Low Metabolic Rate Research Articles

In vitro investigations on the hepatotoxicity and genotoxicity of food‐relevant pyrrolizidine alkaloids

Pyrrolizidine alkaloids (PA) are secondary plant metabolites occurring in a great many plant species worldwide, known to exhibit hepatotoxic, genotoxic and carcinogenic properties after metabolic activation. In recent years, contamination of food, feed and herbal medicines with PA has become an increasing problem. The concept of interim relative potency factors (iREP) proposed by Merz and Schrenk in 2016 was a new approach for risk assessment of PA. While existing approaches of risk assessment assumed equivalent toxic potency for all PA congeners, the approach of Merz and Schrenk considered the structural features of individual PA congeners based on existing data from the literature. In order to generate further data on the structure‐specific toxicity of PA, congeners of different structural classes were investigated in different in vitro test systems.In vitro cytotoxicity was investigated in primary rat hepatocytes, HepG2 C9 cells (overespressing human CYP3A4) and naïve HepG2 cells. Overall, it could be observed that lasiocarpine and the cyclic di‐esters (except monocrotaline) showed much stronger cytotoxic effects in comparison to the tested mono‐esters in both, primary rat hepatocytes and in HepG2 C9 cells. Primary hepatocytes were the most sensitive cells investigating cytotoxicity of different PA congeners, followed by the HepG2 C9 cells. This is confirmed by markedly higher metabolism rates for all investigated PA in primary rat hepatocytes determined in the metabolism experiments. In naïve HepG2 cells no cytotoxic effects could be observed. The influence of cytochrome P450 (CYP) on the formation of toxic metabolites seem to play a crucial role. This assumption could be beared using ketoconazole as CYP inhibitor and testing various pre‐incubation times in primary rat hepatocytes. CYP activity was measured using 7‐ Benzoxyresorufin‐O‐Dealkylase (BROD) assay in primary rat hepatocytes and in HepG2 C9 cells. Glutahione (GSH) depletion using buthionine sulfoximine (BSO) showed slight stronger cytotoxic effects for several PA, but not for all tested.In contrast to the negative results of mutagenicity in ames fluctuation assay using Salmonella strains TA98 and TA100 with and without metabolic activation by S9 mix, all tested PA congeners showed micronuclei induction in the HepG2 C9 cell line. Again, laisocarpine and the cyclic di‐esters (except monocrotaline) were the most potent ones. In conclusion, the data from cytotoxicity and genototoxicity experiments from the tested PA congeners confirm published iREP factors with a few exceptions, in particular for monocrotaline or echimidine. Additionally, metabolism of six selected PA was studied in primary rat hepatocytes and HepG2 C9 cells. Genrally, it was found that almost all tested cyclic and open‐chained di‐esters (except retrorsine) showed much higher metabolism rates in both cell types, in comparison to the mono‐esters, for which only low metabolism rates could be measured. The same was observed for the quantified amounts of reactive metabolites in the supernatants of both cell types. In general, also these data bear the results from cytotoxicity and genotoxicity experiments and help to better understand the complex metabolism and the structure‐specific toxicity of different PA congeners.

