Higher Oxygen Consumption Rate Research Articles

Neuronal Death and Oxidative Stress in the Developing Brain

The developing brain is particularly vulnerable to reactive oxygen and reactive nitrogen species-mediated damage because of its high concentrations of unsaturated fatty acids, high rate of oxygen consumption, low concentrations of antioxidants, high content of metals catalyzing free radical formation, and large proportion of sensitive immature cells. In this review, we outline the dynamic changes of energy resources, metabolic requirements, and endogenous free radical scavenging systems during physiologic brain development. We further discuss the involvement of oxidative stress in the pathogenesis of neuronal death after exposure of the infant brain to hyperoxia, hypoxia/ischemia, sedative drugs, ethanol, and mechanical trauma. Several approaches have been developed to combat oxidative stress, but neuroprotective treatment strategies are limited in the clinical setting.

Oxidative stress in the pathogenesis of neurodegenerative diseases

Oxidative stress is a deleterious condition leading to neuronal cell death. The brain is particularly vulnerable to damage mediated by reactive oxygen and reactive nitrogen species, due to their high concentrations of unsaturated fatty acids, high rate of oxygen consumption, high content of metals catalyzing free radical formation. And finally, the brain is relatively deficient in antioxidant systems with lower activity of glutathione peroxidase and catalase compared to other organs. There is a lot of evidence indicating that oxidative stress plays crucial role in aging as well as in the development and pathology of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. A number of ageing-related neurodegenerative diseases are associated with impaired mitochondrial function, increased oxidative damage, presence of abnormal, aggregated proteins, iron dyshomeostasis, and involvement of excitotoxicity and inflammation. Neurodegenerative disorders are characterized by an abnormal accumulation of oxidatively damaged macromolecules inside the cells and in the extracellular space. The abnormal production by overactivated glial cells of pro-inflammatory cytokines, chemokines and the complement system, as well as reactive oxygen species, can disrupt nerve terminals activity and cause dysfunction and loss of synapses, which correlates with memory decline. This review discusses current knowledge about the involvement of oxidative stress in neurodegenerative diseases pathogenesis, focusing on impaired mitochondrial function, oxidative damage, presence of abnormal, aggregated proteins, iron dyshomeostasis, and functional responses of microglia.

The Forkhead Transcription Factor Hcm1 Promotes Mitochondrial Biogenesis and Stress Resistance in Yeast

In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G(1)/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism.

Indirect effects of an ectoparasite reduce successful establishment of a damselfish at settlement

1. The sublethal impact of parasites on host behaviour and the mechanism linking them to population level effects remain largely unquantified. On the Great Barrier Reef, juvenile gnathiid isopods (mobile ectoparasites) are one of the most common ectoparasites of fishes. Previous laboratory studies on damselfishes suggest that a single gnathiid can kill settlement-stage larvae and very young juveniles, while repeated attacks affect the growth of a juvenile damselfish. Nothing, however, is known of how gnathiids affect the performance, and the survival of settlement stage fishes in the wild. 2. We sampled juveniles of the damselfish Pomacentrus amboinensis for gnathiids and tested the effect of a single gnathiid (Gnathia auresmaculosa) on juvenile survival in the laboratory. We also tested the effect of this gnathiid on the swimming performance, oxygen consumption, and successful establishment in the wild of settlement-stage larvae. 3. Of the juvenile fish sampled at dawn, 3·5% had a gnathiid attached; at other times of the day, fish had no gnathiids. In the laboratory, most gnathiids (79%) remained attached to juvenile fish for up to 6 h and all fish survived exposure to one gnathiid. 4. When tested in pairs in a double-lane swim chamber, fish that had previously been fed on by one gnathiid ceased swimming first in 77% of the trials and had a lower critical swimming speed compared to fish not exposed to a gnathiid. Previously parasitized fish had a 35% higher oxygen consumption rate than did unexposed fish. When tagged fish were placed in pairs on dead coral patches in the wild and monitored, the previously parasitized fish disappeared from the reef first in 67% of the trials. 5. Our analysis indicates that a single ectoparasitic gnathiid isopod significantly decreases the performance of young P. amboinensis and their persistence on the reef. Gnathiids, by affecting fish performance, may therefore indirectly affect the successful establishment of fishes on the reef at settlement, a critical transitional stage for most coral reef fishes. Unsuccessful establishment on the reef most likely increases the interactions of settling fish with predators and thus gnathiids may contribute to the high mortality observed at this time.

