Neuroprotection conferred by post‐ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation

Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's effect on (i) conferring neuroprotection by measuring infarct volume and neurological deficits 24 h post reperfusion; (ii) cerebral glucose metabolism and lactic acidosis by measuring brain and blood glucose concentrations and protein expression of glucose transporter 1 and 3 (GLUT1, GLUT3), phosphofructokinase (PFK), as well as lactic acidosis by measuring lactate dehydrogenase (LDH), and lactate; and (iii) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation by detecting enzymatic activity and subunit expression at 3 h after reperfusion. When administered upon reperfusion, ethanol (1.5 g/kg) reduced infarct volume by 40% (p < 0.01) and neurological deficits by 48% at 24 h post reperfusion while reducing (p < 0.01) elevations in glycolytic protein expression and lactate levels during early reperfusion (3 h). Ethanol increased the reductions in cerebral glucose concentration at 3 h post reperfusion by 64% (p < 0.01) while enhancing (p < 0.01) post stroke blood glucose concentration, suggesting a reduced cellular glucose uptake and utilization. Ethanol decreased (p < 0.01) stroke‐induced NOX activation by reducing enzymatic activity and gp91^phox expression by 45% and 38%, respectively. Post‐ischemia ethanol treatment exerts neuroprotection through attenuation of hyperglycolysis and associated NOX activation. Because of the lack of associated hypoglycemia and selectivity toward decreasing cerebral metabolism, further investigation of ethanol's use as a post‐stroke therapy, especially in the context of hyperglycemia, seems warranted.     

An evaluation of active acoustic methods for detection of marine mammals in the Canadian Beaufort Sea

A commercially available fisheries sonar was mounted on an icebreaker and evaluated during an environmental baseline study in the Canadian Beaufort Sea, to determine the applicability of active acoustic monitoring (AAM) for marine mammal detection by comparing marine mammal observer (MMO) visual sightings and active acoustic detections. During 170 h of simultaneous MMO and AAM, 115 bowhead whales (Balaena mysticetus) and four beluga whales (Delphinapterus leucas) were visually sighted by MMOs, while 59 sonar detections of bowhead whales occurred using AAM. The fisheries sonar detected 92% of the cetaceans observed within 2,000 m. Additional observations of ringed seals (Pusa hispida) and bearded seals (Erignathus barbatus) were recorded both by MMOs and AAM. Comparative results indicate that a commercially available active acoustic system can consistently detect marine mammals within varying ranges dictated by water column properties. Shallow environments and strong pycnoclines currently present challenges to AAM.     

Nutrient sensing and TOR signaling in yeast and mammals

Coordinating cell growth with nutrient availability is critical for cell survival. The evolutionarily conserved TOR (target of rapamycin) controls cell growth in response to nutrients, in particular amino acids. As a central controller of cell growth, mTOR (mammalian TOR) is implicated in several disorders, including cancer, obesity, and diabetes. Here, we review how nutrient availability is sensed and transduced to TOR in budding yeast and mammals. A better understanding of how nutrient availability is transduced to TOR may allow novel strategies in the treatment for mTOR‐related diseases.     

Temperature and precipitation drive temporal variability in aquatic carbon and GHG concentrations and fluxes in a peatland catchment

The aquatic pathway is increasingly being recognized as an important component of catchment carbon and greenhouse gas (GHG) budgets, particularly in peatland systems due to their large carbon store and strong hydrological connectivity. In this study, we present a complete 5‐year data set of all aquatic carbon and GHG species from an ombrotrophic Scottish peatland. Measured species include particulate and dissolved forms of organic carbon (POC, DOC), dissolved inorganic carbon (DIC), CO₂, CH₄ and N₂O. We show that short‐term variability in concentrations exists across all species and this is strongly linked to discharge. Seasonal cyclicity was only evident in DOC, CO₂ and CH₄ concentration; however, temperature correlated with monthly means in all species except DIC. Although the temperature correlation with monthly DOC and POC concentrations appeared to be related to biological productivity in the terrestrial system, we suggest the temperature correlation with CO₂ and CH₄ was primarily due to in‐stream temperature‐dependent solubility. Interannual variability in total aquatic carbon concentration was strongly correlated with catchment gross primary productivity (GPP) indicating a strong potential terrestrial aquatic linkage. DOC represented the largest aquatic carbon flux term (19.3 ± 4.59 g C m^?2 yr^?1), followed by CO₂ evasion (10.0 g C m^?2 yr^?1). Despite an estimated contribution to the total aquatic carbon flux of between 8 and 48%, evasion estimates had the greatest uncertainty. Interannual variability in total aquatic carbon export was low in comparison with variability in terrestrial biosphere–atmosphere exchange, and could be explained primarily by temperature and precipitation. Our results therefore suggest that climatic change is likely to have a significant impact on annual carbon losses through the aquatic pathway, and as such, aquatic exports are fundamental to the understanding of whole catchment responses to climate change.     