0484 The association between obstructive sleep apnea, energy balance and body composition: a clinical cohort

Abstract Introduction A couple of studies investigated the energy balance in patients with obstructive sleep apnea (OSA) but the results were inconclusive. Moreover, OSA have been associated with visceral adiposity but the mechanism has not been fully elucidated. We hypothesized that OSA was associated with lower basal metabolic rate (BMR) and increased nutrition intake which further attributed to body adiposity. The aim of the present study is to determine the association between OSA, and BMR, nutrition intake, and body composition (BC). Methods Patients were recruited from referrals to sleep lab for suspect OSA. Measurement of the BMR with indirect calorimetry and BC with bioelectrical impedance analysis, and blood sampling were conducted in the morning next to the overnight polysomnography. Afterward, participants were evaluated with short -form IPAQ, 3-day intake dietary, 7-day sleep log, and wore Actiwatch for 7 days. The outcomes are resting energy expenditure (REE) and respiratory quotien (RQ), total fat mass (TFM), fat free mass (FFM), nutrition intake, daily total activity count, nightly sleep hour, and hormone. The association between OSA □apnea hypopnea index (AHI) >=15/h□ and REE, RQ, TFM, and FFM was analyzed with multivariable linear regression. Results 85 patients were enrolled with median age 41.7 y/o, 78.6% male, body mass index (BMI) 25.4 kg/m2, and AHI 28.8/h. Compared to no OSA, patients with OSA had higher BMI, RQ, TFM, activity count, and similar age, gender, REE, FFM, nutrition intake, sleep hour, cortisol, leptin, and Ghrelin. OSA was independently associated with RQ (coefficient 0.031; 95% CI 0.004-0.057, p=0.022) with adjustment of age, gender, BMI, and activity count but not associated with REE, TFM, and FFM. Conclusion Though OSA may be associated with metabolic dysregulation, it was not associated with energy balance and BC. Further validation of the findings in a large scale and multi-ethnicity cohort to validate the findings of the present study is warranted. Support (if any) National Science and Technology Council, Taiwan (NST 111-2314-B-002-293; MOST 109-2314-B-002-252); Ministry of Education (NTU-107L900502, 108L900502, 109L900502)”, National Taiwan University Hospital (NTHU 108-S4331, 109-42, 111-S0298, 111-X0033); MediaTek Inc. (201802034 RIPD), and LARGAN Health AI-Tec CO., Ltd (202003021 RIPB)

Respiratory plasticity during acclimation to hypoxia and following a recovery in normoxia

Phenotypic plasticity manifested after acclimatization is a very important source of biological variability among fish species. We hypothesized that hypoxic acclimation, besides potentially generating a temporary hypoxic respiratory phenotype, would also manifest as a continued benefit after reacclimation to normoxia. Hence, we holistically characterized the respiratory phenotype of European sea bass ( Dicentrarchus labrax (Linnaeus, 1758)) acclimated to normoxia with or without prior acclimation to hypoxia. Compared with the original normoxic phenotype, prior acclimation to hypoxia and return to normoxia produced a 27% higher absolute aerobic scope (AAS), a 24% higher citrate synthase activity in red muscle, and a 28% lower excess post exercise O2 consumption. Additional testing of hypoxia-acclimated fish under normoxia explored the specific effects of hypoxic acclimation. The hypoxic phenotype, when compared with the original normoxic phenotype, had a lower standard metabolic rate, a better hypoxia performance, and a lower minimum PO2 for supporting 50% AAS. Thus, respiratory plasticity allows sea bass to improve its maximum aerobic capacity after returning to normoxia from hypoxic acclimation, a potential benefit from exploiting a hypoxic habitat. Given this respiratory malleability, general predictions for marine fish exploiting a more hypoxic future should better consider respiratory plasticity and prolonged effects of hypoxic exposures.

Correlated responses to selection for different cell size in Chlamydomonas reinhardtii using divergent evolutionary pathways

AbstractCell size is an important trait that is often correlated with organisms’ survival under different thermal environments, and in the case of phytoplankton, it is also related to survival under different light irradiance. While smaller phytoplankton thrive under warm and high light (summer conditions), larger cells seem to be more efficient under cool and low light conditions (winter conditions). In this study, we used different evolutionary pathways, nitrogen depletion and size selection, to select for differences in average cell diameter in the single-celled alga Chlamydomonas reinhardtii. We tested whether there was a size-related fitness (growth rate) advantage across two light intensities and two temperatures; environmental effects that have dramatic effects on algal growth. Under these environmental conditions we then tested how the evolutionary pathway to reduced cell size affected fitness and photophysiology. The results suggest that the relationship between size and growth rate in C. reinhardtii is strongly correlated with changes in the photosynthetic apparatus in different sized cells. Large-selected cells evolved to have smaller light-harvesting antennae, making them less susceptible to photodamage. However, they accumulate larger amounts of reactive oxygen species, potentially due to their lack of antioxidant carotenoids. In addition, the maximum growth rate was reduced, potentially due to their reduced ability to repair PSII due to lower metabolic rates. Similar responses were observed in lines that evolved to have smaller cells under nitrogen depletion. The results demonstrate that different evolutionary pathways to reduced cell size result in different changes in metabolism, with N-depleted and Small-selected cell lineages having similar sizes, but thriving differently under winter/summer conditions. With large production systems in mind, it is possible to assume that the choice of strains selected using adaptative laboratory evolution or direct selection on size can affect the overall production yield and carbon capture according to the seasons and possibly other abiotic parameters.

