How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH₂ in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings.     

Adult sex ratio variation: implications for breeding system evolution

Adult sex ratio (ASR) exhibits immense variation in nature, although neither the causes nor the implications of this variation are fully understood. According to theory, the ASR is expected to influence sex roles and breeding systems, as the rarer sex in the population has more potential partners to mate with than the more common sex. Changes in mate choice, mating systems and parental care suggest that the ASR does influence breeding behaviour, although there is a need for more tests, especially experimental ones. In the context of breeding system evolution, the focus is currently on operational sex ratios (OSRs). We argue that the ASR plays a role of similar importance and urge researchers to study the ASR and the OSR side by side. Finally, we plead for a dynamic view of breeding system evolution with feedbacks between mating, parenting, OSR and ASR on both ecological and evolutionary time scales.     

Quantification de l’activité dopaminergique striatale en TEP à la 18F-DOPA : quels paramètres choisir en routine ?

Aim of the studyFunctional assessment of the nigrostriatal dopaminergic pathway (NSDP) is still largely dominated by SPECT imaging of presynaptic dopamine transporters. Because of greater performance characteristics and a potential medico-economic added value, 18F-DOPA PET may advantageously replace SPECT procedures. Clinical analysis of 18F-DOPA PET images is mainly based on visual assessment, a parameter which may be empirically affected by a low reproducibility. We assessed several reproducible semi-quantitative parameters applicable in clinical routine.Material and methodsSeventy-two patients (18 control subjects, 55.2 ± 13.4 years; 54 patients without confirmed Parkinson's disease (no-PD patients): 74.0 ± 9.9 years) were prospectively referred for a 18F-DOPA PET brain study. 18F-DOPA striatal uptake, which reflects the activity level of L-DOPA decarboxylase (DDC), was quantified using calculation methods of SUV in several striatal VOI. Background activity in occipital VOI (non specific uptake) was taken into consideration to assess specific uptake.ResultsDespite the absence of standard of truth regarding the medical status of no-PD patients, the most effective quantitative parameter to assess specific striatal dopaminergic activity was the putamen-to-occipital ratio. According to our data, activity level of DCC might decrease with age.ConclusionAn accurate and early in-vivo detection of NSDP alteration is a critical issue at the earliest stages of PD. Despite limits of this preliminary study, simple semi-quantitative parameters appear to be valuable tools to address problems of classification reproducibility in clinical practice.     

Functionalization of cellulosic fibers by graft copolymerization of acrylonitrile and ethyl acrylate from their binary mixtures

Functionalization of Agave fibers was carried out by graft copolymerization of acrylonitrile (AN) and ethyl acrylate (EA) from their binary solutions in presence of Ce (IV) ions at a temperature of 45 ± 0.1 °C. An increase in the graft copolymerization was obtained with the increase in the feed molarity of the comonomers up to certain extent. Contrary to lesser affinity of acrylonitrile to grafting on Agave fibers, a synergistic effect of ethyl acrylate on acrylonitrile was observed when graft copolymers were prepared using different feed compositions (f_AN). The graft copolymers were characterized by various techniques such as FT-IR, TGA/DTA, X-RD and SEM analysis. Further swelling behavior of grafted fibers in different solvents, moisture absorption behavior and resistance to chemicals was investigated as a function of percent grafting to define their end uses in different environments.     

High sensitivity LC-MS profiling of antibody-drug conjugates with difluoroacetic acid ion pairing

