Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.     

Is an intermediate state populated on the folding pathway of ubiquitin?

In the last couple of years, there has been increasing debate as to the presence and role of intermediate states on the folding pathways of several small proteins, including the 76-residue protein ubiquitin. Here, we present detailed kinetic studies to establish whether an intermediate state is ever populated during the folding of this protein. We show that the differences observed in previous studies are attributable to the transient aggregation of the protein during folding. Using a highly soluble construct of ubiquitin, which does not aggregate during folding, we establish the conditions in which an intermediate state is sufficiently stable to be observed by kinetic measurements.     

Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood?

We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation.     

Is beauty in the eye of the beholder?

Theories of beauty were evaluated by requiring subjects to “evolve” a beautiful female face using a Genetic Algorithm. In this procedure, a computer program generated a small population of faces (first generation of phenotypes) from a set of random binary strings (genotypes). Genotypes specified the shapes and soft tissue anthropometrics of facial features. Each of the first generation of faces was rated by a subject (relative fitness measure) for beauty. The fittest genotypes then bred in proportion to their fitness, with crossover and mutation of the binary strings, to produce offspring which were again rated by the subject. This process continued until the most beautiful face, for that subject, was evolved. Forty Caucasian subjects (20 M, 20 F) were required to evolve their idealized beautiful female face using this procedure. The features and soft tissue anthropometrics of their final composites were compared to population norms. Also, the final composites, and different faces generated from the same data base, were rated for beauty by independent judges. The results support the conclusion that the concept of facial beauty is the result of sexual selection, and a beautiful female face has features and proportions indicative on high fertility.     

Platinum(II) diphosphine complexes as catalysts for the Baeyer-Villiger oxidation of ketones: Is it possible to increase the concentration of the active species?

The synthesis and characterization of new bis-aquo platinum(II) complexes of the type [Pt(H₂O)(P-P)][OTf]₂ (OTf = triflate anion), in which the diphosphine P-P is a series of 1,n-bis-diphenyphosphinoalkanes (1a-d, with n = 1-4), 1,2-bis-(di-n-fluorophenylphosphino)ethanes (2a-c, with n = 2, 4-5) and 1,2-bis-dialkylphosphinoethanes (3a-e), where the alkyl substituents at phosphorus have been systematically changed (dmpe) (3a), (depe) (3b), (dippe) (3c), (dcype) (3d) are reported. These complexes were used as catalysts in the Baeyer-Villiger oxidation of 2-methylcyclohexanone, 2-methylcyclopentanone and cyclobutanone with 35% hydrogen peroxide as an environmentally friendly oxidant. The reactions were performed at 25 °C in a chlorinated solvent/H₂O two-phase system. All the investigated catalysts performed better than the corresponding dimeric complexes of general formula [Pt(μ-OH)(P-P)]₂[BF₄]₂ as a consequence of the positive effect imparted by the triflate counter-anion on catalysts speciation.     

Is neurotensin in the brain involved in thermoregulation of the monkey?

Cannulae for intracerebroventricular (ICV) infusion were implanted stereotaxically in monkeys (Macaca fasicularis) maintained post-operatively in a primate restraint chair. During each experiment, a series of physiological measures was recorded simultaneously on a polygraph which included colonic temperature, vasomotor tone, heart rate, respiratory rate, and basal metabolism as reflected by O₂ uptake. The ICV infusion in a volume of 0.5 ml of neurotensin (NT) in doses ranging from 3–150 μg produced neither a statistically significant nor consistent change in body temperature or vasomotor response. Although the highest dose of 450 μg NT infused ICV caused an immediate bradycardia and a concomitant decline in metabolic and respiratory rates, an average decline in core temperature of 0.6°C and the accompanying cutaneous vasodilation often had a latency as long as 1.0 hr. In contrast to the typical hypothermia in this species following an ICV infusion of catecholamines, implicated in the central pathways underlying thermoregulation, NT failed to elicit a coordinated set of physiological responses for heat dissipation in the monkey. Therefore, it is unlikely that this tridecapeptide plays a role in the central mechanisms mediating the control of body temperature of this primate species.     