Constant temperature and fluctuating temperature have distinct effects on hypoxia tolerance in killifish (Fundulus heteroclitus).

Climate change is leading to rapid change in aquatic environments, increasing the mean and variability of temperatures, and increasing the incidence of hypoxia. We investigated how acclimation to constant temperatures or to diel temperature fluctuations affects hypoxia tolerance in mummichog killifish (Fundulus heteroclitus). Killifish were acclimated to constant cool (15°C), constant warm (25°C) or a diel temperature cycle (15°C at night, 25°C during day) for 6 weeks. We then measured hypoxia tolerance (time to loss of equilibrium in severe hypoxia, tLOE; critical O2 tension, Pcrit), whole-animal metabolism, gill morphology, haematology and tissue metabolites at 15°C and 25°C in a full factorial design. Among constant temperature groups, tLOE was highest and Pcrit was lowest in fish tested at their acclimation temperature. Warm-acclimated fish had lower metabolic rate at 25°C and greater gill surface area (less coverage of lamellae by interlamellar cell mass, ILCM), but cool-acclimated fish had greater brain glycogen stores. Therefore, effects of constant temperature acclimation on hypoxia tolerance were temperature specific and not exhibited broadly across test temperatures, and they were associated with different underlying mechanisms. Hypoxia tolerance was less sensitive to test temperature in fish acclimated to fluctuating temperatures compared with fish acclimated to constant temperature. Acclimation to fluctuating temperatures also increased haemoglobin-O2 affinity of the blood (decreased P50) compared with constant temperature groups. Therefore, acclimation to fluctuating temperatures helps maintain hypoxia tolerance across a broader range of temperatures, and leads to some distinct physiological adjustments that are not exhibited by fish acclimated to constant temperatures.

Relative influence of individual characteristics on critical WBGT limits in young adults (PSU HEAT Project)

Critical environmental limits are temperature-humidity thresholds above which heat balance cannot be maintained for a given metabolic heat production. This study examined the association between individual characteristics [sex, body surface area (A D ), aerobic capacity (V̇O 2max ; L∙min-1), and body mass (m b )] and critical environmental limits in young adults. Forty-four (20 M/24 F; 23±4 yr) subjects were exposed to progressive heat stress in an environmental chamber at two low net metabolic rates (M net ); minimal activity (MinAct; M net = 160±35 W) and light ambulation (LightAmb; M net = 259±54 W). In 2 hot-dry (HD; <25% rh) environments, ambient water vapor pressure (P a = 12 or 16 mmHg) was held constant and dry-bulb temperature (T db ) was systematically increased. In 2 warm-humid (WH; >50% rh) environments, T db was held constant at 34 or 36 °C and P a was systematically increased. The critical wet-bulb globe temperature (WBGT crit ) was determined for each condition. There were no sex differences in WBGT crit for any condition ( p ≥ 0.21). During MinAct, only m b was retained in a backward linear regression model explaining the variance in WBGT crit in WH (R 2adj = 0.08, p < 0.001), whereas m b and V̇O 2max were retained for HD environments (R 2adj = 0.09, p < 0.001). During LightAmb, m b and A D were retained in the model for both WH (R 2adj = 0.46, p < 0.001) and HD environments (R 2adj = 0.22; p < 0.001). These data demonstrate the relative importance of individual characteristics on WBGTcrit during low-intensity weight-bearing (LightAmb) and non-weight-bearing (MinAct) activity in extreme thermal environments. This work was supported by NIH R01 AG067471. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ammonoid extinction versus nautiloid survival: Is metabolism responsible?

