Biosynthesis of ubiquinone and ubichromenol in vitamin A-deficient rats

1. The concentrations of ubiquinone and ubichromenol increased in the livers, but not in the intestines and kidneys, of rats maintained on a diet deficient in vitamin 2. After short time intervals (e.g. 2 h) following administration of the tracer, incorporation of [2-14C]mevalonate into ubiquinone and ubichromenol in livers of vitamin A-deficient rats was lower than for normal animals; this was in contrast to later times (e.g. 72 h) when it was higher. 3. The “newly synthesized” ubiquinone in livers of vitamin A-deficient rats was distributed in all the cell fractions without specific localization. 4. Absorbed exogenous [14C]ubiquinone and [14C]ubichromenol were retained in the livers of vitamin A-deficient rats to a larger extent and for a longer time than in the normal animals. 5. The results suggest that the accumulation of ubiquinone and ubichromenol in the livers of vitamin A-deficient rats is due to lowered catabolism and not to increased rate of synthesis.

Intracellular concentrations of Ca2+ modulate the strength of signal and alter the outcomes of cytotoxic T-lymphocyte antigen-4 (CD152)-CD80/CD86 interactions in CD4(+) T lymphocytes

The costimulatory receptors CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 and their ligands, CD80 and CD86, are expressed on T lymphocytes; however, their functional roles during T cell-T cell interactions are not well known. The consequences of blocking CTLA-4-CD80/CD86 interactions on purified mouse CD4(+) T cells were studied in the context of the strength of signal (SOS). CD4(+) T cells were activated with phorbol 12-myristate 13-acetate (PMA) and different concentrations of a Ca2+ ionophore, Ionomycin (I), or a sarcoplasmic Ca2+ ATPase inhibitor, Thapsigargin (TG). Increasing concentrations of I or TG increased the amount of interleukin (IL)-2, reflecting the conversion of a low to a high SOS. During activation with PMA and low amounts of I, intracellular concentrations of calcium ([Ca2+](i)) were greatly reduced upon CTLA-4-CD80/CD86 blockade. Further experiments demonstrated that CTLA-4-CD80/CD86 interactions reduced cell cycling upon activation with PMA and high amounts of I or TG (high SOS) but the opposite occurred with PMA and low amounts of I or TG (low SOS). These results were confirmed by surface T-cell receptor (TCR)-CD3 signalling using a low SOS, for example soluble anti-CD3, or a high SOS, for example plate-bound anti-CD3. Also, CTLA-4-CD80/CD86 interactions enhanced the generation of reactive oxygen species (ROS). Studies with catalase revealed that H2O2 was required for IL-2 production and cell cycle progression during activation with a low SOS. However, the high amounts of ROS produced during activation with a high SOS reduced cell cycle progression. Taken together, these results indicate that [Ca2+](i) and ROS play important roles in the modulation of T-cell responses by CTLA-4-CD80/CD86 interactions.

A detailed study of Li-DNA fibres at various salt concentrations reveals a non-helical B-DNA and a possible similarity of solution and solid state structures

A thorough investigation of salt concentration dependence of lithium DNA fibres is made using X-ray diffraction. While for low salt the C-form pattern is obtained, crystalline B-type diffraction patterns result on increasing the salt concentration. The salt content in the gel (from which fibres are drawn) is estimated by equilibrium dialysis using the Donnan equilibrium principle. The salt range giving the best crystalline B pattern is determined. It is found that in this range meridional reflections occur on the fourth and sixth layer lines. In addition, the tenth layer meridian is absent at a particular salt concentration. These results strongly suggest the presence of non-helical features in the DNA molecule. Preliminary analysis of the diffraction patterns indicates a structural variability within the B-form itself. Further, the possibility of the structural parameters of DNA being similar in solid state and in solution is discussed.

