Redox Shift Research Articles

Mitochondrial Redox Signaling Is Critical to the Normal Functioning of the Neuronal System.

Mitochondrial dysfunction often leads to neurodegeneration and is considered one of the main causes of neurological disorders, such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and other age-related diseases. Mitochondrial dysfunction is tightly linked to oxidative stress and accumulating evidence suggests the association between oxidative stress and neurological disorders. However, there is insufficient knowledge about the role of pro-oxidative shift in cellular redox and impairment of redox-sensitive signaling in the development of neurodegenerative pathological conditions. To gain a more complete understanding of the relationship between mitochondria, redox status, and neurodegenerative disorders, we investigated the effect of mitochondrial thiol-dependent peroxidases, peroxiredoxins (Prxs), on the physiological characteristics of flies, which change with pathologies such as PD, ALS and during aging. We previously found that through their ability to sense changes in redox and regulate redox-sensitive signaling, Prxs play a critical role in maintaining global thiol homeostasis, preventing age-related apoptosis and chronic activation of the immune response. We also found that the phenotype of flies under-expressing Prxs in mitochondria shares many characteristics with the phenotype of Drosophila models of neurological disorders such as ALS, including impaired locomotor activity and compromised redox balance. Here, we expanded the study and found that under-expression of mitochondrial Prxs leads to behavioral changes associated with neural function, including locomotor ability, sleep-wake behavior, and temperature-sensitive paralysis. We also found that under-expression of mitochondrial Prxs with a motor-neuron-specific driver, D42-GAL4, was a determining factor in the development of the phenotype of shortened lifespan and impaired motor activity in flies. The results of the study suggest a causal link between mitochondrial Prx activity and the development of neurological disorders and pre-mature aging.

Biochemical Basis for Redox Regulation of Chloroplast-Localized Phosphofructokinase from Arabidopsis thaliana.

Various proteins in plant chloroplasts are subject to thiol-based redox regulation, allowing light-responsive control of chloroplast functions. Most redox-regulated proteins are known to be reductively activated in the light in a thioredoxin (Trx)-dependent manner, but its regulatory network remains incompletely understood. Using a biochemical procedure, we here show that a specific form of phosphofructokinase (PFK) is a novel redox-regulated protein whose activity is suppressed upon reduction. PFK is a key enzyme in the glycolytic pathway. In Arabidopsis thaliana, PFK5 is targeted to chloroplasts and uniquely contains an insertion sequence harboring two Cys residues (Cys152 and Cys157) in the N-terminal region. Redox shift assays using a thiol-modifying reagent indicated that PFK5 is efficiently reduced by a specific type of Trx, namely, Trx-f. PFK5 enzyme activity was lowered with the Trx-f-dependent reduction. PFK5 redox regulation was bidirectional; PFK5 was also oxidized and activated by the recently identified Trx-like2/2-Cys peroxiredoxin pathway. Mass spectrometry-based peptide mapping analysis revealed that Cys152 and Cys157 are critical for the intramolecular disulfide bond formation in PFK5. The involvement of Cys152 and Cys157 in PFK5 redox regulation was further supported by a site-directed mutagenesis study. PFK5 catalyzes the reverse reaction of fructose 1,6-bisphosphatase (FBPase), which is reduced and activated specifically by Trx-f. Our data suggest that PFK5 redox regulation, together with that of FBPase, constitutes a checkpoint for switching light/dark metabolism in chloroplasts.