Evidence for climate‐driven synchrony of marine and terrestrial ecosystems in northwest Australia

The effects of climate change are difficult to predict for many marine species because little is known of their response to climate variations in the past. However, long‐term chronologies of growth, a variable that integrates multiple physical and biological factors, are now available for several marine taxa. These allow us to search for climate‐driven synchrony in growth across multiple taxa and ecosystems, identifying the key processes driving biological responses at very large spatial scales. We hypothesized that in northwest (NW) Australia, a region that is predicted to be strongly influenced by climate change, the El Niño Southern Oscillation (ENSO) phenomenon would be an important factor influencing the growth patterns of organisms in both marine and terrestrial environments. To test this idea, we analyzed existing growth chronologies of the marine fish Lutjanus argentimaculatus, the coral Porites spp. and the tree Callitris columellaris and developed a new chronology for another marine fish, Lethrinus nebulosus. Principal components analysis and linear model selection showed evidence of ENSO‐driven synchrony in growth among all four taxa at interannual time scales, the first such result for the Southern Hemisphere. Rainfall, sea surface temperatures, and sea surface salinities, which are linked to the ENSO system, influenced the annual growth of fishes, trees, and corals. All four taxa had negative relationships with the Niño‐4 index (a measure of ENSO status), with positive growth patterns occurring during strong La Niña years. This finding implies that future changes in the strength and frequency of ENSO events are likely to have major consequences for both marine and terrestrial taxa. Strong similarities in the growth patterns of fish and trees offer the possibility of using tree‐ring chronologies, which span longer time periods than those of fish, to aid understanding of both historical and future responses of fish populations to climate variation.     

Vessel noise cuts down communication space for vocalizing fish and marine mammals

Anthropogenic noise across the world's oceans threatens the ability of vocalizing marine species to communicate. Some species vocalize at key life stages or whilst foraging, and disruption to the acoustic habitat at these times could lead to adverse consequences at the population level. To investigate the risk of these impacts, we investigated the effect of vessel noise on the communication space of the Bryde's whale Balaenoptera edeni, an endangered species which vocalizes at low frequencies, and bigeye Pempheris adspersa, a nocturnal fish species which uses contact calls to maintain group cohesion while foraging. By combining long‐term acoustic monitoring data with AIS vessel‐tracking data and acoustic propagation modelling, the impact of vessel noise on their communication space was determined. Routine vessel passages cut down communication space by up to 61.5% for bigeyes and 87.4% for Bryde's whales. This influence of vessel noise on communication space exceeded natural variability for between 3.9 and 18.9% of the monitoring period. Additionally, during the closest point of approach of a large commercial vessel, <10 km from the listening station, the communication space of both species was reduced by a maximum of 99% compared to the ambient soundscape. These results suggest that vessel noise reduces communication space beyond the evolutionary context of these species and may have chronic effects on these populations. To combat this risk, we propose the application or extension of ship speed restrictions in ecologically significant areas, since our results indicate a reduction in sound source levels for vessels transiting at lower speeds.     

The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions

Glutathione is a key cellular antioxidant that is contained in both cytoplasmic and mitochondrial compartments. Previous investigations indicate that depletion of the mitochondrial pool of glutathione can greatly reduce cell viability. In the present investigation, the effect of focal cerebral ischemia on total (reduced plus oxidized) glutathione in mitochondria was assessed using a rat model of middle cerebral artery occlusion. Total glutathione was substantially decreased in mitochondria prepared from severely ischemic focal tissue in both the cerebral cortex and striatum at 2 h of vessel occlusion and persisted for at least the first 3 h of reperfusion. The loss of mitochondrial glutathione was not associated with decreases of the total tissue glutathione content and was not due to the formation of mixed disulfides with mitochondrial proteins. Thus, an imbalance between uptake and release from the mitochondria in the ischemic tissue provides the most likely explanation for the loss. Decreases in glutathione also developed in mitochondria from the moderately ischemic perifocal tissue when the period of arterial occlusion was extended to 3 h. The presence of mitochondrial glutathione depletion during ischemia showed an apparent close association with the subsequent development of tissue infarction. These findings are consistent with a role for the glutathione depletion in determining the susceptibility of brain tissue to focal ischemia.     