Effects of temperature and salinity on oxygen consumption of tawny puffer Takifugu flavidus juvenile

The respiratory rates of Tawny puffer Takifugu flavidus juvenile were measured at four temperatures (20, 23, 26 and 29 °C) and seven salinities (5, 10, 15, 20, 25, 30 and 35 g L−1). The results showed that both temperature and salinity significantly affected the oxygen consumption of tawny puffer juvenile. The oxygen consumption rate (OCR) increased significantly with an increase in the temperature from 20 to 29 °C. Over the entire experimental temperature range (20–29 °C), the Q10 value was 1.59, and the lowest Q10 value was found between 23 and 26 °C. The optimal temperature for the juvenile lies between 23 °C and 26 °C. The OCR at 25 g L−1 was the highest among all salinity treatments. The OCRs show a parabolic relationship with salinity (5–35 g L−1). From the quadratic relationship, the highest OCR was predicted to occur at 23.56 g L−1. The optimal salinity range for the juvenile is from 23 to 25 g L−1. The results of this study are useful towards facilitating an increase in the production of the species juvenile culture.

Net dissolved inorganic nitrogen production in hyporheic mesocosms with contrasting sediment size distributions

The interstitial spaces within streambeds are recognized as an important location of dissolved inorganic nitrogen (DIN) transformations in streams. However, it remains uncertain how physical characteristics of streambeds affect the magnitude and net outcome of subsurface nitrogen transformations. We tested whether the size distribution of streambed sediments, in isolation from the influence of streambed topography and groundwater upwelling, could affect net DIN uptake or production along interstitial flow paths. Mesocosms constructed from PVC pipe (15 cm diameter × 1 m long) were filled with either coarse gravel/cobble or gravel/cobble mixed with finer sediments (5 mesocosms per sediment treatment). Mesocosms were submerged in a stream and oriented, so that surface water flowed through the sediments. After 2 months incubation, we measured DIN in interstitial water at 20 cm intervals and dissolved oxygen at 10 cm intervals along mesocosm flow paths. In both sediment types, DIN concentrations increased longitudinally along mesocosm flow paths in the direction of interstitial flow, indicating net DIN production. Although DIN increased to higher concentrations in mesocosms with fine sediments, greater exchange flow through coarse sediments resulted in similar rates of net DIN production and delivery to surface water. Production of DIN in both sediment types was concentrated within the first 10 cm of interstitial flow paths, with no significant production further along the flow paths. Coarse sediments had higher rates of oxygen consumption per unit sediment volume than the coarse–fine sediment mix, suggesting interstitial water velocity may be an important factor affecting hyporheic microbial metabolism.