Reductive stress promotes protein aggregation and impairs neurogenesis

Redox homeostasis regulates key cellular signaling in both physiology and pathology. While perturbations result in shifting the redox homeostasis towards oxidative stress are well documented, the influence of reductive stress (RS) in neurodegenerative diseases and its mechanisms are unknown. Here, we postulate that a redox shift towards the reductive arm (through the activation of Nrf2 signaling) will damage neurons and impair neurogenesis. In proliferating and differentiating neuroblastoma (Neuro 2a/N2a) cells, sulforaphane-mediated Nrf2 activation resulted in increased transcription/translation of antioxidants and glutathione (GSH) production along with significantly declined ROS in a dose-dependent manner leading to a reductive-redox state (i.e. RS). Interestingly, this resulted in endoplasmic reticulum (ER) stress leading to subsequent protein aggregation/proteotoxicity in neuroblastoma cells. Under RS, we also observed elevated Tau/α-synuclein and their co-localization with other protein aggregates in these cells. Surprisingly, we noticed that acute RS impaired neurogenesis as evidenced from reduced neurite outgrowth/length. Furthermore, maintaining the cells in a sustained RS condition (for five consecutive generations) dramatically reduced their differentiation and prevented the formation of axons (p < 0.05). This impairment in RS mediated neurogenesis occurs through the alteration of Tau dynamics i.e. RS activates the pathogenic GSK3β/Tau cascade thereby promoting the phosphorylation of Tau leading to proteotoxicity. Of note, intermittent withdrawal of sulforaphane from these cells suppressed the proteotoxic insult and re-activated the differentiation process. Overall, this results suggest that either acute or chronic RS could hamper neurogenesis through GSK3β/TAU signaling and proteotoxicity. Therefore, investigations identifying novel redox mechanisms impacting proteostasis are crucial to preserve neuronal health.

Forced expression of miR-143 and -145 in cardiomyocytes induces cardiomyopathy with a reductive redox shift

BackgroundAnimal model studies show that reductive stress is involved in cardiomyopathy and myopathy, but the exact physiological relevance remains unknown. In addition, the microRNAs miR-143 and miR-145 have been shown to be upregulated in cardiac diseases, but the underlying mechanisms associated with these regulators have yet to be explored.MethodsWe developed transgenic mouse lines expressing exogenous miR-143 and miR-145 under the control of the alpha-myosin heavy chain (αMHC) promoter/enhancer.ResultsThe two transgenic lines showed dilated cardiomyopathy-like characteristics and early lethality with markedly increased expression of miR-143. The expression of hexokinase 2 (HK2), a cardioprotective gene that is a target of miR-143, was strongly suppressed in the transgenic hearts, but the in vitro HK activity and adenosine triphosphate (ATP) content were comparable to those observed in wild-type mice. In addition, transgenic complementation of HK2 expression did not reduce mortality rates. Although HK2 is crucial for the pentose phosphate pathway (PPP) and glycolysis, the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) was unexpectedly higher in the hearts of transgenic mice. The expression of gamma-glutamylcysteine synthetase heavy subunit (γ-GCSc) and the in vitro activity of glutathione reductase (GR) were also higher, suggesting that the recycling of GSH and its de novo biosynthesis were augmented in transgenic hearts. Furthermore, the expression levels of glucose-6-phosphate dehydrogenase (G6PD, a rate-limiting enzyme for the PPP) and p62/SQSTM1 (a potent inducer of glycolysis and glutathione production) were elevated, while p62/SQSTM1 was upregulated at the mRNA level rather than as a result of autophagy inhibition. Consistent with this observation, nuclear factor erythroid-2 related factor 2 (Nrf2), Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) were activated, all of which are known to induce p62/SQSTM1 expression.ConclusionsOverexpression of miR-143 and miR-145 leads to a unique dilated cardiomyopathy phenotype with a reductive redox shift despite marked downregulation of HK2 expression. Reductive stress may be involved in a wider range of cardiomyopathies than previously thought.

Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy.

CD8+ effector T (TE) cell proliferation and cytokine production depends on enhanced glucose metabolism. However, circulating T cells continuously adapt to glucose fluctuations caused by diet and inter-organ metabolite exchange. Here we show that transient glucose restriction (TGR) in activated CD8+ TE cells metabolically primes effector functions and enhances tumour clearance in mice. Tumour-specific TGR CD8+ TE cells co-cultured with tumour spheroids in replete conditions display enhanced effector molecule expression, and adoptive transfer of these cells in a murine lymphoma model leads to greater numbers of immunologically functional circulating donor cells and complete tumour clearance. Mechanistically, TE cells treated with TGR undergo metabolic remodelling that, after glucose re-exposure, supports enhanced glucose uptake, increased carbon allocation to the pentose phosphate pathway (PPP) and a cellular redox shift towards a more reduced state-all indicators of a more anabolic programme to support their enhanced functionality. Thus, metabolic conditioning could be used to promote efficiency of T-cell products for adoptive cellular therapy.