Functional changes in rat liver mitochondria on administration of 2-methyl-4-dimethylaminoazobenzene

Administration of 2-methyl-4-dimethylaminobenzene in the diet (0.1%, w/w) for 85-90 days doubled the content of mitochondria in the livers of rats. The azodye was covalently bound to liver proteins, and about 15% of the amount found in liver was associated with the mitochondrial fraction. Mitochondria isolated from the livers of azodye-fed animals showed drastically lowered ability to oxidize NAD+-linked substrates. The inhibited electron-transfer step was the reduction of ubiquinone. The organelles showed a large increase in succinate oxidase activity. The activity of cytochrome oxidase and the content of cytochrome aa3 were substantially higher in these organelles. Azodye-fed animals showed depressed serum cholesterol concentrations. The content of ubiquinone in liver also registered a small increase.

The regulation of the biosynthesis of ubiquinone in the rat

The urinary excretion of p-hydroxybenzoate was not altered by ubiquinone feeding, but, although decreased considerably, was not eliminated in protein deficiency. The incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone in vivo increased in cold-exposed and p-chlorophenoxyisobutyrate (clofibrate)-fed rats, and these changes were parallel with the changes in the incorporation of [2-14C]mevalonate under these conditions. Starvation, cholesterol feeding and cholic acid feeding resulted in the decreased incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, confirming the decreased ubiquinone synthesis. Feeding exogenous ubiquinone increased the hepatic ubiquinone concentration, but did not cause any decrease in the incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, indicating the absence of a feedback control.

Dynamics of Circulating Concentrations of Gonadotropins and Ovarian Hormones Throughout the Menstrual Cycle in the Bonnet Monkey: Role of Inhibin A in the Regulation of Follicle-Stimulating Hormone Secretion

In higher primates, increased circulating follicle-stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P-4)secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern Of P-4 secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3 +/- 2 vs. 27.3 +/- 3 pg/mL), and a 2- to 3-fold rise in circulating FSH levels by 24 hr (0.20 +/- 0.02 vs. 0.53 +/- 0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 mu g/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P-4 concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817-824, 2009.

Review of continuum, finite element and hybrid techniques in the analysis of stress concentrations in structures

When a uniform flow of any nature is interrupted, the readjustment of the flow results in concentrations and rare-factions, so that the peak value of the flow parameter will be higher than that which an elementary computation would suggest. When stress flow in a structure is interrupted, there are stress concentrations. These are generally localized and often large, in relation to the values indicated by simple equilibrium calculations. With the advent of the industrial revolution, dynamic and repeated loading of materials had become commonplace in engine parts and fast moving vehicles of locomotion. This led to serious fatigue failures arising from stress concentrations. Also, many metal forming processes, fabrication techniques and weak-link type safety systems benefit substantially from the intelligent use or avoidance, as appropriate, of stress concentrations. As a result, in the last 80 years, the study and and evaluation of stress concentrations has been a primary objective in the study of solid mechanics. Exact mathematical analysis of stress concentrations in finite bodies presents considerable difficulty for all but a few problems of infinite fields, concentric annuli and the like, treated under the presumption of small deformation, linear elasticity. A whole series of techniques have been developed to deal with different classes of shapes and domains, causes and sources of concentration, material behaviour, phenomenological formulation, etc. These include real and complex functions, conformal mapping, transform techniques, integral equations, finite differences and relaxation, and, more recently, the finite element methods. With the advent of large high speed computers, development of finite element concepts and a good understanding of functional analysis, it is now, in principle, possible to obtain with economy satisfactory solutions to a whole range of concentration problems by intelligently combining theory and computer application. An example is the hybridization of continuum concepts with computer based finite element formulations. This new situation also makes possible a more direct approach to the problem of design which is the primary purpose of most engineering analyses. The trend would appear to be clear: the computer will shape the theory, analysis and design.

Feedback-type inhibition of activity of 3-hydroxy-3-methylglutaryl coenzyme a reductase by ubiquinone

Accompanying the decrease in serum cholesterol and increase in concentration of ubiquinone in liver and its microsomes, the activity, but not the protein, of HMG-CoA reductase decreased in ubiquinone-supplemented rats. A soluble 58-kDa preparation of HMG-CoA reductase was partially inhibited on addition of ubiquinone indicating a possible feedback type of action.

