On the relationship between the mitochondrial inner membrane anion channel and the adenine nucleotide translocase

The mitochondrial inner membrane anion channel (IMAC) is a transport pathway which is believed to be involved in mitochondrial volume homeostasis. The protein, however, has not been identified. In this paper, we examine the relationship between IMAC and the adenine nucleotide translocator. Many inhibitors of the adenine nucleotide translocase are shown to block IMAC, including Cibacron blue 3GA, bromcresol green, alizarin red S, agaric acid, palmitoyl-CoA, and the fluorescein derivatives erythrosin B, erythrosin isothiocyanate, rose bengal, and eosin Y. The following evidence suggests that Cibacron blue, agaric acid, and palmitoyl-CoA inhibit by binding to a common site. 1) They all only partially block the transport of small anions such as Cl-, NO3-, and HCO3-, but completely block the transport of larger anions such as malonate. 2) They decrease the IC50 values of each other in a manner consistent with competitive binding. 3) N-Ethylmaleimide decreases their IC50 values by a similar extent. 4) Inhibition by all shows no dependence on matrix pH and only a small dependence on medium pH. It is suggested that these agents may selectively bind to an open state of IMAC and inhibit by decreasing its conductance. The physiological nucleotides CoA, NAD+, NADH, NADP+, NADH, and ATP do not inhibit; in fact, IMAC is shown to transport ATP. Despite these similarities between IMAC and the adenine nucleotide translocase, IMAC appears to be a separate entity, since some of the IC50 values differ by up to 8-fold, and carboxyatracyloside, the most selective inhibitor of the adenine nucleotide translocase, has no effect on IMAC. In addition, IMAC is also able to transport AMP, while the adenine nucleotide translocase does not.     

Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes

The initial suspicion that obesity increases coronary risk has been much sharpened with the demonstration that risk is more tightly linked to abdominal than to peripheral obesity, and tighter yet again when the mass of omental adipose tissue is taken into account. These data suggest that important metabolic differences might exist between adipocytes from different regions, and indeed, it has long been appreciated that triacylglycerol hydrolysis can be stimulated to a greater extent in omental than in subcutaneous adipocytes. The present study focuses on triacylglycerol synthesis in human subcutaneous and omental adipocytes, a process which, by contrast, has received relatively little attention. Experiments were done on adipose tissue removed at laparotomy and on cultured preadipocytes. With the former, triacylglycerol synthesis was measured in the presence and absence of oleate added to the medium using radiolabeled glucose and oleate as tracers. The results demonstrate that under all conditions examined triacylglycerol synthesis in subcutaneous adipose tissue exceeded that in deep omental adipose tissue. To study the cells in more detail, preadipocytes were cultured and triacylglycerol synthesis was examined again under basal conditions and with stimulation with insulin and acylation stimulating protein (ASP). Under basal conditions, particularly when oleate was added to the medium, clear differences were present such that triacylglycerol synthesis was substantially greater in subcutaneous preadipocytes than in omentally derived preadipocytes. These differences were more pronounced when the cells were stimulated with either insulin or acylation stimulating protein. Overall, triacylglycerol synthetic capacity in subcutaneous tissue exceeded that in omental tissue. As a consequence, omental tissue as compared to subcutaneous adipose tissue would have a limited capacity to prevent fatty acids from reaching the liver and stimulating hepatic lipoprotein synthesis.     

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.     

Characterization and variability of endotoxin and 3-hydroxy fatty acids in an office building during a particle intervention study

Air and dust samples were collected on two floors of an office building during a double-blind particle intervention study to examine spatial and temporal variability of airborne endotoxin over a period of weeks, and to characterize endotoxin activity and lipopolysaccharide (LPS) content in carpet and chair dust. Air samples were collected on multiple days within and across weeks. Dust samples were collected from carpets and chairs one day per week for three weeks. Endotoxin was measured using a Limulus assay. Dust samples were analyzed for LPS by determination of 3-hydroxy fatty acids (3-OHFAs) using gas chromatography-mass spectrometry. The geometric mean (geometric standard deviation) for 96 indoor air samples was 0.24 (1.6) EU/m3. Significant within-floor spatial variation of airborne endotoxin was found (P < 0.0001, n = 80). Temporal variability of airborne endotoxin was not significant across weeks. Mean (+/- SD) endotoxin levels in carpet dust (59 +/- 9.3 EU/mg dust, n = 12) and in chair dust (38 +/- 7.7 EU/mg dust, n = 10) were significantly different (P < 0.001). Carbon chain length-dependent differences in 3-OHFA levels by dust source and floor were found. Enhanced air filtration did not significantly affect airborne endotoxin (P = 0.62); however, total dust mass and total endotoxin in carpet dust samples increased significantly after enhanced surface cleaning (P < 0.01). These findings suggest that spatial variability, dust source, and surface cleaning may influence building occupant exposures to endotoxin.     

Influence of chemical and biological factors on trophic transfer of persistent organic pollutants in the northwater polynya marine food web

Persistent organic pollutants (POPs) and stable isotopes of nitrogen (delta 15N) were measured in zooplankton (6 species), a benthic invertebrate (Anonyx nugax), Arctic cod (Boreogadus saida), seabirds (6 species), and ringed seals (Phoca hispida) collected in 1998 in the Northwater Polynya to examine effects of biological and chemical factors on trophic transfer of POPs in an Arctic marine food web. Strong positive relationships were found between recalcitrant POP concentrations (lipid corrected) and trophic level based on stable isotopes of nitrogen, providing clear evidence of POP biomagnification in Arctic marine food webs. Food web magnification factors (FWMFs), derived from the slope of the POP--trophic level relationship, provided an overall magnification factor for the food web but over and underestimated biomagnification factors (BMFs) based on predator--prey concentrations in poikilotherms (fish) and homeotherms (seabirds and mammals), respectively. Greater biomagnification in homeotherms was attributed to their greater energy requirement and subsequent feeding rates. Within the homeotherms, seabirds had greater BMFs than ringed seals, consistent with greater energy demands in birds. Scavenging from marine mammal carcasses and accumulation in more contaminated winter habitats were considered important variables in seabird BMFs. Metabolic differences between species resulted in lower than expected BMFs, which would not be recognized in whole food web trophic level--POP relationships. The use of sigma POP groups, such as sigma PCB, is problematic because FWMFs and BMFs varied considerably between individual POPs. FWMFs of recalcitrant POPs had a strong positive relationship with log octanol--water partition coefficient (Kow). Results of this study show the utility of using delta 15N to characterize trophic level and trophic transfer of POPs but highlight the effects of species and chemical differences on trophic transfer of POPs that can be overlooked when a single magnification factor is applied to an entire food web.     

Automatic Flow-Control Adaptation for Enhancing Network Performance in Computational Grids

With the advent of computational Grids, networking performance over the wide-area network (WAN) has become a critical component in the Grid infrastructure. Unfortunately, many high-performance Grid applications only use a small fraction of their available bandwidth because operating systems and their associated protocol stacks are still tuned for yesterday's WAN speeds. As a result, network gurus undertake the tedious process of manually tuning system buffers to allow TCP flow control to scale to today's WAN Grid environments. And although recent research has shown how to set the size of these system buffers automatically at connection set-up, the buffer sizes are only appropriate at the beginning of the connection's lifetime. To address these problems, we describe an automated and lightweight technique called dynamic right-sizing that can improve throughput by as much as an order of magnitude while still abiding by TCP semantics.