Faradaic effects in electrochemically gated graphene sensors in the presence of redox active molecules

Field-effect transistors (FETs) based on graphene are promising devices for the direct sensing of a range of analytes in solution. We show here that the presence of redox active molecules in the analyte solution leads to the occurrence of heterogeneous electron transfer with graphene generating a Faradaic current (electron transfer) in a FET configuration resulting in shifts of the Dirac point. Such a shift occurs if the Faradaic current is significantly high, e.g. due to a large graphene area. Furthermore, the redox shift based on the Faradaic current, reminiscent of a doping-like effect, is found to be non-Nernstian and dependent on parameters known from electrode kinetics in potentiodynamic methods, such as the electrode area, the standard potential of the redox probes and the scan rate of the gate voltage modulation. This behavior clearly differentiates this effect from other transduction mechanisms based on electrostatic interactions or molecular charge transfer doping effects, which are usually behind a shift of the Dirac point. These observations suggest that large-area unmodified/pristine graphene in field-effect sensors behaves as a non-polarized electrode in liquid. Strategies for ensuring a polarized interface are discussed.

Highly dynamic marine redox state through the Cambrian explosion highlighted by authigenic δ238U records

The history of oceanic oxygenation from the late Neoproterozoic to the early Cambrian is currently debated, making it difficult to gauge whether, and to what extent environmental triggers played a role in shaping the trajectory of metazoan diversification. Uranium isotope (δ238U) records from carbonates have recently been used to argue for significant swings in the global marine redox state from the late Neoproterozoic to the early Cambrian. However, geochemical signatures in carbonates—the U isotope archive most commonly employed to argue for redox shifts—are susceptible to diagenetic alteration and may have variable offsets from seawater values. Therefore, there is an impetus to reconstruct seawater U isotopic evolution using another sedimentary archive, in order to verify that these excursions can indeed be linked to global shifts in marine redox landscape. Here we report new U isotope data from two fine-grained siliciclastic upper Ediacaran to lower Cambrian (ca. 551–515 Ma) successions in South China. We find large δ238U swings between −0.63‰ and +0.39‰ for calculated values of authigenic U in the siliciclastic rocks, consistent with correlative records from the carbonates. The replication of these patterns in both carbonate and siliciclastic units provides confirmatory evidence that the early Cambrian seawater was characterized by highly variable U isotope compositions. These new δ238U data also provide higher-resolution records of global oceanic redox conditions during Cambrian Age 3, coeval with a critical interval of the Cambrian explosion. These δ238U data bolster the case that the Ediacaran-Cambrian transition experienced massive swings in marine redox state, providing a dynamic environmental backdrop for and potentially even a key driver of the emergence and radiation of metazoans.

139-LB: The Redox Balance Predicts Both Cardiovascular (CV) and Renal Outcomes in CANVAS