Abstract Understanding the mechanism of selective extinction is important in predicting the impact of anthropogenic environmental changes on current ecosystems. The selective extinction of externally shelled cephalopods at the Cretaceous-Paleogene (K-Pg) mass extinction event (ammonoids versus nautiloids) is often studied, but its mechanism is still debated. We investigate the differences in metabolic rate between these two groups to further explore the causes of selective extinction. We use a novel metabolic proxy—the fraction of metabolic carbon in the stable carbon isotope ratio of shell material (Cmeta)—to determine metabolic rate. Using this approach, we document significant differences in Cmeta among modern cephalopod taxa (Nautilus spp., Argonauta argo, Dosidicus gigas, Sepia officinalis, and Spirula spirula). Our results are consistent with estimates based on oxygen consumption, suggesting that this proxy is a reliable indicator of metabolic rate. We then use this approach to determine the metabolic rates of ammonoids and nautiloids that lived at the end of the Cretaceous (Maastrichtian). Our results show that the nautiloid Eutrephoceras, which survived the K-Pg mass extinction event, possessed a lower metabolic rate than co-occurring ammonoids (Baculites, Eubaculites, Discoscaphites, and Hoploscaphites). We conclude that the lower metabolic rate in nautiloids was an advantage during a time of environmental deterioration (surface-water acidification and resulting decrease in plankton) following the Chicxulub asteroid impact.

The impact of selected abiotic factors on Artemia hatching process through real-time observation of oxygen changes in a microfluidic platform

Current studies on abiotic impacts on Artemia, a crustacean which is widely used in aquaculture, and ecotoxicology, often focus on endpoint analysis (e.g., hatching rates, survival). Here, we demonstrate that a mechanistic understanding can be obtained through measurement of oxygen consumption in real-time over an extended time period in a microfluidic platform. The platform enables high level control of the microenvironment and direct observation of morphological changes. As a demonstration, temperature and salinity are chosen to represent critical abiotic parameters that are also threatened by climate change. The hatching process of Artemia consists of four different stages: hydration, differentiation, emergence, and hatching. Different temperatures (20, 35, and 30 °C) and salinities (0, 25, 50, and 75 ppt) are shown to significantly alter the duration of hatching stages, metabolic rates, and hatchability. Specifically, the metabolic resumption of dormant Artemia cysts was significantly enhanced at higher temperatures and moderate salinity, however, the time needed for this resumption was only dependent on higher temperatures. Hatchability was inversely related to the duration of the differentiation stage of hatching, which persisted longer at lower temperatures and salinities. The current approach of investigation of metabolism and corresponding physical changes can be employed to study hatching processes of other aquatic species, even those with low metabolic rate.

Life-History Traits and Acclimation Ability of a Copepod Species from the Dripping Waters of the Corchia Cave (Apuan Alps, Tuscany, Italy)

Copepods are the dominant crustacean group in groundwater, where they perform valuable ecosystem services related to carbon recycling. The life-history traits of stygobitic (groundwater-obligate dweller) copepods, however, have only been casually studied in the past. In addition, next to nothing is known about the responses of stygobitic copepods to climate change. In this study, we investigated the life-history traits and respiratory metabolism of a species of harpacticoid copepods, Moraria sp., endemic to the Corchia Cave in the Apuan Alps (Italy). We collected the specimens of Moraria sp. from the dripping waters of the cave and observed their development, survival, and reproduction rates in the laboratory for one year. We also evaluated the acclimation ability of adult females of Moraria sp. by measuring their oxygen consumption in a temperature range from 8 °C (average annual temperature of the dripping water in the Stalactites Gallery of the Corchia Cave) to 12.5 °C (maximum temperature of the dripping water of the cave expected according to climate change scenarios in 2100). Our results indicate that Moraria sp. Is a stenothermal species showing remarkable stygobitic traits (long life span, low metabolic rates). We noted that the metabolism of this species is significantly affected by small (+1.5 °C) thermal changes. Our results showed no metabolic compensation occurring in this species over two weeks of exposure to temperatures higher than 8 °C. The outcomes of this study suggest that Moraria sp. May not be able to tolerate thermal changes brought on by climate change.

