Effect of pH,mono- and divalent cations on the mixing of phosphatidylglycerol with phosphatidylcholine. A monolayer (π, ΔV) and fluorescence study

The mixing of various molecular species of phosphatidylglycerol and phosphatidylcholine differing in their acyl chain lengths has been studied both in monolayers (π, Δ$\text{V}$), and in water dispersions (fluorescence polarization) with varying pH and ionic strength of the aqueous phase and in the presence of the divalent cations Mg²⁺ and Ca²⁺. In dilauroylphosphatidylglycerol/dipalmitoylphosphatidylcholine mixtures, both in monolayers and in water dispersions, no phase separation was detected at pH 2.9 where phosphatidylglycerol was protonated. With dipalmitoylphosphatidylglycerol/dipalmitoylphosphatidylcholine mixtures, in monolayers and at the same pH, no phase separation was detected for surface pressures below $\text{π = 40}\text{mN}\text{·}\text{m}{}^{\mathrm{?1}}$. In monolayers, and under ionic conditions such that phosphatidylglycerol was ionized (pH 5.6, 10 mM NaCl) miscibility was observed with dilauroylphosphatidylglycerol and dipalmitoylphosphatidylcholine and also with dipalmitoylphosphatidylglycerol and dilauroylphosphatidylcholine. Varying the ionic strength did not alter the miscibility of these lipids. The divalent cations Mg²⁺ and Ca²⁺ did not modify that of dilauroylphosphatidylglycerol with dilauroylphosphatidylcholine or with dipalmitoylphosphatidylcholine. Both in monolayers and in water dispersions, dipalmitoylphosphatidylglycerol and dilauroylphosphatidylcholine appeared to be at least partly miscible, in the presence of magnesium. Only in the presence of calcium and at high surface pressure might the monolayer data account for phase separation between these two lipids. The data presented demonstrate the existence of strong cohesive forces between phosphatidylcholine and phosphatidylglycerol with a marked influence of the former on the physical state of the latter. From an analysis of the Δ$\text{V}$ data, it is suggested that intrafacial hydrogen bonds may play a significant role in stabilizing phosphatidylcholine/phosphatidylglycerol mixtures.     

Mycobacteria glycolipids as potential pathogenicity effectors: alteration of model and natural membranes

Four mycobacterial wall glycolipids were tested for their effects on phospholipidic liposome organization and passive permeability and on oxidative phosphorylation of isolated mitochondria. From fluorescence polarization of diphenylhexatriene performed on liposomes it was concluded that the two trehalose derivatives (dimycoloyltrehalose and polyphthienoyltrehalose) rigidified the fluid state of liposomes, the triglycosyl phenolphthiocerol slightly fluidized the gel state, while the peptidoglycolipid ("apolar" mycoside C) just shifted the phase transition temperature upward. Dimycoloyltrehalose was without effect on liposome passive permeability, as estimated from dicarboxyfluorescein leak rates, and polyphthienoyltrehalose and triglycosyl phenolphthiocerol slightly decreased leaks, while mycoside C dramatically increased leaks. Activity of these lipids on mitochondrial oxidative phosphorylation was examined. The two trehalose derivatives have been tested previously: both had the same type of inhibitory activity, dimycoloyltrehalose being the most active. Triglycosyl phenolphthiocerol was inactive. Mycoside C was very active, with effects resembling those of classical uncouplers: this suggested that its activity on mitochondria was related to its effect on permeability. All these membrane alterations were called nonspecific because it is likely that they result from nonspecific lipid-lipid interactions, and not from recognition between specific molecular structures. Such nonspecific interactions could be at the origin of some of the effects of mycobacteria glycolipids on cells of the immune system observed in the last few years.     

Exploring the active site of Trypanosoma brucei phosphofructokinase by inhibition studies: specific irreversible inhibition

This work deals with the phosphofructokinase enzyme (PFK) of the parasite Trypanosoma brucei. Inhibitors which are analogues of fructose-6-phosphate (F6P) derived from 2,5-anhydromannitol and therefore blocked in a closed conformation, both nonphosphorylated and phosphorylated, were designed. They provided information on this class of ATP-dependent PFK (structurally more similar to PPi-dependent PFKs revealing (i) an ordered mechanism, ATP binding first, inducing an essential conformational change to increase the affinity for F6P, and (ii) a rather hydrophobic environment at the ATP binding site. Nonphosphorylated mannitol derivatives bind at both the ATP and F6P binding sites, whereas the phosphorylated derivatives only bind at the ATP binding site. The inhibitors bearing an aromatic ring substituted at the meta position indicate a polar interaction with lysine 227, which is specific to T. brucei PFK and is replaced by a glycine in human PFK. This lysine can be irreversibly bound, leading to inhibition when an electrophilic carbon atom is beta to the meta position on the ring. This lysine was identified by site-directed mutagenesis. This first example of a specific irreversible inactivation of T. brucei PFK offers an opportunity to develop biologically active compounds against the sleeping sickness, the causative agent of which is the trypanosome.     

Whole Blood Selenium Levels in Healthy Adults from the West of Algeria

The purpose of this study was to assess whole blood selenium levels of 300 healthy adults living in four selected areas of the west of Algeria. Selenium was measured using differential pulse cathodic stripping voltammetry with a detection limit of 29.20 μg/L. The mean of whole blood selenium concentrations was 85.65 ± 21.60 μg/L ranging between 30.90 and 144.04 μg/L. This concentration did not vary significantly (P > 0.05) in relation to the gender of the subject, with concentrations of 87.75 ± 21.30 μg/L in men and 83.95 ± 21.60 μg/L in women group. Individuals older than 60 years had a whole blood selenium concentration significantly lower than the rest of the population. However, the measured selenium concentrations in the residential areas were not statistically different (P > 0.05). A total of 32 (10.70%) individuals exhibited whole blood selenium level below 60 μg/L. These results are similar to those of some European countries but are much lower than data observed in USA or seleniferous regions.     

How do the suprachiasmatic nuclei of the hypothalamus integrate photoperiodic information?

The suprachiasmatic nucleus of the hypothalamus (SCN) plays an essential role in the generation and maintenance of circadian rhythms in mammals. The SCN activity is also dependent upon the photoperiod. The duration of the SCN sensitive phase to light, in term of Fos induction, is variable and tied to the length of the night. The question is how and by which pathways can photoperiod influence SCN? It is possible following the theoretical model of evening and morning component of the clock that the SCN build itself the photoperiodic signal. That the SCN integrate the photoperiodic information through indirect neural or neuroendocrine pathways is also to consider. Data in favor of these different interpretations are presented.     

Postnatal changes in testicular development and androgen receptors immunolocalization in D'Man ram lambs

The purpose of this study was to characterize testicular development in D'Man ram lambs, focusing primarily on androgen receptors (ARs) immunolocalization in the adenohypophysis and testis that is not still known in the D'Man ram lamb. Lambs (n = 12) were divided into four groups (three lambs per group). Adenohypophysis and testis were fixed and paraffin embedded; cross-section (3 μm) were stained and evaluated with immunohistochemistry. Testis weight increased at a greater rate between two and five months after birth, which was associated with remarkable changes in testicular histology, including significant increases in the diameter of seminiferous tubules. Spermatogenesis started between three and five months after birth; lumen and elongated spermatids were observed for the first time in three and four months-old animals respectively. ARs detected with immunohistochemistry were located in the nuclei and cytoplasm of adenohypophysis cells, and only in nuclei of testis cells (Leydig, Sertoli, peritubular myoid and germ cells).