communities disrupts the thermal limits of the associated aquatic fauna

Environmental fluctuation forms a framework of variability within which species have evolved. Environmental fluctuation includes predictability, such as diel cycles of aquatic oxygen fluctuation driven by primary producers. Oxygen availability and fluctuation shape the physiological responses of aquatic animals to warming, so that, in theory, oxygen fluctuation could influence their thermal ecology. We describe annual oxygen variability in agricultural drainage channels and show that disruption of oxygen fluctuation through dredging of plants reduces the thermal tolerance of freshwater animals. We compared the temperature responses of snails, amphipods, leeches and mussels exposed to either natural oxygen fluctuation or constant oxygen in situ under different acclimation periods. Oxygen saturation in channel water ranged from c. 0 % saturation at night to >300 % during the day. Temperature showed normal seasonal variation and was almost synchronous with daily oxygen fluctuation. A dredging event in 2020 dramatically reduced dissolved oxygen variability and the correlation between oxygen and temperature was lost. The tolerance of invertebrates to thermal stress was significantly lower when natural fluctuation in oxygen availability was reduced and decoupled from temperature. This highlights the importance of natural cycles of variability and the need to include finer scale effects, including indirect biological effects, in modelling the ecosystem-level consequences of climate change. Furthermore, restoration and management of primary producers in aquatic habitats could be important to improve the thermal protection of aquatic invertebrates and their resistance to environmental variation imposed by climate change.

Spatiotemporal variability of dissolved oxygen in response to morphological state in a central California coast bar-built estuary

Bar-built estuaries (BBEs) or intermittently closed/open lagoons (ICOLs) are common to coastal regions experiencing episodic river flows and seasonal precipitation changes along the US West Coast. Unique to Mediterranean climates, BBEs have a hydrologic mixing regime and variation in water chemistry characteristics resulting from seasonal breaches and closures of their mouth and watershed inputs. This study observes spatiotemporal variability in dissolved oxygen (DO) in a small bar-built estuary in Carmel, CA during variable morphological states. For this study, field measurements were collected using dissolved oxygen loggers during a seasonal transition from fully open to fully closed states to determine the spatiotemporal variability of dissolved oxygen within the three main branches of Carmel River Lagoon. The data collected spanned a 6-month (February to August 2020) period, covering several transitions from fully open to intermittently closed to fully closed mouth state. This study did not document any periods within the lagoon when dissolved oxygen concentrations were uniformly below water quality objective levels (5 mg/L) suggesting that during the entire period of this investigation, portions of the lagoon supported high oxygen conditions while also supporting a variety of other water chemistry characteristic zones, unique to BBEs. The dissolved oxygen fluctuations were closely tied to the temporal effects of environmental forcing (river discharge) on the seasonal transition of river mouth morphological state from fully open to fully closed. The main conclusion is that during open mouth states, relative DO variability in the bottom of the main channel is low and more similar to surface waters, indicating mixing, and during closed mouth states vertical location in the water column matters more. Furthermore, variability between sites suggests single point observations of DO cannot accurately represent the distribution of DO within a BBE.

A simple mathematical model of cyclic hypoxia and its impact on hypofractionated radiotherapy.

There is evidence that the population of cells that experience fluctuating oxygen levels ("acute," or, "cyclic" hypoxia) are more radioresistant than chronically hypoxic ones and hence, this population may determine radiotherapy (RT) response, in particular for hypofractionated RT, where reoxygenation may not be as prominent. A considerable effort has been devoted to examining the impact of hypoxia on hypofractionated RT; however, much less attention has been paid to cyclic hypoxia specifically and the role its kinetics may play in determining the efficacy of these treatments. Here, a simple mathematical model of cyclic hypoxia and fractionation effects was worked out to quantifythis. Cancer clonogen survival fraction was estimated using the linear quadratic model, modified to account for oxygen enhancement effects. An analytic approximation for oxygen transport away from a random network of capillaries with fluctuating oxygen levels was used to model inter-fraction tissue oxygen kinetics. The resulting survival fraction formula was used to derive an expression for the iso-survival biologically effective dose (BED), BEDiso-SF . These were computed for some common extra-cranial hypofractionated RTregimens. Using relevant literature parameter values, inter-fraction fluctuations in oxygenation were found to result in an added 1-2 logs of clonogen survival fraction in going from five fractions to one for the same nominal BED (i.e., excluding the effects of oxygen levels on radiosensitivity). BEDiso-SF 's for most ultra-hypofractionated (five or fewer fractions) regimens in a given tumor site are similar in magnitude, suggesting iso-efficacy for common fractionationschedules. Although significant, the loss of cell-killing with increasing hypofractionation is not nearly as large as previous estimates based on the assumption of complete reoxygenation between fractions. Most ultra-hypofractionated regimens currently in place offer sufficiently high doses to counter this loss of cell killing, although care should be taken in implementing single-fractionregimens.