Mercury in canned tuna: The importance of selenium

To the Editor: The recent article by Gerstenberger et al. [1], reported the mercury (Hg) concentrations, but did not report the selenium (Se) contents of the tuna. Since methylmercury is, by biochemical definition, a highly specific irreversible inhibitor of Se-dependent enzymes [2], it is necessary to measure both Hg and Se to accurately assess risks associated with Hg exposures. The brain and neuroendocrine tissues depend upon Se-dependent enzymes to prevent and reverse oxidative damage that would otherwise accompany their high rates of oxygen consumption. Because the affinity of Hg for Se is approximately a million times higher than its affinity for sulfur [3], the Seenzymes are uniquely vulnerable to inhibition by high methylHg exposures. However, rather than impairing Se enzymes, eating ocean fish such as tuna that are known to provide far more Se than Hg actually enhances nutritional Se status, explaining why ocean fish consumption has repeatedly been shown to prevent, rather than contribute to Hg toxicity [2]. In contrast, consumption of meats of predatory whales and sharks that are known to contain far more Hg than Se has been shown to be hazardous. Current U.S. Environmental Protection Agency (U.S. EPA) risk criteria are based on a study of human Hg exposures that arose predominantly from eating pilot whale meats. Since pilot whale meats are virtually unique in having exceedingly high Hg to Se molar ratios (5:1), as well as Hg contents in excess of 3 ppm [4], this is clearly a food to avoid. In contrast, ocean fish are Se-rich and have Hg to Se molar ratios that are typically on the order of 1:5, which may explain why ocean fish consumption has been shown to counteract Hg toxicity from whale meat consumption [5]. Although blood Hg and blood Hg to Se molar ratios in children exposed in utero are highly correlated [6], relationships between Hg exposures and risk are most accurately predicted from the perspective of Hg to Se molar ratios. Therefore, the selenium-health benefit value (Se-HBV) is preferable since it incorporates both the relative and the absolute amounts of Se intake and Hg exposure in a single criterion. Health benefits are directly associated with positive Se-HBVs, whereas adverse health effects are directly proportional to negative Se-HBVs [2]. Since methylmercury is an enzyme inhibitor, its chemical reactions are clearly second order. Therefore, attempting to

Climatic forcing of eastern Mediterranean deep-water formation and benthic ecosystems during the past 22 000 years

Lateglacial and Holocene faunal and stable-isotope records from benthic foraminifers in the eastern Mediterranean Sea (EMS) suggest a high spatiotemporal variability of deep-water oxygenation and biogeochemical processes at the sea floor during that time. Changes in the oxygenation and food availability of the deep-sea ecosystems are closely linked to the hydrology of the EMS borderlands; they reflect orbital and suborbital climate variations of the high northern latitudes and the African monsoon system. During the last glacial maximum, cool surface waters and high evaporation resulted in maximum convection and oxic deep-waters in all sub-basins. Strong wind-induced mixing fostered surface-water production with seasonal phytodetritus fluxes. During the glacial termination and the Holocene, oxygenation and food availability of deep-sea benthic ecosystems were characterized by a pronounced regional differentiation. Local deep-water formation and trophic conditions were particularly variable in the northern Aegean Sea as a response to changes in riverine runoff and Black Sea outflow. During the interval of sapropel S1 formation in the early Holocene, average oxygen levels decreased exponentially with increasing water depth, suggesting a basin-wide shallowing of vertical convection superimposed by local signals. In the northernmost Aegean Sea, deep-water ventilation persisted during the early period of S1 formation, owing to temperature-driven local convection and the absence of low-salinity Black Sea outflow. At the same time, severe temporary anoxia occurred in the eastern Levantine basin at water depths as shallow as 900 m. This area was likely influenced by enhanced nutrient input of the Nile river that resulted in high organic matter fluxes and related high oxygen-consumption rates in the water column. In the southern Aegean and Levantine Seas, we observe a gradual increase in deep-water residence times, preceding S1 formation by approximately 1–1.5 kyr. Once oxygen levels fell below a critical threshold, the benthic ecosystems collapsed almost synchronously with the onset of S1 deposition. The recovery of benthic ecosystems during the terminal phase of S1 formation is controlled by subsequently deeper convection and re-ventilation over a period of approximately 1500 years. After the re-ventilation of the various sub-basins had been completed during the middle and late Holocene, deep-water renewal was more or less similar to recent rates. During that time, deep-sea ecosystem variability was driven by short-term changes in food quantity and quality as well as in seasonality, all of which are linked to millennial-scale changes in riverine runoff and associated nutrient input.

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents

To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents. The glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity potential was evaluated in DIO mice. OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice. OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity.