From metabolism to behaviour – Multilevel effects of environmental methamphetamine concentrations on fish

Methamphetamine (METH) is a concerning drug of abuse that produces strong psychostimulant effects. The use of this substance, along with the insufficient removal in the sewage treatment plants, leads to its occurrence in the environment at low concentrations. In this study, brown trout (Salmo trutta fario) were exposed to 1 μg/L of METH as environmental relevant concentration for 28 days in order to elucidate the complex effects resulting from the drug, including behaviour, energetics, brain and gonad histology, brain metabolomics, and their relations. Trout exposed to METH displayed lowered activity as well as metabolic rate (MR), an altered morphology of brain and gonads as well as changes in brain metabolome when compared to controls. Increased activity and MR were correlated to an increased incidence of histopathology in gonads (females - vascular fluid and gonad staging; males - apoptotic spermatozoa and peritubular cells) in exposed trout compared to controls. Higher amounts of melatonin in brain were detected in exposed fish compared to controls. Tyrosine hydroxylase expression in locus coeruleus was related to the MR in exposed fish, but not in the control. Brain metabolomics indicated significant differences in 115 brain signals between control and METH exposed individuals, described by the coordinates within the principal component analyses (PCA) axes. These coordinates were subsequently used as indicators of a direct link between brain metabolomics, physiology, and behaviour - as activity and MR varied according to their values. Exposed fish showed an increased MR correlated with the metabolite position in PC1 axes, whereas the control had proportionately lower MR and PC1 coordinates. Our findings emphasize the possible complex disturbances in aquatic fauna on multiple interconnected levels (metabolism, physiology, behaviour) as a result of the presence of METH in aquatic environments. Thus, these outcomes can be useful in the development of AOP's (Adverse Outcome Pathways).

Effects of substrate roughening on the swimming performance of Schizothorax wangchiachii (Fang, 1936) in the Heishui River: Implications for vertical slot fishway design.

Re-establishing the natural connectivity of rivers using fishways may mitigate the unfavourable effects of dam construction on riverine biodiversity and freshwater fish populations. Knowledge of the swimming performance of target species in specific regions is critical for designing fishways with a high passage efficiency. Substrate roughening with river stones of fishways is considered to improve fish swimming capacity by benefiting from reduced-velocity zones with lower energetic costs. However, the effectiveness of rough substrates in energy metabolism is rarely tested. We investigated the effect of substrate roughening on the swimming capacity, oxygen consumption and behaviour of Schizothorax wangchiachii from the Heishui River in a flume-type swimming respirometer. The results showed that substrate roughening improved critical and burst swimming speed by ~12.9% and ~15.0%, respectively, compared to the smooth substrate. Our results demonstrate that increased reduced-velocity zones, lowered metabolic rate and tail-beat frequency support our hypothesis that lower energetic costs improve fish swimming performance in rough substrate compared to smooth treatment. The traversable flow velocity model predicted that maximum traversable flow velocity and maximum ascent distance were higher over rough compared to smooth substrate fishways. Fishway substrate roughening may be a practical approach to improve fish swimming upstream for demersal riverine fish.

Microbial diversity and metabolic function in duodenum, jejunum and ileum of emu (Dromaius novaehollandiae)