Resilience and phenotypic plasticity of Arctic char (Salvelinus alpinus) facing cyclic hypoxia: insights into growth, energy stores and hepatic metabolism.

Arctic char (Salvelinus alpinus) is facing the decline of its southernmost populations due to several factors including rising temperatures and eutrophication. These conditions are also conducive to episodes of cyclic hypoxia, another possible threat to this species. In fact, lack of oxygen and reoxygenation can both have serious consequences on fish as a result of altered ATP balance and an elevated risk of oxidative burst. Thus, fish must adjust their phenotype to survive and equilibrate their energetic budget. However, their energy allocation strategy could imply a reduction in growth which could be deleterious for their fitness. Although the impact of cyclic hypoxia is a major issue for ecosystems and fisheries worldwide, our knowledge on how salmonid deal with high oxygen fluctuations remains limited. Our objective was to characterize the effects of cyclic hypoxia on growth and metabolism in Arctic char. We monitored growth parameters (specific growth rate, condition factor), hepatosomatic and visceral indexes, relative heart mass and hematocrit of Arctic char exposed to 30days of cyclic hypoxia. We also measured the hepatic protein synthesis rate, hepatic triglycerides as well as muscle glucose, glycogen and lactate and quantified hepatic metabolites during this treatment. The first days of cyclic hypoxia slightly reduce growth performance with a downward trend in specific growth rate in mass and condition factor variation compared to the control group. This acute exposure also induced a profound metabolome reorganization in the liver with an alteration of amino acid, carbohydrate and lipid metabolisms. However, fish rebalanced their metabolic activities and successfully maintained their growth and energetic reserves after 1month of cyclic hypoxia. These results demonstrate the impressive ability of Arctic char to cope with its changing environment but also highlight a certain vulnerability of this species during the first days of a cyclic hypoxia event.

Intravenous infusion of methylene blue to visualize the ureter in laparoscopic colorectal surgery

Objective: Intraoperative localization of the ureter can contribute to accurate dissection and minimize ureteral injury in colorectal surgery. We aim to summarize a single center's experience of fluorescence ureteral visualization using methylene blue (MB) and explore its visualization efficiency. Methods: This is a descriptive case-series-study. Clinical data of patients who had undergone laparoscopic colorectal surgery and fluorescence visualization of the ureter in the Gastrointestinal Surgery Department of Guangdong Provincial People's Hospital from March 2022 to May 2022 were retrospectively collected. Patients with incomplete surgery videos, renal insufficiency, or allergic reactions were excluded. MB was infused with 0.9% NaCl at 1.0 mg/kg in 100 mL of normal saline for 5 to 15 minutes during laparoscopic exploration. Imaging was performed using a device developed in-house by OptoMedic (Guangdong, China) that operates at 660nm to achieve excitation of MB. Clinical information, MB dosage, rate of successful fluorescence, time to fluorescence, operation time, blood loss, intraoperative blood oxygen levels, pathological staging, changes in renal function, and post-operative complications were retrospectively analyzed. Results: The study cohort comprised 27 patients (24 men and 3 women) with an average age of (60.25±16.95) years and an average body mass index of (21.72±3.42) kg/m2. The dosage of MB was 0.3-1.0 mg/kg and the infusion time was 5-15 minutes. Fluorescence signals were detected in all patients. The median time to signal detection was 20 (range, 10 to 40) minutes after MB infusion. The range of intraoperative blood oxygen fluctuation averaged 2.5% (range, 0 to 7.0%). The median change in creatine concentration was -1.3 (range, -17.2 to 29.2) µmol/L. No patients had complications associated with use of MB. Fluorescence visualization of the ureter was very valuable clinically in two patients (thick mesentery, stage T4). Conclusion: MB is a safe and effective means of visualizing the ureter by fluorescence during laparoscopic colorectal surgery, especially when the procedure is difficult. MB in a dosage of less than 1 mg/kg can slowly infused for more than 5 minutes during laparoscopic exploration. During the infusion, attention must be paid to blood oxygen fluctuations.

S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.

Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and Friedreich’s ataxia.

Effect of Atmospheric Conditions on Pathogenic Phenotypes of Arcobacter butzleri.

Arcobacter butzleri is an emergent gram-negative enteropathogenic bacterium widespread in different environments and hosts. During the colonization of the gastrointestinal tract, bacteria face a variety of environmental conditions to successfully establish infection in a new host. One of these challenges is the fluctuation of oxygen concentrations encountered not only throughout the host gastrointestinal tract and defences but also in the food industry. Oxygen fluctuations can lead to modulations in the virulence of the bacterium and possibly increase its pathogenic potential. In this sense, eight human isolates of A. butzleri were studied to evaluate the effects of microaerobic and aerobic atmospheric conditions in stressful host conditions, such as oxidative stress, acid survival, and human serum survival. In addition, the effects on the modulation of virulence traits, such as haemolytic activity, bacterial motility, biofilm formation ability, and adhesion and invasion of the Caco-2 cell line, were also investigated. Overall, aerobic conditions negatively affected the susceptibility to oxygen reactive species and biofilm formation ability but improved the isolates' haemolytic ability and motility while other traits showed an isolate-dependent response. In summary, this work demonstrates for the first time that oxygen levels can modulate the potential pathogenicity of A. butzleri, although the response to stressful conditions was very heterogeneous among different strains.

Multi‐center study reveals impairment of cortical tissue oxygenation during rising blood CO2 tension in MCI and AD patients

AbstractBackgroundAn ongoing multi‐center study of a consortium of Alzheimer’s Disease Centers in Los Angeles (USC), Dallas (UT‐SWMC) and Kansas City (KUMC) has explored quantitatively the dynamics of the homeostatic mechanism that maintains adequate cortical tissue oxygenation during a rise in blood CO2 tension. The results from cognitively normal subjects and MCI/AD patients were compared to assess differences in the dynamics of this important homeostatic mechanism.MethodQuantification of the dynamics of cortical tissue oxygenation was achieved through extraction of predictive models from five‐minute data‐records of spontaneous fluctuations in cortical tissue oxygenation (CTO), measured non‐invasively via near infrared spectroscopy at the prefrontal cortex, and the associated fluctuations in arterial blood pressure (ABP) and end‐tidal CO2 (etCO2). Using a novel kernel‐based modeling methodology, we analyzed the time‐series data from 25 MCI patients, 7 AD patients and 45 age‐matched cognitively normal controls (NC) and obtained predictive models of the dynamic effects of ABP and etCO2 (viewed as a proxy for blood CO2 tension) upon CTO. These predictive models were used to quantify the dynamics of cortical CO2 reactivity (CCR) in each participant, as the time‐average of the model‐predicted CTO response to unit‐step etCO2 change over the first 30 sec. The obtained CCR indices were used to evaluate the differences between NC and MCI/AD patients.ResultThe obtained CCR indices were significantly different for the 32 patients (MCI and AD lumped together due to small number of AD) vs. 45 age‐matched controls (p= 0.0083), with respective mean (SD): 0.014 (0.108) vs ‐0.059 (0.119). This is illustrated in Figure 1, where the average model‐predicted CTO responses to a unit‐step change of etCO2 are shown for 32 MCI/AD patients (red line) and 45 controls (blue line). Note the negative values of the average CTO response for patients (red line) to unit‐step increase of etCO2 that indicates polarity reversal of the normal CO2 vasomotor reactivity (blue line).ConclusionQuantitative analysis of cortical oxygenation dynamics under resting spontaneous conditions in 32 MCI/AD patients relative to 45 age‐matched controls revealed a significant impairment of the homeostatic mechanism that maintains adequate oxygenation of cortical tissue during a rise in blood CO2 tension.

Effects of different oxygen regimes on ecological performance and bioenergetics of a coastal marine bioturbator, the soft shell clam Mya arenaria