EFFECT OF HYDROGEN ION AND OXYGEN CONCENTRATIONON RESPIRATION PHYSIOLOGY ON SEAWATER SNAILPLANAXIS SULCATUS

The effect of some exogenous factors such as oxygen concentration and hydrogen ions concentration on the rate of oxygen consumption of seawater snail Planaxis sulcatus . This study was designed in Marine Sciences station (Aqaba) during the period September 2000 to October 2001 . High weight specific oxygen consumption rate was observed at pH range 7 to 8 (135.245_ 119.717μl. gˉ¹ . hrˉ ¹) respectively. The results showed that Any deviation from this range toward more acidic or alkaline pH reduced the oxygen consumption rate. The intertidal snail were oxygen conformers since their oxygen consumption rate was oxygen concentration dependent at least at high oxygen concentration thus, the weight specific oxygen consumption rate was increasing from as a result of increasing the oxygen concentration from 20 to 100% oxygen saturation .

STUDIES ON THE OXYGEN CONSUMPTION RATE AND ASPHYXIANT POINT OF <I>MEGALOBRAMA PELLEGRINI</I> AND <I>COREIUS GUICHCNOTI</I>

Both of Megalobrama pellegrini and Coreius guichcnoti are endemic fish in the upper reach of Yangtze River(from Yichang to Yibin).The construction of the hydroelectric projects,such as the Gezhouba Dam,the Three Gorges Dam,and hydropower cascade exploitation in the Jinsha River,drastically modifies physical environment and regulates flow in the Yangtze River course.This causes the habitats fragmentation to fish,blocks their migration routes,and destroys their spawning grounds,leading to the severe negative impacts on the rare and endemic fishes of the Yangtze River.Due to these reasons,it is forecasted that the population of these two kinds of fish might decrease sharply in the future.It becomes very urgent to take suitable countermeasures for conservation and resource-recovery.The oxygen consumption rate(OCR) and asphyxiant point(AP) are the important physiological indexes to fish culturing and breeding.In this experiment,the OCR and AP of these two kinds of fish were investigated by means of determining the dissolved oxygen in water.The method of respiratory chambers which were self-made had been applied.Two kinds of these experiment apparatus were used,one was done in sealed-still water,the other was done in sealed-flowing water.The temperature in the sealed respiratory chamber could be controlled.The oxygen consumption rate and the effect of body weight on the asphyxiant point of Megalobrama pellegrini were studied.The results demonstrated that,under the controlled temperature(15—27 ℃),the oxygen consumption rate of M.pellegrini increased while temperature rose,and decreased while body weight increased.The relationship between oxygen consumption rate and temperature can be described as y=0.036x-0.281(R2= 0.669,P0.01,n=15).The asphyxiant point decreased while body weight increased,but there was no significant difference(P0.05).The oxygen consumption rate of this fish ranged from 0.28 mg/g·h to 0.82 mg/g·h.In the temperature of 24.8 ℃,the fish that weight 1.3—3.2 g had a mean asphyxiation point of(0.91±0.08) mg/L and the range was 0.73—1.04 mg/L.The day and night change of oxygen consumption rate was studied on C.guichcnoti.The highest and lowest of the daily fluctuation of the oxygen consumption rate occurred at 3:00 and 21:00 respectively.The average oxygen consumption rate at night was much higher than that in the daytime.The result showed that this fish was more active at night.This phenomenon was identical with practice,and we found that this fish fed in night and slept in day.The fish that weight 21.8—46.3 g had a range of oxygen consumption rate from 0.64 mg/g·h to 0.18 mg/g·h under 23—27 ℃.The oxygen consumption rate decreased while the body weight of this fish increased.The relationship between oxygen consumption rate and body weight can be described as y=14.33x-1.08(R2=0.545,P0.01,n=21).The asphyxiant point of this fish was 0.95—1.63 mg/L,and the mean was(1.14±0.23) mg/L.Both of these two fish had high oxygen consumption rate and asphyxiant point.The results showed that the ability of low oxygen endurance of these two fish were much feeble than that of other fish.The present study can provide the basis of rational stocking,water quality management,bait feeding and transportation of live fish in artificial culturing production.