Postischemic injury in isolated rat hearts is not aggravated by prior depletion of myocardial glutathione

The aim of this study was to test the hypothesis that a decreased myocardial concentration of reduced glutathione (GSH) during ischemia renders the myocardium more susceptible to injury by reactive oxygen species generated during early reperfusion. To this end, rats were pretreated with L-buthionine-S,R-sulfoximine (2 mmol/kg), which depleted myocardial GSH by 55%. Isolated buffer-perfused hearts were subjected to 30 min of either hypothermic or normothermic no-flow ischemia followed by reperfusion. Prior depletion of myocardial GSH did not lead to oxidative stress during reperfusion, as myocardial concentration of glutathione disulfide (GSSG) was not increased after 5 and 30 min of reperfusion. In addition, prior depletion of GSH did not exacerbate myocardial enzyme release, nor did it impair the recoveries of tissue ATP, coronary flow rate and left ventricular developed pressure during reperfusion after either hypothermic or normothermic ischemia. Even administration of the prooxidant cumene hydroperoxide (20 M) to postischemic GSH-depleted hearts during the first 10 min of reperfusion did not aggravate postischemic injury, although this prooxidant load induced oxidative stress, as indicated by an increased myocardial concentration of GSSG. These results do not support the hypothesis that a reduced myocardial concentration of GSH during ischemia increases the susceptibility to injury mediated by reactive oxygen species generated during reperfusion. Apparently, myocardial tissue possesses a large excess of GSH compared to the quantity of reactive oxygen species generated upon reperfusion. (Mol Cell Biochem 156: 79-85, 1996)     

Postnatal long bone growth in terrestrial placental mammals: Allometry,life history,and organismal traits

The ontogenetic allometry of long bone proportions is poorly understood in Mammalia. It has previously been suggested that during mammalian ontogeny long bone proportions grow more slender (positive allometry; length ∝ circumference^>1.0), although this conclusion was based upon data from a few small‐bodied taxa. It remains unknown how ontogenetic long bone allometry varies across Mammalia in terms of both taxonomy and body size. We collected long bone length and circumference data for ontogenetic samples of 22 species of mammals spanning six major clades and three orders of magnitude in body mass. Using reduced major axis bivariate regressions to compare bone length to circumference, we found that isometry and positive allometry are the most widespread patterns of growth across mammals. Negative allometry (i.e., bones growing more robust during ontogeny) occurs in mammals but is largely restricted to cetartiodactyls. Using regression slope as a proxy for long bone allometry, we compared long bone allometry to life history and organismal traits. Neonatal body mass, adult body mass, and growth rate have a negative relationship with long bone allometry. At an adult mass of roughly 15–20 kg, long bone growth shifts from positive allometry to mainly isometry and negative allometry. There were no significant relationships between ontogenetic long bone allometry and either cursoriality or basal metabolic rate. J. Morphol. © 2012 Wiley Periodicals, Inc.     

Spermatogenesis,sperm cell morphology and accompanying secretions from two interstitial marine mites

The sperm cell morphology and spermatogenesis of Halacaroides antoniazziae Pepato Tiago and da Rocha 2011 and Acaromantis vespucioi Pepato and Tiago 2004 was investigated. Halacaroides sperm cells have a complete acrosomal complex, dense tubules crossing the cytoplasm and modified mitochondria. Mature sperm cells are surrounded by two kinds of secretions. Inside the ejaculatory duct, they lie upon a centre composed of a secretion structured as heaps of elongated bodies. Acaromantis spermatozoa are spindle shaped and lack an acrosomal complex. The plasmalemma is deeply folded; the cytoplasm is very reduced and devoid of organelles. A single kind of globular secretion was found. The sperm mass is surrounded by two layers of amorphous secretions. These species share a peripheral pattern of nuclear condensation during spermatogenesis, a possible apomorphy for most halacarids, and no special adaptation to the interstitial environment could be related to their sperm cell morphology.     