Co-oxidations of 1,3-diphenylisobenzofuran by the Haber-Weiss reaction. Is singlet oxygen concerned in this oxidation?

The reaction of $\text{O}{}_2{}^{\mathrm{??}}$ with H₂O₂ in the presence of 1,3-diphenylisobenzofuran was studied. o-Dibenzoylbenzene was obtained in 82 % yield, which decreased to 52 % when dimethoxyethane was presence. Additions of β-carotene or 1,4-diazabicyclo-[2,2,2]-octane also inhibited the production of o-dibenzoylbenezene. These results show that singlet oxygen may be a considerable species generated by the Haber-Weiss reaction.     

Is the origin of type 1 diabetes in the gut?

In type 1 diabetes, insulin-producing beta-cells in the pancreas are destroyed by immune-mediated mechanisms. The manifestation of the disease is preceded by the so-called pre-diabetic period that may last several years and is characterized by the appearance of circulating autoantibodies against beta-cell antigens. The role of the gut as a regulator of type 1 diabetes was suggested in animal studies, in which changes affecting the gut immune system modulated the incidence of diabetes. Dietary interventions, alterations in the intestinal microbiota and exposure to enteric pathogens, regulate the development of autoimmune diabetes in animal models. It has been demonstrated that these modulations affect the gut barrier mechanisms and intestinal immunity. Because the pancreas and the gut belong to the same intestinal immune system, the link between autoimmune diabetes and the gut is not unexpected. The gut hypothesis in the development of type 1 diabetes is also supported by the observations made in human type 1 diabetes. Early diet could modulate the development of beta-cell autoimmunity; weaning to hydrolysed casein formula decreased the risk of beta-cell autoimmunity by age 10 in the infants at genetic risk. Increased gut permeability, intestinal inflammation with impaired regulatory mechanisms and dysregulated oral tolerance have been observed in children with type 1 diabetes. The factors that contribute to these intestinal alterations are not known, but interest is focused on the microbial stimuli and function of innate immunity. It is likely that our microbial environment does not support the healthy maturation of the gut and tolerance in the gut, and this leads to the increasing type 1 diabetes as well as other immune-mediated diseases regulated by intestinal immune system. Thus, the interventions, aiming to prevent or treat type 1 diabetes in humans, should be targeting the gut immune system.     

Is there a representative wavelength for photosynthetically active radiation in the terrestrial environment?

Abstract The spectral quality of photosynthetically active radiation (PAR; 400–700 nm) incident at an open site and on a forest floor was analysed to determine whether narrowband (1 nm) wavelengths could be used to estimate total incident PAR. The narrowband estimates were not as good as the broadband estimates based on silicon photovoltaic sensors, but the variance at 530 nm was sufficiently small for narrowband sensors to be considered as low‐cost and light‐weight alternatives to broadband sensors.     

Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Is haemoglobin a biological Fenton reagent?

The ability of oxyhaemoglobin and methaemoglobin to generate hydroxyl radicals (OH.) from H2O2 has been investigated using deoxyribose and phenylalanine as 'detector molecules' for OH.. An excess of H2O2 degrades methaemoglobin, releasing iron ions that react with H2O2 to form a species that appears to be OH.. Oxyhaemoglobin reacts with low concentrations of H2O2 to form a 'reactive species' that degrades deoxyribose but does not hydroxylate phenylalanine. This 'reactive species' is less amenable to scavenging by certain scavengers (salicylate, phenylalanine, arginine) than is OH., but it appears more reactive than OH. is to others (Hepes, urea). The ability of haemoglobin to generate not only this 'reactive species', but also OH. in the presence of H2O2 may account for the damaging effects of free haemoglobin in the brain, the eye, and at sites of inflammation.     

Protein-enhanced decarboxylation of the covalent intermediate in benzoylformate decarboxylase--Desolvation or acid catalysis?