Benthic species are exposed to oxygen fluctuations that can affect their performance and survival. Physiological effects and ecological consequences of fluctuating oxygen are not well understood in marine bioturbators such as the soft-shell clam Mya arenaria. We explored the effects of different oxygen regimes (21 days of exposure to constant hypoxia (~4.1 kPa PO2), cyclic hypoxia (~2.1–~10.4 kPa PO2) or normoxia (~21 kPa PO2)) on energy metabolism, oxidative stress and ecological behaviors (bioirrigation and bioturbation) of M. arenaria. Constant hypoxia and post-hypoxic recovery in cyclic hypoxia led to oxidative injury of proteins and lipids, respectively. Clams acclimated to constant hypoxia maintained aerobic capacity similar to the normoxic clams. In contrast, clams acclimated to cyclic hypoxia suppressed aerobic metabolism and activated anaerobiosis during hypoxia, and strongly upregulated aerobic metabolism during recovery. Constant hypoxia led to decreased lipid content, whereas in cyclic hypoxia proteins and glycogen accumulated during recovery and were broken down during the hypoxic phase. Digging of clams was impaired by constant and cyclic hypoxia, and bioirrigation was also suppressed under constant hypoxia. Overall, cyclic hypoxia appears less stressful for M. arenaria due to the metabolic flexibility that ensures recovery during reoxygenation and mitigates the negative effects of hypoxia, whereas constant hypoxia leads to depletion of energy reserves and impairs ecological functions of M. arenaria potentially leading to negative ecological consequences in benthic ecosystems.

Abnormal Regional Spontaneous Neural Activity and Functional Connectivity in Unmedicated Patients with Narcolepsy Type 1: A Resting-State fMRI Study.

Previous Resting-state functional magnetic resonance imaging (fMRI) studies have mainly focused on cerebral functional alteration in processing different emotional stimuli in patients with narcolepsy type 1 (NT1), but were short of exploration of characteristic brain activity and its remote interaction patterns. This study aimed to investigate the spontaneous blood oxygen fluctuations at rest and to elucidate the neural mechanisms underlying neuropsychiatric behavior. A total of 18 unmedicated patients with NT1 and matched healthy individuals were recruited in a resting-state fMRI study. Magnetic resonance imaging (MRI) data were first analyzed using fractional low-frequency amplitude of low-frequency fluctuation (fALFF) to detect changes in local neural activity, and regions with group differences were taken as regions of interest (ROIs). Secondly, functional connectivity (FC) analysis was used to explore altered connectivity between ROIs and other areas. Lastly, the relationship between functional brain activity and neuropsychiatric behaviors was analyzed with correlation analysis. fALFF analysis revealed enhanced neural activity in bilateral fusiform gyrus (FFG), right precentral gyrus, and left postcentral gyrus (PoCG) in the NT1 group. The patients indicated reduced activity in the bilateral temporal pole middle temporal gyrus (TPOmid), left caudate nucleus (CAU), left parahippocampus, left precuneus (PCUN), right amygdala, and right anterior cingulate and paracingulate gyri. ESS score was negatively correlated with fALFF in the right FFG. The NT1 group revealed decreased connectivity between left TPOmid and right PoCG, the bilateral middle frontal gyrus, left superior frontal gyrus, medial, and right supramarginal gyrus. Epworth Sleepiness Scale (ESS) was negatively correlated with FC of the left TPOmid with left putamen (PUT) in NT1. Compared with healthy controls (HCs), enhanced FC of the left CAU with right FFG was positively associated with MSLT-SOREMPs in patients. Furthermore, increased FC of the left PCUN with right PoCG was positively correlated with SDS score. We found that multiple functional activities related to the processing of emotional regulation and sensory information processing were abnormal, and some were related to clinical characteristics. fALFF in the left postcentral or right precentral gyrus may be used as a biomarker of narcolepsy, whereas fALFF in the right fusiform and the FC strength of the left temporal pole middle temporal gyrus with the putamen may be clinical indicators to assess the drowsiness severity of narcolepsy.

Effects of hypoxia and reoxygenation on mitochondrial functions and transcriptional profiles of isolated brain and muscle porcine cells