Dental functional traits of mammals resolve productivity in terrestrial ecosystems past and present

We have recently shown that rainfall, one of the main climatic determinants of terrestrial net primary productivity (NPP), can be robustly estimated from mean molar tooth crown height (hypsodonty) of mammalian herbivores. Here, we show that another functional trait of herbivore molar surfaces, longitudinal loph count, can be similarly used to extract reasonable estimates of rainfall but also of temperature, the other main climatic determinant of terrestrial NPP. Together, molar height and the number of longitudinal lophs explain 73 per cent of the global variation in terrestrial NPP today and resolve the main terrestrial biomes in bivariate space. We explain the functional interpretation of the relationships between dental function and climate variables in terms of long- and short-term demands. We also show how the spatially and temporally dense fossil record of terrestrial mammals can be used to investigate the relationship between biodiversity and productivity under changing climates in geological time. The placement of the fossil chronofaunas in biome space suggests that they most probably represent multiple palaeobiomes, at least some of which do not correspond directly to any biomes of today's world.     

Intracellular reduction in ATP levels contributes to CYT997‐induced suppression of metastasis of head and neck squamous carcinoma

The incidence rate of head and neck squamous cell carcinoma (HNSCC) has steadily increased over the past decade. However, treatment options for metastatic HNSCC are often limited and the 5‐year survival rate has remained static. Therefore, the development and assessment of more efficient but less toxic therapeutic strategies is an unmet need for treatment of more extensive HNSCC. Here, we report that CYT997, a novel microtubule‐disrupting agent, exerts strong activity in inhibiting HNSCC cell invasion and metastasis. The loss of invasion capacity by CYT997 was accompanied by an associated increase in cell adhesion and the reversal of epithelial‐mesenchymal transition (EMT). Increased expression of E‐cadherin protein and decreased expression of Vimentin protein became evident in HNSCC cells following CYT997 exposure, which were consistently observed in HNSCC xenografts from the mice receiving CYT997. Moreover, the capacity of invasive HNSCC cells to form pulmonary metastases was significantly blocked with CYT997 treatment, indicating that the diminishment of EMT traits contributes to CYT997‐suppressed metastasis. Intriguingly, CYT997 impaired intracellular ATP levels in HNSCC cells, at least in part, through its inhibitory effect on the mitochondrial protein IF1. The addition of ATP attenuated CYT997‐induced suppression of cell invasion, coupled with down‐regulation of E‐Cadherin and up‐regulation of Vimentin. These findings support a critical role of ATP levels in cell invasion and metastasis under the influence of CYT997. Collectively, our data unveil the mechanism involved in mediating CYT997 action, and provide preclinical rationale for possible clinical application of CYT997 as a novel therapeutic strategy against aggressive HNSCC.     

Density, body mass and parasite species richness of terrestrial mammals

We investigated the relationships between helminth species richness and body mass and density of terrestrial mammals. Cross-species analysis and the phylogenetically independent contrast method produced different results. A non-phylogenetic approach (cross-species comparisons) led to the conclusion that parasite richness is linked to host body size. However, an analysis using phylogenetically independent contrasts showed no relationship between host body size and parasite richness. Conversely, a non-phylogenetic approach generated a negative relationship between parasite richness and host density, whereas the independent contrast method showed the opposite trend – that is, parasite richness is positively correlated with host density. From an evolutionary perspective, our results suggest that opportunities for parasite colonization depend more closely on how many hosts are available in a given area than on how large the hosts are. From an epidemiological point of view, our results confirm theoretical models which assume that host density is linked to the opportunity of a parasite to invade a population of hosts. Our findings also suggest that parasitism may be a cost associated with host density. Finally, we provide some support for the non-linear allometry between density and mammal body mass (Silva and Downing, 1995), and explain why host density and host body mass do not relate equally to parasite species richness.     