We tested whether circulating metabolites reflecting cytosolic (lactate/pyruvate) or mitochondrial (β-hydroxybutyrate/acetoacetate [AcAc]) redox balance are associated with major clinical outcomes in patients with type 2 diabetes. The CANVAS study randomized participants to placebo (Plb) or canagliflozin (100mg or 300mg) (Tx) and followed them for up to 6 years. Metabolic markers were measured at baseline (2,373 in Tx [dose combined] and 1,185 in Plb), at year 1 (2,022 in Tx and 949 in Plb) and year 2 (1,793 in Tx and 834 in Plb). By linear mixed model analysis, plasma free fatty acids, AcAc, and β-hydroxybutyrate increased with Tx vs. Plb, whereas plasma pyruvate decreased with Tx while glycerol and lactate did not change significantly. Of note, these changes were independent of the background antihyperglycemic medication (metformin, sulfonylureas, insulin, or combinations thereof). The incidence of hospitalized heart failure or cardiovascular death (HHF/CVD) was 10.2%, the incidence of the renal composite endpoint (CombR; i.e., 40% reduction in eGFR or renal replacement/death) was 3.9%. In Cox models adjusting for sex, age, BMI, HbA1c, baseline systolic blood pressure, diabetes duration, smoking, baseline use of diuretics or statins, history of heart failure, prior CV disease, and Tx, baseline AcAc was a negative predictor of HHF/CVD (HR=0.83 [95%CI 0.75-0.94]), while baseline lactate was a positive predictor (HR=1.42 [95%CI 1.20-1.68]). Adding baseline ACR and eGFR to the same multivariate model for CombR as the outcome, AcAc was still a negative (HR=0.84 [95%CI 0.75-0.94]) and lactate still a positive predictor (HR=1.42 [95%CI 1.20-1.67]). For CV and renal outcomes, higher baseline plasma lactate is an independent positive risk marker potentially reflecting a reducing cytosolic redox shift, but higher baseline plasma AcAc is a protective factor, which may be related to efficient mitochondrial supply/usage of reducing equivalents. Further analysis is needed to test these hypotheses. Disclosure E. Ferrannini: Consultant; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Oramed Pharmaceuticals. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc. S. Baldi: None. T. Scozzaro: None. F. Tesfaye: Employee; Self; Janssen Research &amp; Development, LLC. W. Shaw: Employee; Self; Janssen Pharmaceuticals, Inc. N. Rosenthal: None. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson &amp; Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. B. Neal: Research Support; Self; Janssen Research &amp; Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. V. Perkovic: Other Relationship; Self; See Other Relationship field. M.K. Hansen: Employee; Self; Janssen Research &amp; Development, LLC. Funding Janssen Research &amp; Development, LLC

Marine redox variability from Baltica during extinction events in the latest Ordovician–early Silurian

It is well documented that Upper Ordovician and Silurian successions record multiple marine turnover events – including the second-largest mass extinction in the Phanerozoic – widespread glaciation, and multiple global carbon cycle perturbations. Whereas causal mechanisms for the Late Ordovician major mass extinction event involving climate, paleoceanographic variation, and δ13C records have been published, similar records remain poorly constrained for subsequent extinction events in the early Silurian. Here, we present new organic matter carbon isotope (δ13Corg) chemostratigraphy and corresponding paleoredox proxies (Fe speciation, [Mn, V, Mo], and pyrite sulfur isotopes) from two organic-rich drill core sections in Sweden and Latvia that span the upper Katian through lower Wenlock stages (446–431 Ma). Pyritized Fe and bulk sedimentary Mn concentrations from Upper Ordovician strata in southern Sweden suggest a local redox shift to more reducing conditions in the late Hirnantian, possibly including euxinic (anoxic and sulfidic water column) conditions that coincide with the second mass extinction pulse. The new high-resolution δ13Corg and δ34Spyr datasets from the late Aeronian (early Silurian) interval within both drill cores show positive excursions that are broadly coincident with the associated Sandvika and sedgwickii extinction events. Independently, Fe speciation and bulk sedimentary trace metal data from this late Aeronian interval record locally euxinic conditions in both the deep basinal (Sweden) and distal shelf (Latvia) settings before and during the late Aeronian positive δ13C excursion. This multiproxy paleoredox dataset provides the first direct evidence for local to regional expansion of reducing marine conditions coincident with this early Silurian (late Aeronian) biotic event and positive δ13C excursion. Additionally, new δ34Spyr values spanning the Llandovery/Wenlock boundary interval in the Latvia core show a positive excursion coincident with Fe speciation and trace metal enrichments that imply a local redox perturbation with intermittently euxinic bottom waters during the rising limb of the Ireviken positive δ13C excursion. The combination of these geochemical data for local- to regional-scale (more data required for global interpretations) changes in marine redox conditions with paleobiological records and evidence for eustatic sea-level rise indicate that environmental stresses related to an expansion of anoxic to euxinic conditions were a probable driver for several extinction events during the latest Ordovician–early Silurian.