The effect of environmental factors on filtration and the oxygen consumption rate of the rotifer Brachionus plicatilis: a primary exploration of red tide control

The effect of environmental factors on filtration and the oxygen consumption rate of the rotifer Brachionus plicatilis: a primary exploration of red tide control To evaluate the potential to control red tides using the mass-cultured heterotrophic grazer, rotifer Brachionus plicatilis, the effects of environmental factors (water temperature and salinity) on physical activities (filtration and oxygen consumption rate) of B. plicatilis were estimated. Experiments were conducted at different water temperatures (15, 20, 25, 30 and 35°C) and salinities (20, 25, 30, 35 and 40 PSU), in 25 different combinations (5 temperatures × 5 salinities). Results showed that water temperature and salinity had significant effects on the filtration rate of B. plicatilis (F=41.66, P<0.05). The results of multiple regression analysis yielded the following functional dependence of filtration rate (F) on water temperature (T) and salinity (S): F=-1.658+0.917 T+0.63S (R2=0.769, P<0.001). The highest filtration rate (4.23 ±0.74 μl rot-1 h-1) was obtained at 30°C and salinity 35 PSU, and the lowest one (0.869 ±0.13 μl rot-1 h-1) was observed at 15°C and salinity 20 PSU. Both water temperature and salinity had significant effects on the oxygen consumption rate of B. plicatilis (F=34.08, P<0.05). The results of multiple regression analysis yielded the following functional dependence of oxygen consumption rate (O) on water temperature (T) and salinity (S): O=-3.133+0.165T+0.81S (R2=0.938, P<0.001). The highest oxygen consumption rate (5.38 ±0.66 ng rot-1 h-1) was observed at 35°C and salinity 40 PSU, and the lowest one (1.01 ±0.15 ng rot-1 h-1) was observed at 15°C and salinity 20 PSU. Results from this present study indicated that the filtration and oxygen consumption rate of the rotifer were significantly influenced by the water temperature and salinity. The utilization of rotifer for red tide control has to consider the influence of environmental factors.

In Yarrowia Lipolityca Mitochondria the Association of NADH Dehydrogenase Type II with the Cytochrome Complexes Depends on the Growth Phase

In Yarrowia lipolytica mitochondria, the electron transport from NADH to O2 is branched by alternative respiratory components. One external NADH dehydrogenase (NDH2e) and an alternative oxidase (AOX). Both enzymes are peripheral single-subunit oxido-reductases not implicated in proton gradient formation. Thus, if electrons pass through those two enzymes, the oxidation of NADH is not able to conserve energy. During exponential growth, this is undesirable; however, during the stationary phase this process may help to maintain a high rate of oxygen consumption. To prevent the electron flux between alternative components, either AOX may be interacting with the complex I or NDH2e with complexes III and IV. We have evaluated the participation of the alternative components on electron transport and on supramolecular structures of mitochondria from wild type and a αnubm mutant, where complex I is inactive and NDH2 was redirected to the matrix side (NDH2i)4. In order to determine whether there are specific interactions between NDH2e and other respiratory complexes, we measured oxygen consumption rates with different respiratory substrates and inhibitors. We suggested an interaction of NDH2e (but not NDH2i) with cytochrome complexes, indicating that the interaction sites are located in the intermembrane face of the cytochromic complexes. Furthermore, we identified by native PAGE, in-gel activity and mass spectrometry this interaction between NDH2e with complexes III and IV in the wild type. Also, larger supercomplexes5 and a complex V dimer were found. This association pattern seems to vary during the stationary phase as NDH2e is overproduced saturating its binding site in Cyt IV and thus appearing as the free enzyme.