Drones and marine mammals in Svalbard,Norway

The impact of remotely piloted aircraft systems (RPAS) on marine mammals remains poorly documented despite their increasing use. In the high-Arctic Archipelago of Svalbard, where marine mammals face increasing pressure from climate change and expanding tourism, the use of RPAS remains largely unregulated. In this study we assessed the impacts of RPAS across a range of species to provide science-based management advice, using a variety of aircraft sizes and approach strategies. We explored RPAS sound levels and animal behavior prior to and after flights. Preexperimental alertness influenced sensitivity to disturbance notably. Harbor seals were more sensitive during prebreeding than during molting, reacting at distances of 80 m, whereas walruses responded at distances <50 m. Polar bears reacted to the sound of RPAS during take-off at 300 m, although response levels were relatively low. White whales reacted to the sight of RPAS when flown ahead of the pod, below 15 m. Variations in sound levels typical in overhead descents and manual flights increased disturbance potential more than RPAS size; preprogrammed flight paths are advised. Our study highlights factors that can influence sensitivity to RPAS including tidal state and swell, the presence of young individuals, ambient noise levels, and RPAS approach strategies.     

Mass spectrometry analysis of human P2X1 receptors; insight into phosphorylation,modelling and conformational changes

Recombinant FlagHis₆ tagged Human P2X1 receptors expressed in HEK293 cells were purified, digested with trypsin and analysed by mass spectroscopy (96% coverage following de‐glycosylation and reduction). The receptor was basally phosphorylated at residues S387, S388 and T389 in the carboxyl terminus, a triple alanine mutant of these residues had a modest ~ 25% increase in current amplitude and recovery from desensitization. Chemical modification showed that intracellular lysine residues close to the transmembrane domains and the membrane stabilization motif are accessible to the aqueous environment. The membrane‐impermeant cross‐linking reagent 3,3′‐Dithiobis (sulfosuccinimidylpropionate) (DTSSP) reduced agonist binding and P2X1 receptor currents by > 90%, and modified lysine residues were identified by mass spectroscopy. Mutation to remove reactive lysine residues around the ATP‐binding pocket had no effect on inhibtion of agonist evoked currents following DTSSP. However, agonist evoked currents were ~ 10‐fold higher than for wild type following DTSSP treatment for mutants K199R, K221R and K199R‐K221R. These mutations remove reactive residues distant from the agonist binding pocket that are close enough to cross‐link adjacent subunits. These results suggest that conformational change in the P2X1 receptor is required for co‐ordination of ATP action.     

Mixotrophy in the terrestrial green alga Apatococcus lobatus (Trebouxiophyceae,Chlorophyta)

The green microalga Apatococcus lobatus is widely distributed in terrestrial habitats throughout many climatic zones. It dominates green biofilms on natural and artificial substrata in temperate latitudes and is regarded as a key genus of obligate terrestrial consortia. Until now, its isolation, cultivation and application as a terrestrial model organism has been hampered by slow growth rates and low growth capacities. A mixotrophic culturing approach clearly enhanced the accumulation of biomass, thereby permitting the future application of A. lobatus in different types of bio‐assays necessary for material and biofilm research. The ability of A. lobatus to grow mixotrophically is assumed as a competitive advantage in terrestrial habitats.     

Vitamin D content in Alaskan Arctic zooplankton,fishes, and marine mammals

We postulated that dietary ingestion of vitamin D may be used by some Alaskan Arctic marine mammal species in addition to, or instead of, cutaneous production to meet nutritional requirements. Zooplankton (n=5) sampled near Kaktovik, Alaska, contained no measurable vitamin D₂ or D₃, but did contain provitamin D (7‐dehydrocholesterol), the cutaneous precursor for previtamin D₃ in mammals. Fillets and livers from five fish species were sampled near Barrow, Alaska, and evaluated for vitamin D₃ content (no vitamin D₂ was detected). Differences in vitamin D₃ content appeared significant (P≤0.10) among fish livers (Kruskal‐Wallis [H test]=8.25, df=4, P=0.08) and among fish fillets (H=7.80, df=4, P=0.01). We also found significant differences in several pairwise comparisons (Mann‐Whitney U‐test) of vitamin D₃ levels in fillets and livers. Blubber from six species of marine mammals had no detectable vitamin D₂. The H test results for blubber vitamin D₃ concentration were highly significant: 28.12, df=5, P<0.001. There were also significant differences in vitamin D₃ content from blubber in pairwise comparisons of primarily invertebrate feeders (bowhead whale (Balaena mysticetus) [mean=4.20 SD±1.10 ng/g], and Pacific walrus (Odobenus rosmarus divergens) [5.43±2.82 ng/g]) vs. primarily piscivorous feeders (ringed seal (Phoca hispida) [746.57±493.00 ng/g] and beluga whale (Delphinapterus leucas) [426.00±174.92 ng/g]) and a semiaquatic terrestrial carnivore (polar bear (Ursus maritimus) [406.17±311.70 ng/g]). The bearded seal (Erignathus barbatus) had intermediate blubber vitamin D₃ concentration (156.83±139.25 ng/g), which may reflect an intermediate‐type feeding strategy or an artifact of the small sample size. Zoo Biol 23:33–43, 2004. © 2004 Wiley‐Liss, Inc.     