Emus (Dromaius novaehollandiae), a large flightless omnivorous ratite, are farmed for their fat and meat. Emu fat can be rendered into oil for therapeutic and cosmetic use. They are capable of gaining a significant portion of its daily energy requirement from the digestion of plant fibre. Despite of its large body size and low metabolic rate, emus have a relatively simple gastroinstetinal (GI) tract with a short mean digesta retention time. However, little is known about the GI microbial diversity of emus. The objective of this study was to characterize the intraluminal intestinal bacterial community in the different segments of small intestine (duodenum, jejunum, and ileum) using pyrotag sequencing and compare that with the ceca. Gut content samples were collected from each of four adult emus (2 males, 2 females; 5–6 years old) that were free ranged but supplemented with a barley-alfalfa-canola based diet. We amplified the V3-V5 region of 16S rRNA gene to identify the bacterial community using Roche 454 Junior system. After quality trimming, a total of 165,585 sequence reads were obtained from different segments of the small intestine (SI). A total of 701 operational taxonomic units (OTUs) were identified in the different segments of small intestine. Firmicutes (14–99%) and Proteobacteria (0.5–76%) were the most predominant bacterial phyla in the small intestine. Based on species richness estimation (Chao1 index), the average number of estimated OTUs in the small intestinal compartments were 148 in Duodenum, 167 in Jejunum, and 85 in Ileum, respectively. Low number of core OTUs identified in each compartment of small intestine across individual birds (Duodenum: 13 OTUs, Jejunum: 2 OTUs, Ileum: 14 OTUs) indicated unique bacterial community in each bird. Moreover, only 2 OTUs (Escherichia and Sinobacteraceae) were identified as core bacteria along the whole small intestine. PICRUSt analysis has indicated that the detoxification of plant material and environmental chemicals seem to be performed by SI microbiota, especially those in the jejunum. The emu cecal microbiome has more genes than SI segments involving in protective or immune response to enteric pathogens. Microbial digestion and fermentation is mostly in the jejunum and ceca. This is the first study to characterize the microbiota of different compartments of the emu intestines via gut samples and not fecal samples. Results from this study allow us to further investigate the influence of the seasonal and physiological changes of intestinal microbiota on the nutrition of emus and indirectly influence the fatty acid composition of emu fat.

Brain BOLD and NIRS response to hyperoxic challenge in sickle cell disease and chronic anemias

PurposeCongenital anemias, including sickle cell anemia and thalassemia, are associated with cerebral tissue hypoxia and heightened stroke risks. Recent works in sickle cell disease mouse models have suggested that hyperoxia respiratory challenges can identify regions of the brain having chronic tissue hypoxia. Therefore, this work investigated differences in hyperoxic response and regional cerebral oxygenation between anemic and healthy subjects. MethodsA cohort of 38 sickle cell disease subjects (age 22 ± 8 years, female 39%), 25 non-sickle anemic subjects (age 25 ± 11 years, female 52%), and 31 healthy controls (age 25 ± 10 years, female 68%) were examined. A hyperoxic gas challenge was performed with concurrent acquisition of blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS). In addition to hyperoxia-induced changes in BOLD and NIRS, global measurements of cerebral blood flow, oxygen delivery, and cerebral metabolic rate of oxygen were obtained and compared between the three groups. ResultsRegional BOLD changes were not able to identify brain regions of flow limitation in chronically anemic patients. Higher blood oxygen content and tissue oxygenation were observed during hyperoxia gas challenge. Both control and anemic groups demonstrated lower blood flow, oxygen delivery, and metabolic rate compared to baseline, but the oxygen metabolism in anemic subjects were abnormally low during hyperoxic exposure. ConclusionThese results indicated that hyperoxic respiratory challenge could not be used to identify chronically ischemic brain. Furthermore, the low hyperoxia-induced metabolic rate suggested potential negative effects of prolonged oxygen therapy and required further studies to evaluate the risk for hyperoxia-induced oxygen toxicity and cerebral dysfunction.

Genome Analysis of Pseudomonas aeruginosa Strains from Chronically Infected Patients with High Levels of Persister Formation

The appearance of persister cells with low metabolic rates are key factors leading to antibiotic treatment failure. Such persisters are multidrug tolerant and play a key role in the recalcitrance of biofilm-based chronic infections. Here, we present the genomic analyses of three distinct Pseudomonas aeruginosa Egyptian persister-isolates recovered from chronic human infections. To calculate the persister frequencies, viable counts were determined before and after treatment with levofloxacin. The susceptibilities of isolates to different antibiotics were determined using the agar-dilution method. To determine their recalcitrance, the levofloxacin persisters were further challenged with lethal concentrations of meropenem, tobramycin, or colistin. Furthermore, the biofilm formation of the persister strains was estimated phenotypically, and they were reported to be strong biofilm-forming strains. The genotypic characterization of the persisters was performed using whole genome sequencing (WGS) followed by phylogenetic analysis and resistome profiling. Interestingly, out of the thirty-eight clinical isolates, three isolates (8%) demonstrated a persister phenotype. The three levofloxacin-persister isolates were tested for their susceptibility to selected antibiotics; all of the tested isolates were multidrug resistant (MDR). Additionally, the P. aeruginosa persisters were capable of surviving over 24 h and were not eradicated after exposure to 100X-MIC of levofloxacin. WGS for the three persisters revealed a smaller genome size compared to PAO1-genome. Resistome profiling indicated the presence of a broad collection of antibiotic-resistance genes, including genes encoding for antibiotic-modifying enzymes and efflux pump. Phylogenetic analysis indicated that the persister isolates belong to a distinct clade rather than the deposited P. aeruginosa strains in the GenBank. Conclusively, the persister isolates in our study are MDR and form a highly strong biofilm. WGS revealed a smaller genome that belongs to a distinct clade.