Selenite Sorption on Hydrated CEM-V/A Cement in the Presence of Steel Corrosion Products: Redox vs Nonredox Sorption.

Reinforced cementitious structures in nuclear waste repositories will act as barriers that limit the mobility of radionuclides (RNs) in case of eventual leakage. CEM-V/A cement, a ternary blended cement with blast furnace slag (BFS) and fly ash (FA), could be qualified and used in nuclear waste disposal. Chemical interactions between the cement and RNs are critical but not completely understood. Here, we combined wet chemistry methods, synchrotron-based X-ray techniques, and thermodynamic modeling to explore redox interactions and nonredox sorption processes in simulated steel-reinforced CEM-V/A hydration systems using selenite as a molecular probe. Among all of the steel corrosion products analyzed, only the addition of Fe0 can obviously enhance the reducing ability of cement toward selenite. In comparison, steel corrosion products showed stronger reducing power in the absence of cement hydrates. Selenium K-edge X-ray absorption spectroscopy (XAS) revealed that selenite immobilization mechanisms included nonredox inner-/outer-sphere complexations and reductive precipitations of FeSe and/or Se(0). Importantly, the hydrated pristine cement showed a good reducing ability, driven by ferrous phases and (bi)sulfides (as shown by sulfur K-edge XAS) originated from BFS and FA. The overall redox potential imposed by hydrated CEM-V/A was determined, hinting to a redox shift in underground cementitious structures.

Relationship between Optical Redox Status and Reactive Oxygen Species in Cancer Cells

Shifted NAD(H) redox status and enhanced reactive oxygen species (ROS) scavenging systems have been observed in cancers. However, how such redox shift is related to the ROS level in cancer cells is less clear. Based on collecting the intrinsic fluorescence of oxidized flavoproteins (Fp containing flavin adenine dinucleotide) and reduced nicotinamide adenine dinucleotide (NADH), optical redox imaging (ORI) provides a quantitative measure of the mitochondrial redox state by the optical redox ratio, Fp/(NADH+Fp), a surrogate marker of the NAD+-coupled redox state NAD+/NADH. Our study aims to explore the relationship between NAD(H) redox status and ROS by imaging NADH, Fp, and ROS levels using cultured breast cancer cell models. By manipulating either ROS levels via application of exogenous H2O2 or redox status via metabolic perturbation compounds, we found that: (1) oxidation of NAD(H) redox status correlates with ROS levels at lower H2O2 concentrations (up to ~700 μM), but not necessarily at higher concentrations; (2) an elevated ROS level diminishes NADH and reduces redox ratio plasticity; (3) either more oxidized or more reduced status can correlate to an increased ROS level; and (4) sometimes, a more oxidized status can correlate to a decreased ROS level depending on cell lines. These observations indicated that cellular NAD(H) redox state and ROS are intricately related but can also change separately. This study can benefit cancer research as both NAD(H) redox status and ROS have been implicated in cancer transformation and progression.

Thioredoxin and protein-disulfide isomerase selectivity for redox regulation of proteins in Corynebacterium glutamicum.

Thioredoxins (Trxs) and protein-disulfide isomerases (PDIs) are believed to play a pivotal role in ensuring the proper folding of proteins, facilitating appropriate functioning of proteins, and maintaining intracellular redox homeostasis in bacteria. Two thioredoxins (Trxs) and three thiol-disulfide isomerases (PDIs) have been annotated in Corynebacterium glutamicum. However, nothing is known about their functional diversity in the redox regulation of proteins. Thus, we here analyzed the Trx- and PDI-dependent redox shifts of ribonucleotide reductase (RNR), insulin, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), and several thiol-dependent peroxidases by measuring enzyme activity and thiol status in vitro. We found that the two Trxs and the three PDIs had activities in the cleavage of the disulfidebond, whereas the PDIs had a lower efficiency than the two Trxs. Trx2 could activate thiol-dependent peroxidases with an efficiency comparable with that of Trx1, but the PDIs were inefficient. The redox-active Cys-X-X-Cys motif harbored in both Trxs and PDIs was essential to supply efficiently the donor of reducing equivalents for protein disulfides. In addition, stress-responsive extracytoplasmic function (ECF)-sigma factor H (SigH)-dependent Trxs and PDIs expressions were observed. These results contributed importantly to our overall understanding of reducing functionality of the Trx and PDI systems, and also highlighted the complexity and plasticity of the intracellular redox network.