Oxygen fluctuations might occur in mammalian tissues under physiological (e.g. at high altitudes) or pathological (e.g. ischemia–reperfusion) conditions. Mitochondria are the key target and potential amplifiers of hypoxia-reoxygenation (H-R) stress. Understanding the mitochondrial responses to H-R stress is important for identifying adaptive mechanisms and potential therapeutic solutions for pathologies associated with oxygen fluctuations. We explored metabolic response to H-R stress in two tissue types (muscle and brain) with different degrees of hypoxia tolerance in a domestic pig Sus scrofa focusing on the cellular responses independent of the systemic regulatory mechanisms. Isolated cells from the skeletal muscle (masseter) and brain (thalamus) were exposed to acute short-term (15 min) hypoxia followed by reoxygenation. The mitochondrial oxygen consumption, reactive oxygen species (ROS) production rates and transcriptional profiles of hypoxia-responsive mRNA and miRNA were determined. Mitochondria of the porcine brain cells showed a decrease in the resting respiration and ATP synthesis capacity whereas the mitochondria from the muscle cells showed robust respiration and less susceptibility to H-R stress. ROS production was not affected by the short-term H-R stress in the brain or muscle cells. Transcriptionally, prolyl hydroxylase domain protein EGLN3 was upregulated during hypoxia and suppressed during reoxygenation in porcine muscle cells. The decline in EGLN3 mRNA during reoxygenation was accompanied by an upregulation of hypoxia-inducible factor subunit α (HIF1A) transcripts in the muscle cells. However, in the brain cells, HIF1A mRNA levels were suppressed during reoxygenation. Other functionally important transcripts and miRNAs involved in antioxidant response, apoptosis, inflammation, and substrate oxidation were also differentially expressed between the muscle and brain cells. Suppression of miRNA levels during acute intermittent hypoxia was stronger in the brain cells affecting ~ 55% of all studied miRNA transcripts than in the muscle cells (~ 25% of miRNA) signifying transcriptional derepression of the respective mRNA targets. Our study provides insights into the potential molecular and physiological mechanisms contributing to different hypoxia sensitivity of the studied tissues and can serve as a starting point to better understand the biological processes associated with hypoxia stress, e.g. during ischemia and reperfusion.

Rapid marine oxygen variability: Driver of the Late Ordovician mass extinction

The timing and connections between global cooling, marine redox conditions, and biotic turnover are underconstrained for the Late Ordovician. The second most severe mass extinction occurred at the end of the Ordovician period, resulting in ~85% loss of marine species between two extinction pulses. As the only "Big 5" extinction that occurred during icehouse conditions, this interval is an important modern analog to constrain environmental feedbacks. We present a previously unexplored thallium isotope records from two paleobasins that record global marine redox conditions and document two distinct and rapid excursions suggesting vacillating (de)oxygenation. The strong temporal link between these perturbations and extinctions highlights the possibility that dynamic marine oxygen fluctuations, rather than persistent, stable global anoxia, played a major role in driving the extinction. This evidence for rapid oxygen changes leading to mass extinction has important implications for modern deoxygenation and biodiversity declines.

First person – Andreas Enström

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Andreas Enström is first author on ‘ RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes’, published in BiO. Andreas is a PhD student in the lab of Gesine Paul at Lund University, Sweden, investigating cellular adaptations to fluctuations in oxygen and their implications.

Dietary-derived vitamin B12 protects Caenorhabditis elegans from thiol-reducing agents

BackgroundOne-carbon metabolism, which includes the folate and methionine cycles, involves the transfer of methyl groups which are then utilised as a part of multiple physiological processes including redox defence. During the methionine cycle, the vitamin B12-dependent enzyme methionine synthetase converts homocysteine to methionine. The enzyme S-adenosylmethionine (SAM) synthetase then uses methionine in the production of the reactive methyl carrier SAM. SAM-binding methyltransferases then utilise SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids.ResultsWe describe a novel SAM methyltransferase, RIPS-1, which was the single gene identified from forward genetic screens in Caenorhabditis elegans looking for resistance to lethal concentrations of the thiol-reducing agent dithiothreitol (DTT). As well as RIPS-1 mutation, we show that in wild-type worms, DTT toxicity can be overcome by modulating vitamin B12 levels, either by using growth media and/or bacterial food that provide higher levels of vitamin B12 or by vitamin B12 supplementation. We show that active methionine synthetase is required for vitamin B12-mediated DTT resistance in wild types but is not required for resistance resulting from RIPS-1 mutation and that susceptibility to DTT is partially suppressed by methionine supplementation. A targeted RNAi modifier screen identified the mitochondrial enzyme methylmalonyl-CoA epimerase as a strong genetic enhancer of DTT resistance in a RIPS-1 mutant. We show that RIPS-1 is expressed in the intestinal and hypodermal tissues of the nematode and that treating with DTT, β-mercaptoethanol, or hydrogen sulfide induces RIPS-1 expression. We demonstrate that RIPS-1 expression is controlled by the hypoxia-inducible factor pathway and that homologues of RIPS-1 are found in a small subset of eukaryotes and bacteria, many of which can adapt to fluctuations in environmental oxygen levels.ConclusionsThis work highlights the central importance of dietary vitamin B12 in normal metabolic processes in C. elegans, defines a new role for this vitamin in countering reductive stress, and identifies RIPS-1 as a novel methyltransferase in the methionine cycle.