Estimation of salivary protein thiols and total antioxidant power of saliva in brain tumor patients

The role of oxidative stress in the genesis of various types of cancers is well established. Several chemical, cell culture and animal studies also indicate that antioxidants may slow or even prevent the development of cancer. Brain is considered abnormally sensitive to oxidative damage as brain tissue has high rate of oxygen consumption, high lipid content and relatively low antioxidant defenses, compared to other tissues. The study design chosen for the present study was cross sectional. The biochemical parameters that were estimated in saliva manually using spectrophotometric methods were ferric reducing antioxidant power (FRAP) assay--a direct measure of total antioxidant activity of biological fluids and protein thiols. The physical parameters of saliva that were also assessed were salivary flow rate, pH of the saliva and the osmolality of the saliva. The mean values of salivary flow rate and pH were significantly decreased among malignant and benign tumor patients whereas the salivary osmolality was significantly increased in both the groups of patients. The mean values of salivary FRAP were significantly reduced among malignant and benign tumor patients. However, the salivary protein thiols were significantly increased in these patients. Hence with these observations it can be concluded that in saliva, besides the physical characteristics, salivary FRAP and protein thiol levels are appropriate indicators of the antioxidant status in brain tumor patients.

J0202-2-1 微細構造を有する平板型高密度バイオリアクター([J0202-2]バイオ熱・物質移動(2))

An engineered tissue performing in-vivo physiological metabolic rate should keep cellular density around 10^8〜10^<10> cells/mL, which is far higher than that of normal dish culture. This study proposes a perfusion culture plate with designed microstructure allowing HepG2 cells of 10^7〜10^8 cells/mL to adhere on the plate. The total oxygen metabolic rate of the bioreactor was calculated using the cellular adhesion ratio to fluid shear flow stress and the single cellular oxygen metabolic rate. The measured oxygen metabolic rate is lower than the calculated values, although the trends of oxygen metabolic rate to perfusion flow rate for both measured and calculated are similar. It is suspected that the cellular high oxygen consumption rate in the still medium in the bioreactor might lead to lethal hypoxic condition in a short time before starting the perfusion.

The effects of low oxygen on self-renewal and differentiation of embryonic stem cells

To summarize recent reports on the effects of low oxygen on the undifferentiated phenotype and differentiation of embryonic stem cells (ESCs). The oxygen level to which ESCs are exposed is an important environmental parameter. Under conditions maintaining the undifferentiated phenotype, low oxygen reduces spontaneous differentiation of human ESCs but reduces pluripotency gene expression in mouse ESCs, although reports are conflicting. Differentiation under low oxygen increases generation of neurons, cardiomyocytes, hematopoietic progenitors, endothelial cells, and chondrocytes. Many of the effects of low oxygen have been attributed to action by hypoxia inducible factor-1alpha (HIF-1alpha). The oxygen level in the gas phase (pO2gas) is often different than that experienced by the cells (pO2cell) and is unrecognized by investigators, which makes interpretation of the literature difficult. This difference increases with high cell densities, high cellular oxygen consumption rates, and large medium heights. The problem can be addressed by use of oxygen-permeable culture dishes and by estimation of pO2cell with mathematical models. Low oxygen influences aspects of ESC pluripotency and differentiation. A better understanding of its effects and mechanism along with better estimation and control of pO2cell is important for applying low oxygen culture to regenerative medicine applications.

Expression of Ankyrin Repeat and Suppressor of Cytokine Signaling Box Protein 4 (Asb-4) in Proopiomelanocortin Neurons of the Arcuate Nucleus of Mice Produces a Hyperphagic, Lean Phenotype

Ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 (Asb-4) is specifically expressed in the energy homeostasis-related brain areas and colocalizes with proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC). Injection of insulin into the third ventricle of the rat brain increased Asb-4 mRNA expression in the paraventricular nucleus but not in the ARC of the hypothalamus, whereas injection of leptin (ip) increased Asb-4 expression in both mouse paraventricular nucleus and ARC. A transgenic mouse in which Myc-tagged Asb-4 is specifically expressed in POMC neurons of the ARC was made and used to study the effects of Asb-4 on ingestive behavior and metabolic rate. Animals with overexpression of Asb-4 in POMC neurons demonstrated an increase in food intake. However, POMC-Asb-4 transgenic animals gained significantly less weight from 6-30 wk of age. The POMC-Asb-4 mice had reduced fat mass and increased lean mass and lower levels of blood leptin. The transgenic animals were resistant to high-fat diet-induced obesity. Transgenic mice had significantly higher rates of oxygen consumption and carbon dioxide production than wild-type mice during both light and dark periods. The locomotive activity of transgenic mice was increased. The overexpression of Asb-4 in POMC neurons increased POMC mRNA expression in the ARC. The transgenic animals had no observed effect on peripheral glucose metabolism and the activity of the autonomic nervous system. These results indicate that Asb-4 is a key regulatory protein in the central nervous system, involved in the control of feeding behavior and metabolic rate.

