Hepatic Gluconeogenesis and the Activity of PDH in Individual Tissues of GTG-Obese Mice Following Adrenalectomy

Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 ± 0.7g; GTG: 44.1 ± 0.4g; p<0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 ± 1.6 mmol/L; GTG: 29.4 ± 1.9 mmol/L; p<0.05) and serum insulin levels (GTG ADX: 76 ± 10μ.U/mL; GTG: 470 ± 63μU/mL; p<0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 ± 10 nmol glucose/10⁶ cells; GTG: 403 ± 65 nmol glucose/10⁶ cells; p<0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 ± 27 μmol/liver; GTG: 614 ± 60 pmol/Iiver; p<0.05) and fatty acid content (GTG ADX: 101 ± 9 mg fatty acid/g liver; GTG: 404 ± 40 mg fatty acid/g liver; p<0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.     

Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum

Isoflavonoids are compounds present in many legumes, but are derived in the human diet mainly from soybeans and various soybean-based food products. The major isoflavonoids occurring in soy are the glycosides of genistein and daidzein. The metabolic products of genistein metabolism in humans have not been clearly shown. The two main products of daidzein metabolism in humans appear to be equol and O-desmethylangolensin. Increasing evidence suggests that oxidative modification to low-density lipoprotein is involved in atherogenesis, and that natural antioxidants that prevent or inhibit oxidative damage to low-density lipoprotein may beneficially influence atherogenesis. In the present experiments, the effects of genistein and daidzein, and the daidzein metabolites equol and O-desmethylangolensin on Cu²⁺-induced oxidation of lipoproteins in serum were examined. Three concentrations of each compound (0.1 μM, 1 μM, 10 μM) were tested for antioxidant activity in six individual serum samples. All compounds tested inhibited lipoprotein oxidation. The minimum concentration for significant inhibition was 1 μM for genistein and daidzein (P < 0.05), and 0.1 μM equol and O-desmethylangolensin (P < 0.05). Equol and O-desmethylangolensin were more potent inhibitors of in vitro lipoprotein oxidation in serum than the two major dietary isoflavonoids. This study has demonstrated that soybean isoflavonoids and metabolic products of daidzein metabolism inhibit lipoprotein oxidation in vitro. Human intervention studies are needed to determine if these compounds can influence oxidation in vivo.     

Extracellular addition of a domain of HIV-1 Vpr containing the amino acid sequence motif H(S/F)RIG causes cell membrane permeabilization and death

Vpr is a virion-associated protein of human immuno-deficiency virus type 1 (HIV-1) whose function in acquired immune deficiency syndrome (AIDS) has been uncertain. We previously employed yeast as a model to examine the effects of Vpr on basic cellular functions; intracellular Vpr was shown to cause cell-growth arrest and structural defects, and these effects were caused by a region of Vpr containing the sequence HFRIGCRHSRIG. Here we show that peptides containing the H(S/F)RIG amino acid sequence motif cause death when added externally to a variety of yeast including Saccharomyces cerevisiae, Kluyveromyces lactis, Candida glabrata, Candida albicans and Schizosaccharomyces pombe. Such peptides rapldly entered the cell from the time of addition, resulting in cell death. Elevated levels of ions, particularly magnesium and calcium ions, abrogated the cytotoxic effect by preventing the Vpr peptides from entering the cells. Extracellular Vpr found in the serum, or breakdown products of extracellular Vpr, may have similar effects to the Vpr peptides described here and could explain the death of uninfected by-stander cells during AIDS.     

Reproductive strategies of Atlantic salmon: ecology and evolution

Atlantic salmon (Salmo solar, Salmonidae) show a diversity of life history, behavioural and morphological adaptations for reproduction which have evolved as an outcome of competition to maximize reproductive success. Reproductive traits of females have been shaped principally by natural selection for offspring production and survival, those of males by sexual selection for access to matings. Female Atlantic salmon invest approximately six times more energy in offspring production (i.e. gonads) than males and face an important trade-off between number and size of eggs to produce that will maximize the number of surviving offspring. Timing of breeding and the construction of nests appear adapted to increase offspring survival. The most important determinant of female breeding success is body size because it affords high fecundity, access to breeding territories and decreased probability of nest destruction. Asynchronous female spawning and the male ability to spawn rapidly and repeatedly results in male-biased operational sex ratios that generate intense male competition for mates. This has likely been responsible for the evolution of elaborate male secondary sexual characters associated with fighting and status signalling. Furthermore, it has given rise, through frequency-dependent selection, to two alternative male breeding phenotypes: (1) large, anadromous males; and (2) small, mature male parr. Anadromous males invest heavily in behavioural activity on the spawning grounds, searching and fighting for mates and courting them, with body size being an important determinant of their breeding success. This behavioural activity carries a heavy cost, as anadromous males have significantly reduced survival relative to females. In contrast, mature male parr invest proportionally more in testes for sperm competition and attempt to sneak access to matings. While this behaviour also carries costs in terms of subsequent growth and survival, male parr are more likely to breed again, either prior to or following a migration to sea, than anadromous males. While knowledge about the breeding of Atlantic salmon is detailed, we are only beginning to understand the ultimate causes and/or functional significances of their reproductive strategies. Predictive models of the life history variation are developing, focusing on the need for empirical study and testing of life history and reproductive patterns.     

Nationalism and Belonging in India,Pakistan and South Central Asia: Some Comparative Observations

The criteria invoked in the definition of national identity are commonly derived from contexts other than those of the nation-state itself—most notably those of territoriality, language/culture, kinship/descent and religion. It therefore follows that in seeking to understand the kind of identity or belongingness invoked in a particular instance of national ideology it is necessary to explore not only the kind of nation-state envisaged, but also those non-national forms of belonging or community from which the national ideology may itself be historically derived. In this paper I seek to develop this argument by comparing some of the principal forms of nationalism found in India, Pakistan and Central Asia. I pay particular attention to the importance of the concept qawm, which in Pakistan, Afghanistan and elsewhere in Central Asia, is used to refer to a wide variety of groups to which people owe allegiance. Such usages alert us to the important fact that the nation, as ‘imagined community’, may have its origins as a political movement among sentiments and allegiances which draw on pre-modern social arrangements and are in tension with ‘nationalist’ exclusivism. Even when the nation (as nation-state) has been secured, so-called ‘nationalist’ revivalism, while taking the nation for granted, may in fact appeal to sentiments of a different kind.