A novel fibre-coated sorbent for rapid removal of heavy metals from wastewater. Sorption of Zinc(II) from dilute aqueous solutions in the presence of high concentrations of common salts

The commercial acrylic fibre "Cashmilon" was partially hydrolyzed to convert a fraction of its nitrile (-CN) groups to carboxylic acid (-COOH) groups and then coated with polyethylenimine (PEI) resin and cross-linked with glutaraldehyde to produce a novel gel-coated fibrous sorbent with multiple functionalities of cationic, anionic and chelating types, and significantly faster sorption kinetics than bead-form sorbents. The sorption properties of the fibrous sorbent were measured using Zn(II) in aqueous solution as the sorbate to determine the effects of pH and the presence of common ions in the solution on the sorption capacity. The rate of sorption on the gel-coated fibre was measured in comparison with that on Amberlite IRA-68 weak-base resin beads, to demonstrate the marked difference between fibre and bead-form sorbents in their kinetic behaviour.

Metabolism of ubiquinone in relation to vitamin a status in the rat

1. 1. Biosynthetic experiments in vitro with slices of livers from normal and vitamin A-deficient rats confirmed that synthesis of ubiquinone did not increase in vitamin A deficiency. 2. 2. During development of deficiency of vitamin A in the rat, there was a definite increase in the synthesis of ubiquinone at the 10-days stage but this reverted to low, initial level by 20 days and after. 3. 3. Vitamin A analogues, 3-dehydroretinal, 5,6-monoepoxyretinal and retinoic acid, which supported growth have restored ubiquinone concentration to the normal levels and relieved the lowering in its catabolism. The biologically inert 5,8-monoepoxyretinal was the least active of the analogues tested. 4. 4. The concentration and synthesis of ubiquinone in the liver decreased under conditions of hypervitaminosis A. 5. 5. The experimental evidence does not support the hypothesis of inverse relationship between vitamin A and ubiquinone synthesis.

Effect of cold exposure on the metabolism of ubiquinone in the rat

1. Accumulation of ubiquinone in the livers of rats exposed to a cold environment was shown to be due to both decreased catabolism during the entire experimental period and increased synthesis during an intermediate stage (10–20 days). 2. The increased endogenous synthesis in the cold-exposed rats was eliminated when ubiquinone accumulated in the liver after exposure for 40 days (coinciding with cclimatization), or by absorption of the exogenous dietary supply, possibly by the mechanism of end-product regulation.

A novel fibre-coated sorbent for rapid removal of heavy metals from wastewater. Sorption of Zinc(II) from dilute aqueous solutions in the presence of high concentrations of common salts

The commercial acrylic fibre "Cashmilon" was partially hydrolyzed to convert a fraction of its nitrile (-CN) groups to carboxylic acid (-COOH) groups and then coated with polyethylenimine (PEI) resin and cross-linked with glutaraldehyde to produce a novel gel-coated fibrous sorbent with multiple functionalities of cationic, anionic and chelating types, and significantly faster sorption kinetics than bead-form sorbents. The sorption properties of the fibrous sorbent were measured using Zn(II) in aqueous solution as the sorbate to determine the effects of pH and the presence of common ions in the solution on the sorption capacity. The rate of sorption on the gel-coated fibre was measured in comparison with that on Amberlite IRA-68 weak-base resin beads, to demonstrate the marked difference between fibre and bead-form sorbents in their kinetic behaviour.

Effect of dietary cholesterol and ubiquinone on isoprene synthesis in rat liver

The effect of dietary cholesterol and ubiquinone on the synthesis of isoprene compounds in the liver, as tested by the incorporation of acetate-1-14C and mevalonate-2-14C, was studied in rats. In cholesterol feeding, there appears to be a second site of inhibition after squalene in addition to the previously known primary site of inhibition at the β-hydroxy-β-methyl glutaryl-CoA reductase. Feeding ubiquinone inhibited at some common step between acetate and mevalonate in the synthesis of both cholesterol and ubiquinone, without affecting the acetate activation or fatty acid synthesis, and also at a step in the synthesis of ubiquinone not common with the synthesis of cholesterol. These results are suggestive of a role for ubiquinone in the regulation of isoprene synthesis.