Short-Term Moderate Energy Restriction Does Not Affect Indicators of Oxidative Stress and Genotoxicity in Humans

Restriction of energy intake (ER), without malnutrition of essential nutrients, has repeatedly been demonstrated to increase longevity in rodents. In the antioxidant theory of aging the lack of balance between the generation of free radicals and free radical scavenging was thought to be a main causal agent in the aging process. From this point of view the antiaging effect induced by ER might be due to the lower rate of free-radical production and related damage induced by a lower metabolic rate. The antiaging effects of ER might also occur in humans. This study explored the effects of a 10-week moderately energy-restricted diet (80% of habitual) in 24 non-obese middle-aged men (16 ER subjects, 8 controls) on resting metabolic rate (RMR) and indicators of the primary antioxidant defense system, oxidative stress and genotoxicity. RMR decreased significantly in both groups, even when adjustments were made for the change in body composition. The increase in blood vitamin C concentrations correlated with the increase in urinary 8-hydroxy-deoxyguanosine (80HdG) excretion. The change in urinary 80HdG excretion also correlated with the change in RMR per kg fat-free mass. No differences between groups were found for changes in indicators of genotoxicity, erythrocyte catalase, glutathione peroxidase and superoxide dismutase activity and in plasma vitamin E, A or β-carotene concentrations. We conclude that 10 weeks of moderate ER did not affect indicators of antioxidative capacity, oxidative stress and genotoxicity of humans. Since subjects were not in energy balance at the end of the study, no conclusions can be made with respect to long-term effects.

Gas exchange patterns for a small, stored-grain insect pest, Tribolium castaneum.

Insects breathe using one or a combination of three gas exchange patterns; continuous, cyclic and discontinuous, which vary in their rates of exchange of oxygen, carbon dioxide and water. In general, there is a trade-off between lowering gas exchange using discontinuous exchange that limits water loss at the cost of lower metabolic rate. These patterns and hypotheses for the evolution of discontinuous exchange have been examined for relatively large insects (>20 mg) over relatively short periods (<4 h), but smaller insects and longer time periods have yet to be examined. We measured gas exchange patterns and metabolic rates for adults of a small insect pest of grain, the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), using flow-through respirometry in dry air for 48 h. All adults survived the desiccating measurement period; initially they used continuous gas exchange, then after 24 h switched to cyclic gas exchange with a 27% decrease in metabolic rate, and then after 48 h switched to discontinuous gas exchange with increased interburst duration and further decrease in metabolic rate. The successful use of the Qubit, a lower cost and so more common gas analyser, to measure respiration in the very small T. castaneum, may prompt more flow-through respirometry studies of small insects. Running such studies over long durations may help to better understand the evolution of respiration physiology and thus suggest new methods of pest management.

Development and validation of a predictive nomogram for sarcopenia among older people in China.

Development and validation of a predictive nomogram for sarcopenia among older people in China.

Metabolic turnover rate, digestive enzyme activities, and bacterial communities in the white shrimp Litopenaeus vannamei under compensatory growth.