Benzoylformate decarboxylase (BFD) enhances the rate of decarboxylation of its key intermediate compared to the nonenzymic reaction by a factor of about 10⁶. It has been proposed that desolvation into a hydrophobic environment will lower the reaction barrier in TDP-dependent decarboxylases. The competition of thiamin thiazolone diphosphate (TTDP) with the cofactor thiamin diphosphate (TDP) provides a dynamic indication of the relative hydrophobicity of the cofactor binding site. BFD binds the more polar TDP tightly in the presence of excess TTDP. Therefore, desolvation would not be likely to occur during catalysis. Unlike TDP enzymes that have electron acceptors as substrates, decarboxylases require protonation to produce the precursor to the aldehyde product. A mechanism involving an associated acid that traps the carbanion generated upon C–C bond breaking will permit diffusional separation of carbon dioxide and generate the appropriate precursor to the product aldehdye. This would also account for avoidance of a competitive reaction. Hasson’s detailed structure of BFD shows a highly polar active site with histidines in the vicinity of the substrate. Reports of a reduction of k_cat to near the nonenzymic rate without a large effect on K_m upon specific replacement of these histidines with alanine fit this alternative. In TDP enzymes involving oxidation or condensation, an electrophilic substrate or second cofactor will be bound (and no proton will be required). This will acquire the electron density of the carbanion itself. In such cases, protonated side chains are not functional while hydrophobic environments would promote the internal transfer.     

Is GABA Involved in the Development of Caffeine Tolerance?

Caffeine (10 or 20 mg/kg per day, po)-induced stimulation of locomotor activity (LA) reached its peak following 4 consecutive days of caffeine administration. Caffeine-induced stimulation of LA was restored to the control values following caffeine tolerance after 16 or 12 consecutive days of caffeine treatment at a dose of 10 or 20 mg/kg per day, po. Biochemical studies showed that caffeine in the nontolerant condition reduced GABAergic activity in cerebral cortex, corpus striaturn, cerebellum, hypothalamus and pons-medulla; but tolerance to caffeine (10 or 20 mg/kg per day, po) pushed up the GABAergic activity to the control value in all these regions of brain. Further, it was found that muscimol reduced the LA while bicuculline stimulated LA in the caffeine tolerant condition. Thus, from the present study it may be concluded that: (a) caffeine-induced stimulation of LA is dependent on dose and duration of caffeine treatment, (b) development of tolerance to caffeine is dependent on the dosage of caffeine, and (c) the reduction of central GABAergic activity in the caffeine-nontolerant condition pushed up and restored the LA to the control level on the development of tolerance to caffeine.     

Is PsbS the site of non-photochemical quenching in photosynthesis?

The PsbS protein of photosystem II functions in the regulation of photosynthetic light harvesting. Along with a low thylakoid lumen pH and the presence of de-epoxidized xanthophylls, PsbS is necessary for photoprotective thermal dissipation (qE) of excess absorbed light energy in plants, measured as non-photochemical quenching of chlorophyll fluorescence. What is known about PsbS in relation to the hypothesis that this protein is the site of qE is reviewed here.     

Is the impact of environmental noise visible in the dynamics of age-structured populations?

Climate change has ignited lively research into its impact on various population-level processes. The research agenda in ecology says that some of the fluctuations in population size are accountable for by the external noise (e.g. weather) modulating the dynamics of populations. We obeyed the agenda by assuming population growth after a resource-limited Leslie matrix model in an age-structured population. The renewal process was disturbed by superimposing noise on the development of numbers in one or several age groups. We constructed models for iteroparous and semelparous breeders so that, for both categories, the population growth rate was matching. We analysed how the modulated population dynamics correlates with the noise signal with different time-lags. No significant correlations were observed for semelparous breeders, whereas for iteroparous breeders high correlations were frequently observed with time-lags of 71 year or longer. However, the latter occurs under red-coloured noise and for low growth rates when the disturbance is on the youngest age group only. It is laborious to find any clear signs of the (red) noise- and age group-specific fluctuations if the disturbance influences older age groups only. These results cast doubts on the possibility of detecting the signature of external disturbance after it has modulated temporal fluctuations in age-structured populations.