In vivo assessment of reactive oxygen species production and oxidative stress effects induced by chronic exposure to gamma radiation in Caenorhabditis elegans

In the current study, effects of chronic exposure to ionizing gamma radiation were assessed in the radioresistant nematode Caenorhabditis elegans in order to understand whether antioxidant defences (AODs) could ameliorate radical formation, or if increased ROS levels would cause oxidative damage. This analysis was accompanied by phenotypical as well as molecular investigations, via assessment of reproductive capacity, somatic growth and RNA-seq analysis.The use of a fluorescent reporter strain (sod1::gfp) and two ratiometric biosensors (HyPer and Grx1-roGFP2) demonstrated increased ROS production (H2O2) and activation of AODs (SOD1 and Grx) in vivo. The data showed that at dose-rates ≤10 mGy h-1 defence mechanisms were able to prevent the manifestation of oxidative stress. In contrast, at dose-rates ≥40 mGy h-1 the continuous formation of radicals caused a redox shift, which lead to oxidative stress transcriptomic responses, including changes in mitochondrial functions, protein degradation, lipid metabolism and collagen synthesis. Moreover, genotoxic effects were among the most over-represented functions affected by chronic gamma irradiation, as indicated by differential regulation of genes involved in DNA damage, DNA repair, cell-cycle checkpoints, chromosome segregation and chromatin remodelling. Ultimately, the exposure to gamma radiation caused reprotoxic effects, with >20% reduction in the number of offspring per adult hermaphrodite at dose-rates ≥40 mGy h-1, accompanied by the down-regulation of more than 300 genes related to reproductive system, apoptosis, meiotic functions and gamete development and fertilization.

Cosmic spherules from Widerøefjellet, Sør Rondane Mountains (East Antarctica)

A newly discovered sedimentary accumulation of micrometeorites in the Sør Rondane Mountains of East Antarctica, close to the Widerøefjellet summit at ∼2750 m above sea level, is characterized in this work. The focus here lies on 2099 melted cosmic spherules larger than 200 μm, extracted from 3.2 kg of sampled sediment. Although the Widerøefjellet deposit shares similarities to the micrometeorite traps encountered in the Transantarctic Mountains, both subtle and more distinct differences in the physicochemical properties of the retrieved extraterrestrial particles and sedimentary host deposits are discernable (e.g., types of bedrock, degree of wind exposure, abundance of metal-rich particles). Unlike the Frontier Mountain and Miller Butte sedimentary traps, the size fraction below 240 μm indicates some degree of sorting at Widerøefjellet, potentially through the redistribution by wind, preferential alteration of smaller particles, or processing biases. However, the cosmic spherules larger than 300 μm appear largely unbiased following their size distribution, frequency by textural type, and bulk chemical compositions. Based on the available bedrock exposure ages for the Sør Rondane Mountains, extraterrestrial dust is estimated to have accumulated over a time span of ∼1–3 Ma at Widerøefjellet. Consequently, the Widerøefjellet collection reflects a substantial reservoir to sample the micrometeorite influx over this time interval. Petrographic observations and 3D microscopic CT imaging are combined with chemical and triple-oxygen isotopic analyses of silicate-rich cosmic spherules larger than 325 μm. The major element composition of 49 cosmic spherules confirms their principally chondritic parentage. For 18 glassy, 15 barred olivine, and 11 cryptocrystalline cosmic spherules, trace element concentrations are also reported on. Based on comparison with evaporation experiments reported in literature and accounting for siderophile and chalcophile element losses during high-density phase segregation and ejection, the observed compositional sequence largely reflects progressive heating and evaporation during atmospheric passage accompanied by significant redox shifts, although the influence of (refractory) chondrite mineral constituents and terrestrial alteration cannot be excluded in all cases. Twenty-eight cosmic spherules larger than 325 μm analyzed for triple-oxygen isotope ratios confirm inheritance from mostly carbonaceous chondritic precursor materials (∼55% of the particles). Yet, ∼30% of the measured cosmic spherules and ∼50% of all glassy cosmic spherules are characterized by oxygen isotope ratios above the terrestrial fractionation line, implying genetic links to ordinary chondrites and parent bodies currently unsampled by meteorites. The structural, textural, chemical, and isotopic characteristics of the cosmic spherules from the Sør Rondane Mountains, and particularly the high proportion of Mg-rich glass particles contained therein, imply a well-preserved and representative new sedimentary micrometeorite collection from a previously unstudied region in East Antarctica characterized by distinct geological and exposure histories.