Ataxia telangiectasia mutated activation by transcription‐ and topoisomerase I‐induced DNA double‐strand breaks

Ataxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is a crucial mediator for the DNA damage response (DDR). As neurons have high rates of transcription that require topoisomerase I (TOP1), we investigated whether TOP1 cleavage complexes (TOP1cc)-which are potent transcription-blocking lesions-also produce transcription-dependent DNA double-strand breaks (DSBs) with ATM activation. We show the induction of DSBs and DDR activation in post-mitotic primary neurons and lymphocytes treated with camptothecin, with the induction of nuclear DDR foci containing activated ATM, gamma-H2AX (phosphorylated histone H2AX), activated CHK2 (checkpoint kinase 2), MDC1 (mediator of DNA damage checkpoint 1) and 53BP1 (p53 binding protein 1). The DSB-ATM-DDR pathway was suppressed by inhibiting transcription and gamma-H2AX signals were reduced by RNase H1 transfection, which removes transcription-mediated R-loops. Thus, we propose that Top1cc produce transcription arrests with R-loop formation and generate DSBs that activate ATM in post-mitotic cells.

Effect of body weight and acclimated temperature on the respiration physiology on seawater snail Planaxis sulcatus

This study was designed in Marine Sciences station (Aqaba) during the period September 2000 to October 2001 . The study of the effect of body weight on the metabolic rate revealed the presence of a proportional relationship between the metabolic and body weight and the presence of inverse relationship between the metabolic and body weigh.In snails acclimated to 10 ºC, 20 ºC, and 30 ºC, the Weight specific metabolic rate was influenced by both acclimation as well as experimental temperature. Thus, the oxygen consumption rate increased 1n 10 ºC acclimated snail from 44 µl O2. gˉ¹ . hrˉ ¹ to 105 µl O2. gˉ¹ . hrˉ ¹ As a result of increasing the experimental temperature from 10 ºC to 30. ºC In 20 and 30 ºC acclimated snail, and as a result of increasing the experimental temperature from 10 to 30, the weight specific oxygen consumption rates increased (20 ºC and 30 ºC ) from 40 µl O2. gˉ¹ . hrˉ ¹ to 88 and 35 to 85 µl O2. gˉ¹ . hrˉ ¹ Respectively. Snails acclimated to 10 ºC ,20 ºC and 30 ºC showed Precht s type 3 normal the(partial) compensation in weight specific oxygen consumption rate , since at all experiment temperatures , the highest oxygen consumption rate was observed in 10 ºC Acclimated animals, whereas the lowest rate was observed in 30 ºC acclimated snails.

Effects of Acetate on Lipid Metabolism in Muscles and Adipose Tissues of Type 2 Diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

We have reported that orally administrated acetate contributed to suppression of lipogenesis in the liver and to reduction of lipid accumulation in the adipose tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The aim of this study was to investigate the effect of acetate on skeletal muscle and adipose tissues. Treatment with acetate showed a higher rate of oxygen consumption and a smaller size of lipid droplets in white adipose and brown adipose tissues. An analysis by Northern blotting revealed that the transcripts of myoglobin and Glut4 genes in the abdominal muscle of the OLETF rats were increased by acetate treatment, while the transcripts of lipolytic genes increased in the white adipose and brown adipose tissues. It is possible that acetate has effects on lipid metabolism in the skeletal muscles and the adipose tissues, and has functions that work against obesity and obesity-linked type 2 diabetes.