Personal model‐assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD

To elucidate the molecular mechanisms underlying non‐alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome‐scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD⁺ and glutathione (GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD⁺ repletion on the development of NAFLD, we added precursors for GSH and NAD⁺ biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof‐of‐concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.     

‘Last In–First Out’: seasonal variations of non‐structural carbohydrates,glucose‐6‐phosphate and ATP in tubers of two Arum species

• Knowledge on the metabolism of polysaccharide reserves in wild species is still scarce. In natural sites we collected tubers of Arum italicum Mill. and A. maculatum L. – two geophytes with different apparent phenological timing, ecology and chorology – during five stages of the annual cycle in order to understand patterns of reserve accumulation and degradation.
• Both the entire tuber and its proximal and distal to shoot portion were utilised. Pools of non‐structural carbohydrates (glucose, sucrose and starch), glucose‐6‐phosphate and ATP were analysed as important markers of carbohydrate metabolism.
• In both species, starch and glucose content of the whole tuber significantly increased from sprouting to the maturation/senescence stages, whereas sucrose showed an opposite trend; ATP and glucose‐6‐phosphate were almost stable and dropped only at the end of the annual cycle. Considering the two different portions of the tuber, both ATP and glucose‐6‐phosphate concentrations were higher in proximity to the shoot in all seasonal stages, except the flowering stage.
• Our findings suggest that seasonal carbon partitioning in the underground organ is driven by phenology and occurs independently of seasonal climate conditions. Moreover, our results show that starch degradation, sustained by elevated ATP and glucose‐6‐phosphate pools, starts in the peripheral, proximal‐to‐shoot portion of the tuber, consuming starch accumulated in the previous season, as a ‘Last In–First Out’ mechanism of carbohydrate storage.

     

Effects of aurothioglucose and dietary se on glutathione S-Transferase activities and glutathione concentrations in chick tissues

Experiments were conducted to determine whether the increased glutathione S-transferase (GSH-T) activity associated with selenium (Se) deficiency is necessarily related to losses in the activity of Se-dependent glutathione peroxidase (SeGSHpx) in chicks. Nutritional Se status was altered in two ways: by treatment with an antagonist of Se utilization, aurothioglucose (AuTG), and by feeding diets containing excess Se. Chicks given AuTG (10–30 mg AU/kg, sc) had growth rates and hepatic GSH concentrations that were comparable to those of saline-treated controls; however, their plasma GSH levels exceeded those of either Se-deficient (6-fold) or-adequate (3-fold) saline-treated chicks. Hepatic SeGSHpx activities of AuTG-treated chicks were hals those of controls under conditions of Se-adequacy; however, this effect was not detected when Se was deficient. Hepatic GSH-T_CDNB (assayed with 1-chloro-2,4-dinitrobenzene) activities of AuTG-treated chicks were significantly greater than those of controls when Se was deficient (i.e., when SeGSHpx activity was 12% of the Se-adequate level); however, deprivation of Se did not affect GSH-T_CDNB activity in the absence of AuTG. chicks fed excess Se (6–20 ppm as Na₂SeO₃) in diets containing either low (2 IU/kg) or adequate (100 IU/kg) VE, showed hepatic GSH-T_CDNB activities and GSH concentrations greater than those of Se-adequate (0.2 ppm Se) chicks by 100% and 40%, respectively. That increased hepatic GSH-T_CDNB activity can occur because of either AuTG or excess Se status under conditions wherein SeGSHpx activity is not affected indicates that the transferase response is not directly related to changes in the peroxidase.