Real-time Imaging of Compartmentalized Oxidant-induced GSH/GSSG Redox Shifts in Undifferentiated Stem Cells

Real-time Imaging of Compartmentalized Oxidant-induced GSH/GSSG Redox Shifts in Undifferentiated Stem Cells

Mathematical modeling of the electrochemical behavior of a polyaniline film for the fast electron transfer kinetic

The electrochemical behavior of a polyaniline (PANI) film as a conductive polymer has been studied using a new proposed mathematical model (PMM). A one-dimensional transient model, considering the doping-dedoping and redox processes for a thin PANI film, was developed based on the cyclic voltammetry method. It was assumed that two reactions occur at the interface of film/electrolyte during the potential sweep: an electrochemical reaction and an adsorption-desorption reaction. The diffusion process of dopant ions was governed by Fick's second law equation. The modeling results were evaluated using the experimental data reported in the literature. The effect of different parameters including bulk concentration of dopants (CA⁎), potential scan rate (v), adsorption rate constant (kad) and desorption rate constant (kde), on the electrochemical behavior of a PANI film were parametrically studied using the PMM. The increase of kad and CA⁎ causes the shift of redox couple to the lower potentials while the increment of kde moves the redox couple to the higher potentials. The increase of parameter v was provides the enhancement of both peak couple currents and the higher peak potential separation.

Selective catalytic reduction of NO by NH3 on cerium modified faujasite zeolite prepared from aluminum scraps and industrial metasilicate

This work was devoted to the study of the selective catalytic reduction of NO by NH3 on calcined and hydrothermal treated cerium loaded zeolite catalysts. The parent faujasite zeolite Na–F (Si/Al = 1.32 and SBET = 749 m2/g) used as support for the preparation of the catalysts was obtained from industrial sodium metasilicate and aluminum scraps. As expected, the NO conversion increases with increasing the percentage of cerium in the structure of the faujasite zeolite. Total NO conversion into N2 is reached at 400 °C at a space velocity of 250 000 h−1. The high conversion is due to the redox shift between Ce3+/Ce4+ and the strong acid sites related to the rare earth present in the framework that is the key in SCR of NO process. Moreover, the highest loaded cerium catalyst retains almost its activity after hydrothermal treatment at 850 °C. This higher loading is desirable for both activity and stability provided that two stages of preparation are used to put the Ce ions in the sodalite cages.

Ceramide: a novel inducer for neural tube defects.

