Magnesium-induced inner membrane aggregation in heart mitochondria: prevention and reversal by carboxyatractyloside and bongkrekic acid

Mg(2+) at an optimal concentration of 2mM (ph 6.5) induces large increases (up to 30 percent) in the optical density of bovine heart mitochondria incubated under conditions of low ionic strength (< approx. 0.01). The increases are associated with aggregation (sticking together) of the inner membranes and are little affected by changes in the energy status of the mitochondria. Virtually all of a number of other polyvalent cations tested and Ag(+) induce increases in mitochondrial optical density similar to those induced by Mg(2+), their approximate order of concentration effectiveness in respect to Mg(2+) being: La(3+) > Pb(2+) = Cu(2+) > Cd(2+) > Zn(2+) > Ag(+) > Mn(2+) > Ca(2+) > Mg(2+). With the exception of Mg(2+), all of these cations appear to induce swelling of the mitochondria concomitant with inner membrane aggregation. The inhibitors of the adenine nucleotide transport reaction carboxyatratyloside and bongkrekic acid are capable of preventing and reversing Mg(2+)-induced aggregation at the same low concentration required for complete inhibition of phosphorylating respiration, suggesting that they inhibit the aggregation by binding to the adenine nucleotide carrier. The findings are interpreted to indicate (a) that the inner mitochondrial membrane is normally prevented from aggregating by virtue of its net negative outer surface change, (b) that the cations induce the membrane to aggregate by binding at its outer surface, decreasing the net negative charge, and (c) that carboxyatractyloside and bongkrekic acid inhibit the aggregation by binding to the outer surface of the membrane, increasing the net negative charge.     

Inhaling and lung cancer: an anomaly explained.

An objective index of inhaling cigarette smoke based on carboxyhaemoglobin concentrations and the carbon monoxide yields of cigarettes was used to investigate possible systematic differences in the extent of inhaling among light and heavy smokers when classified according to their self described inhaling habits. A total of 2108 men who smoked cigarettes were studied. Heavy smokers (20 or more cigarettes a day) had a higher average inhaling index than light smokers (fewer than 20 cigarettes a day) both among those who said that they inhaled and among those who said that they did not. This observation, together with indirect evidence that heavy smokers who inhale deeply may to some extent avoid depositing smoke condensate on their main bronchial epithelium, explains a hitherto unresolved anomaly--namely, that the risk of lung cancer is less among heavy cigarette smokers who say that they inhale than it is among those who say that they do not inhale.     

Effect of metformin on insulin receptor binding and glycaemic control in type II diabetes.

To investigate the effect of metformin on insulin receptor binding and diabetic control, eight obese type II diabetic patients were studied before treatment, after one and four weeks of taking metformin (500 mg thrice daily), and four weeks after withdrawal of the drug. After one and four weeks of treatment the number of erythrocyte insulin receptors had increased by 116% and 184% respectively. This was due almost entirely to an increase in the number of low affinity binding sites. The number of receptors was still raised four weeks after metformin had been withdrawn. Diabetic control as assessed by urinary glucose, glycosylated haemoglobin (HbA1), and glucose tolerance values was significantly improved during metformin treatment, while plasma insulin concentrations were not altered. These results indicate that metformin produces a rapid and protracted increase in low affinity insulin receptors in type II diabetes, associated with greater insulin sensitivity and improved diabetic control.     

Modeling enzyme immobilization in porous solid supports

Enzymes are often immobilized on the internal surfaces of porous solid by immersing enzyme-free particles in a well mixed solution of enzyme. The ensuing impregnation process involves coupled transient mass transfer and surface attachment of enzyme. A mathematical model is employed to explore the influences of process parameters on the amount of enzyme loaded and the distribution of immobilized enzyme within the support particles. Nonuniform loading of the support occurs under some conditions. This is significant since the distribution of enzyme within the support particle influences the overall activity and stability of the immobilized enzyme catalyst. The model developed here may also be used to describe removal of reversibly immobilized enzyme during washing or utilization of the immobilized enzyme catalyst.     

Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity

Functional differentiation in mammary epithelia requires specific hormones and local environmental signals. The latter are provided both by extracellular matrix and by communication with adjacent cells, their action being intricately connected in what appears to be a cascade of events leading to milk production. To distinguish between the influence of basement membrane and that of cell-cell contact in this process, we developed a novel suspension culture assay in which mammary epithelial cells were embedded inside physiological substrata. Single cells, separated from each other, were able to assimilate information from a laminin-rich basement membrane substratum and were induced to express beta-casein. In contrast, a stromal environment of collagen I was not sufficient to induce milk synthesis unless accompanied by cell-cell contact. The expression of milk proteins did not depend on morphological polarity since E-cadherin and alpha 6 integrin were distributed evenly around the surface of single cells. In medium containing 5 microM Ca2+, cell-cell interactions were impaired in small clusters and E-cadherin was not detected at the cell surface, yet many cells were still able to produce beta-casein. Within the basement membrane substratum, signal transfer appeared to be mediated through integrins since a function-blocking anti-integrin antibody severely diminished the ability of suspension-cultured cells to synthesize beta-casein. These results provide evidence for a central role of basement membrane in the induction of tissue-specific gene expression.     

A review of the salt sensitivity of the Australian freshwater biota

In Victoria, Australia, both dryland salinity and salinity in irrigation regions are serious agricultural problems. One option to control the latter is to pump groundwater to maintain it below the surface. However, this leaves a saline wastewater for disposal, probably into local streams or wetlands. This review of the salt sensitivity of the biota of Australian streams and wetlands gives information of interest to those responsible for developing controls on these discharges. The review addresses the lethal and sub-lethal effects of salinity on microbes (mainly bacteria), macrophytes and micro-algae, riparian vegetation, invertebrates, fish, amphibians, reptiles, mammals, and birds. Data suggest that direct adverse biological effects are likely to occur in Australian river, stream and wetland ecosystems if salinity is increased to around 1 000 mg L⁻¹. The review highlights a general lack of data on the sensitivity of freshwater plants and animals to salinity increases.     

Effects of gypsum on the uptake,assimilation and cycling of 15N-labelled ammonium and nitrate-N by perennial ryegrass

Solution culture studies have shown that plant uptake of NH₄ ⁺ and NO₃ ^- can be improved by increasing the concentration of Ca²⁺ in the root environment: the same may be true for grass grown in soil culture. An experiment was set up to see whether gypsum (CaSO₄ 2H₂O) increased the rate at which perennial ryegrass absorbed ¹⁵NH₄ ⁺ and ¹⁵NO₃ ^- from soil.The results demonstrated that gypsum increases the rates of uptake of both NH₄ ⁺ and NO₃ ^- by perennial ryegrass. However because there was little potential for mineral-N loss from the experimental system, either by gaseous emission or by N immobilization, long term improvements in fertilizer efficiency were not observed. Nitrogen cycling from shoots to roots commenced once net uptake of N into plants had ceased. Labelled N transferred thus to roots underwent isotopic exchange with unlabelled soil N. It was suggested that this exchange of N might constitute an energy drain from the plant, if plant organic N was exchanged for soil inorganic N. The fact that the exchange occurred at all cast doubt on the suitability of the ¹⁵N-isotope dilution technique for assessing fertilizer efficiency in medium to long term experiments. There was evidence that the extra NO₃ ^--N taken up by plants on the all-nitrate treatments as a result of gypsum application, was reduced in root tissue rather than in shoots, but to the detriment of subsequent root growth and N uptake.