ABSTRACT

Reversed-phase liquid chromatography (RPLC) separations of proteins using optical detection generally use trifluoroacetic acid (TFA) because it is a strong, hydrophobic acid and a very effective ion-pairing agent for minimizing chromatographic secondary interactions. Conversely and in order to avoid ion suppression, analyses entailing mass spectrometry (MS) detection is often performed with a weaker ion-pairing modifier, like formic acid (FA), but resolution quality may be reduced. To gain both the chromatographic advantages of TFA and the enhanced MS sensitivity of FA, we explored the use of an alternative acid, difluoroacetic acid (DFA). This acid modifier is less acidic and less hydrophobic than TFA and is believed to advantageously affect the surface tension of electrospray droplets. Thus, it is possible to increase MS sensitivity threefold by replacing TFA with DFA. Moreover, we have observed DFA ion pairing to concomitantly produce higher chromatographic resolution than FA and even TFA. For this reason, we prepared and used MS-quality DFA in place of FA and TFA in separations involving IdeS digested, reduced NIST mAb and a proprietary antibody-drug conjugate (ADC), aiming to increase sensitivity, resolution and protein recovery. The resulting method using DFA was qualified and applied to two other ADCs and gave heightened sensitivity, resolution and protein recovery versus analyses using TFA. This new method, based on a purified, trace metal free DFA, can potentially become a state-of-the-art liquid chromatography-MS technique for the deep characterization of ADCs.     

Facultative parthenogenesis and sex-ratio evolution

Summary Phenotypic models of selection are used to determine the effect of facultative parthenogenesis on the production of males in a spatially variable environment when (i) sex determination is under strict genetic control, and (ii) when sex may be environmentally determined. The results show that when sex is under strict genetic control and there is some chance of maturing in isolation, selection favors a female-biased sex ratio. When sex can be environmentally induced by cues which indicate high density, selection favors a mixture of genetic and environmental control, such that half the individuals always become female and the other half become females when isolated and become males when not isolated.     

Antiatherogenic effect of a low lysine: arginine ratio of protein involves alteration in the aortic glycosamihoglycans and glycoproteins

The effect of alteration of lysine: arginine ratio of the protein on the aortic glycosaminoglycans and glycoproteins was studied in rats fed cholesterol free and atherogenic diet. The concentration of total glycosaminoglycans and of individual fractions was significantly lower in the aorta in the case of diet with lysine: arginine ratio of 1.0, than the diet with a ratio of 2.0. Rats fed globulin fraction isolated from sesame seeds, which has a lysine: arginine ratio of 0.67 also showed significantly lower concentration of total and individual glycosaminoglycan fractions in the aorta than those fed casein (lysine:arginine ratio 2.0). Concentration of total hexose and fucose in the glycoproteins was also lower in the aorta in the case of lysine: arginine ratio 1.0. These results in the light of previous reports of increase in the aortic glycosaminoglycans in the early stages of atherosclerosis and increase in the total hexose and fucose in the glycoproteins in the atherosclerotic aorta indicate that the antiatherogenic effect of a low lysine: arginine ratio in the protein involves alteration in the aortic glycosaminoglycans and glycoproteins.     

The R453Q and D151A polymorphisms of hexose-6-phosphate dehydrogenase gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity

Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ(2)=3.95, P=0.047), especially within the PCOS subgroup (χ(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; χ(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.     

The effects on operation conditions of sludge retention time and carbon/nitrogen ratio in an intermittently aerated membrane bioreactor (IAMBR)

An intermittently aerated membrane bioreactor (IAMBR) system has been developed to improve the efficiency of nutrient removal, and for the stable treatment of organic matter which is contained as suspended solid (SS) in the influent. The important operating factors of an intermittently aerated bioreactor (IABR) are sludge retention times (SRTs) and carbon/nitrogen (C/N) ratios. Because research on IAMBR is young, this paper explores the effect of SRTs and C/N ratios on these systems. For SRTs of 20, 25, 30, and 40 days, there was little difference in the removal of COD, T–N, and T–P. In comparing C/N ratios of 4.5, 7, and 10, the COD concentration in permeate with a C/N ratio of 10 was most stable, although the concentration of organic matter in the influent was high. The removal efficiencies of T–N and T–P in permeate with a C/N ratio of 10 were the highest at 92.9% and 88.9%, respectively. This implies that a C/N ratio above 10 should be maintained for a nutrient removal efficiency of approximately 90%.