Circulating plasma ceramides, a class of bioactive sphingolipids, are elevated in metabolic disorders, including obesity. Infants of women with these disorders are at 2- to 3-fold greater risk for developing a neural tube defect (NTD). This study aimed to test the effects of embryonic exposure to C2-ceramides (C2) during neural tube closure. Preliminary data shows an increase in NTDs in chick embryos after C2 exposure, and addresses potential mechanisms. Cell and embryo models were used to examine redox shifts after ceramide exposure. While undifferentiated P19 cells were resistant to ceramide exposure, neuronally differentiated P19 cells exhibited an oxidizing shift. Consistent with these observations, GSH E h curves revealed a shift to a more oxidized state in C2 treated embryos without increasing apoptosis or changing Pax3 expression, however cell proliferation was lower. Neural tube defects were observed in 45% of chick embryos exposed to C2, compared to 12% in control embryos. C2 exposure during critical developmental stages increased the frequency of NTDs in the avian model. Increased ROS generation in cell culture, along with the more oxidative GSH E h profiles of C2 exposed cells and embryos, support a model wherein ceramide affects neural tube closure via altered tissue redox environments.

Controls on organic matter accumulation on the early-Cambrian western Yangtze Platform, South China

Abstract The origin of widespread organic-rich shales on the early Cambrian Yangtze Platform of Nanhua Basin (South China) has been attributed to high primary productivity. To test this hypothesis, we generated multiple paleoproductivity (OCAR and PAR), paleoredox (Corg/P ratios), upwelling/restriction (CoEF × MnEF, Co (ppm) × Mn (%), Mo/TOC, and Cd/Mo ratios), and terrigenous flux proxies (Al and unreactive Fe (FeU)) for the lower Cambrian Niutitang Formation in the outer-shelf Jinsha section, which records a typical transition from the organic-rich black shales to overlying organic-lean mudstones or siltstones. These new data were integrated with published paleoredox proxies (iron speciation and redox-sensitive trace metals) for the same section. Our results suggest that the organic-rich (TOC = 4.6 ± 1.8%) lower member (LM; 0–37 m) of the Niutitang Formation records ferruginous conditions, high productivity levels, and low siliciclastic fluxes, and that the organic-poor (TOC = 0.1 ± 0.1%) upper member (UM; 37–329 m) was characterized by dominantly oxic conditions, declining productivity levels, and high siliciclastic fluxes. Our results suggest a redox shift from ferruginous to oxic conditions and enhanced terrigenous fluxes in response to falling sea level from the LM to the UM. Secular variations in primary productivity and redox conditions are strongly correlated, which is consistent with a positive feedback: high primary productivity led to increasing water-column anoxia, which enhanced organic P recycling, stimulating further productivity. Variations in primary productivity may reflect variable upwelling intensity in a semi-restricted shelf setting linked to sea-level changes. Taken together, these findings suggest that a combination of primary productivity, redox conditions, and terrigenous fluxes driven by sea-level changes played a key role in organic matter accumulation on the early-Cambrian western Yangtze Platform.

Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer\u2019s Disease Neurons by Imposed External Cys/CySS Redox Shifts

Redox systems including extracellular cysteine/cystine (Cys/CySS), intracellular glutathione/oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide reduced/oxidized forms (NADH/NAD+) are critical for maintaining redox homeostasis. Aging as a major risk factor for Alzheimer’s disease (AD) is associated with oxidative shifts, decreases in anti-oxidant protection and dysfunction of mitochondria. Here, we examined the flexibility of mitochondrial-specific free NADH in live neurons from non-transgenic (NTg) or triple transgenic AD-like mice (3xTg-AD) of different ages under an imposed extracellular Cys/CySS oxidative or reductive condition. We used phasor fluorescence lifetime imaging microscopy (FLIM) to distinguish free and bound NADH in mitochondria, nuclei and cytoplasm. Under an external oxidative stress, a lower capacity for maintaining mitochondrial free NADH levels was found in old compared to young neurons and a further decline with genetic load. Remarkably, an imposed Cys/CySS reductive state rejuvenated the mitochondrial free NADH levels of old NTg neurons by 71% and old 3xTg-AD neurons by 89% to levels corresponding to the young neurons. Using FLIM as a non-invasive approach, we were able to measure the reversibility of aging subcellular free NADH levels in live neurons. Our results suggest a potential reductive treatment to reverse the loss of free NADH in old and Alzheimer’s neurons.