The present work aimed to evaluate the effects promoted by a phase of compensatory growth on metabolic turnover rate, digestive enzyme activity, and bacterial biota of the Pacific white shrimp Litopenaeus vannamei kept under different feeding regimes. Three treatments were evaluated as follows: 70% feed restriction during 3 (T3) and 6 (T6) days, followed by a period of feeding to satiety, and a control treatment without restriction periods. The results showed a full compensatory growth in treatments T3 and T6 by day 35 of the bioassay. A significant increase in trypsin and lipase (T6) activities was observed during compensatory growth, whereas specific amylase activity was significantly lower in treatment T6 compared to T3 but not significantly different from the control group. To determine the metabolic turnover rate of nitrogen in muscle tissue, an analysis of nitrogen isotope values (δ15N) at natural abundance levels was performed. At the end of the experimental period, shrimp under feed restriction had lower metabolic turnover rates and longer nitrogen residence times (t 50) in muscle tissue, as compared to individuals in the control treatment. Regarding the changes in the bacterial communities in shrimp gut, no significant differences were observed at the phylum level, with Proteobacteria being the most abundant bacteria, followed by Actinobacteria. At family taxa level, Rhodobacteraceae presented the highest relative abundance in all treatments, whereas a decrease in Vibrionaceae was observed in treatments T3 and T6 when compared to control shrimps during compensatory growth. At the genus level, a decrease in Celeribacter, Catenococcus, and Epibacterium, and an increase in Ruegeria and Shimia, were identified in shrimp subjected to feed restriction when compared to control organisms during compensatory growth (day 14). At the end of the experimental period, the evaluated parameters showed similar results as those observed in the control treatment, suggesting a normalization of the metabolism and the physiological state. The present findings contribute to a better understanding on the physiological effects produced during compensatory growth in shrimp, which in turn could assist in the development of improved feeding strategies in benefit of the aquaculture industry.

Phenotypic specialization of the pea aphid in its southern limit of distribution

The success of biological invasions ultimately relies on phenotypic traits of the invasive species. Aphids, which include many important pests worldwide, may have been successful invading new environments partly because they can maximize reproductive output by becoming parthenogenetic and losing the sexual phase of their reproductive cycle. However, invasive populations of aphids invading wide ranges can face contrasting environmental conditions and requiring different phenotypic strategies. Besides transitions in their reproductive cycle, it is only partially known which phenotypic traits might be associated to the invasion success of aphid populations in extended novel ranges. Here, we used four genotypes of the pea aphid Acyrthosiphon pisum from two localities in Chile to test for phenotypic specialization that might explain their establishment and spread in habitats exhibiting contrasting environmental conditions. We show that lineages living at a higher latitude with low temperatures show, in addition to facultative sexual reproduction, smaller body sizes, lower metabolic rates and a higher tolerance to the cold than the obligate asexual lineages living in a mild weather, at the expense of fecundity. Conversely, at higher temperatures only asexual lineages were found, which exhibit larger body sizes, higher reproductive outputs and consequently enhanced demographic ability. As a result, in conjunction with the reproductive mode, lineage specialization in physiological and life-history traits could be taken into account as an important strategy for populations of pea aphid to effectively invade extended novel ranges comprising different climatic conditions.

The Association between Low CO2 Production and Central Sleep Apnea in Men with Heart Failure.

Rationale: Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) is prevalent in some patients with heart failure with reduced ejection fraction (HFrEF). Theoretical models of Hunter-Cheyne-Stokes breathing predict that a low metabolic rate (MR) predisposes one to CSA. Objectives: In this study, we examined the role of MR in the pathogenesis of CSA. Methods: A physiological study was conducted in a sleep laboratory at a U.S. Department of Veterans Affairs medical center. Patients were 28 consecutive male Veterans with stable HFrEF. After an adaptation night, polysomnography, left ventricular ejection fraction, pulmonary function tests, carbon dioxide production ([Formula: see text]), and arterial blood samples were obtained under strict standardized conditions. Physiological variables were then entered into regression models to examine the association with CSA. Results: Body mass index varied from 20 to 40 kg/m2, and [Formula: see text] ranged from 167 to 434 ml/min. In the final regression model, low [Formula: see text] and low body mass index were associated with CSA index. [Formula: see text] had the strongest association (95% confidence interval, -0.36 to -0.06; P = 0.007). Conclusions: In patients with HFrEF, a low MR and related low [Formula: see text], but not low oxygen consumption, were associated with CSA. Mechanistically, in the face of low MR and [Formula: see text], a given change in ventilation results in large swings in partial pressure of CO2, thus promoting CSA. To our knowledge, this is the first study in humans that shows this association.