Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population

The purpose of the present study was to investigate the distribution of PON1 Q192R and L55M polymorphisms and activities in a North African population and to determine their association with cardiovascular complications. The prevalence of the QQ, QR, RR, LL, LM, and MM genotypes in the study population was 55.4%, 34.09%, 9.83%, 41.97%, 48.20%, and 9.83% respectively. The Q, R, L, and M alleles had a gene frequency of 0.755, 0.245, 0.67, and 0.33, respectively. The PON1 192 RR genotype was significantly more prevalent among ACS patients than among healthy subjects. There was a 4.33-fold increase in the risk of ACS in subjects presenting the PON1 192 RR genotype compared to those with the QQ genotype (OR=4.33; 95% CI=1.27–17.7). There was a significantly different distribution of PON1 L55M in the ACS patient groups (UA, STEMI, NSTEMI). Moreover, individuals presenting the PON1 55MM genotype present a higher risk for ACS than those with LL genotype (OR=3.69; 95% CI=1.61–11.80). Paraoxonase activities were significantly lower in coronary patients than in healthy subjects. The decrease in PON1 activity was inversely correlated with the number of concomitant risk factors for CVD (r=0.57, p<0.0001). The results of the present study suggested that the PON1 R and M alleles may play a role in the pathogenesis of cardiac ischemia in our North African population and that a decrease in PON1 activity may be a valuable marker for monitoring the development of the atherosclerosis process and the associated cardiovascular complications.     

Submicroscopic deletions of 17p13.3 in type 1 Lissencephaly

DNA markers YNZ22.1 and YNH37.3 were studied by Southern blotting in 14 patients with typical (11 cases) and atypical (3 cases) type 1 Lissencephaly, all with normal high resolution karyotype. A submicroscopic deletion was found in 2 typical cases: one with Miller-Dieker Syndrome (MDS), the other with Isolated Lissencephaly Sequence (ILS). These results suggest a genetic continuum between MDS and ILS. The low frequency of such deletions, especially in ILS, will necessitate direct testing of the newly identified LIS 1 gene.     

Anatomical and biochemical changes during adventitious rooting of apple rootstocks MM 106 cultured in vitro

Adventitious rooting in microcuttings of Malus rootstocks MM106 was studied as regards their histological and biochemical aspects. Microcuttings from shoots raised in Murashige and Skoog's (1962) medium were transferred into a rooting medium containing IBA in the dark, then fixed 0, 3, 5, 7 and 10 days after. Some cambial zone and adjacent phloem cells became dense cytoplasm, nuclei with prominent nucleoli and the first cell divisions were observed at day 3. Meristemoids became individualized, consisting of densely staining cells (with enlarged nucleoli) formed outside the xylem by day 5. Identifiable root primordia with a conical shape and several cell layers were present at day 7. Roots with organized tissue system emerged from the stem 10 days after the root induction treatment. From these histological observations, it can be established that the rooting induction stage ended before day 3. The initiation stage, with the first histological modifications to the formation of meristemoids, would correspond to the transient increase of our biochemical marker (peroxidase activity) until day 5. The best rooting percentage obtained with cultures in the presence of auxin during 5 days confirms this hypothesis. The expression of rooting can then take place.     

Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis

The Mus81-Eme1 endonuclease is implicated in the efficient rescue of broken replication forks in Saccharomyces cerevisiae and Schizosaccharomyces pombe. We have used gene targeting to study the function of the Mus81-Eme1 endonuclease in mammalian cells. Mus81-deficient mice develop normally and are fertile. Surprisingly, embryonic fibroblasts from Mus81(-/-) animals fail to proliferate in vitro. This proliferation defect can be rescued by expression of the papillomavirus E6 protein that promotes degradation of p53. When grown in culture, Mus81(-/-) cells have elevated levels of DNA damage, acquire chromosomal aberrations, and are hypersensitive to agents that generate DNA cross-links. In contrast to the situation in yeast, murine Mus81 is not required for replication restart following camptothecin treatment. Mus81(-/-) mice and cells are hypersensitive to DNA cross-linking agents. Cross-link-induced double-strand break formation is normal in Mus81(-/-) cells, but the resolution of repair intermediates is not. The persistence of Rad51 foci in Mus81(-/-) cells suggests that Mus81 acts at a late step in the repair of cross-link-induced lesions. Despite these defects, Mus81(-/-) mice do not show increased predisposition to lymphoma or any other malignancy in the first year of life.     

Effect of salt stress on growth, fatty acids and essential oils in safflower (Carthamus tinctorius L.)

This study examined the influence of salt treatment on the growth parameters (fresh and dry weights), the mineral content (K⁺ and Na⁺), total lipid contents, fatty acid composition, yields and chemical composition of the essential oil of safflower (Carthamus tinctorius L.) grown in hydroponics for 2 weeks. Results showed that the application of 50 mM NaCl reduced the fresh weight of aerial parts (shoots and leaves) while it enhanced those of the roots. The reduction of dry weight was found to be more pronounced in the aerial parts. Salt treatment increased markedly the concentrations of Na⁺ in both plant parts while it reduced those of K⁺ which resulted in a sharp reduction of K⁺/Na⁺ ratio. In response to salt treatment, total lipids contents decreased in both plant parts and great qualitative changes in the fatty acids profiles were observed. Whatever the plant parts analysed, a redirection of the lipidic metabolism towards synthesis of unsaturated fatty acids as revealed by the increase of double bond index and linoleic desaturation ratio was pointed out. The increased unsaturation index was found to be more important in roots than in aerial parts. Such treatment also reduced the essential oil yields and induced marked quantitative changes in the chemical composition of the essential oils from both plant parts. Of all the identified components, oxygenated components display a prominent salt-induced synthesis and/or accumulation in both roots and aerial parts.     

Fibroblasts from long‐lived species of mammals and birds show delayed,but prolonged,phosphorylation of ERK

Fibroblasts from long‐lived mutant mice show diminished phosphorylation of the stress‐activated protein kinases ERK1/2 after exposure to peroxide, cadmium, or paraquat. We have now evaluated the kinetics of ERK phosphorylation in fibroblasts from long‐lived and short‐lived species of mammals and birds in response to stress by cadmium or hydrogen peroxide. Fibroblasts from the shorter‐lived species of rodents and birds showed rapid induction of ERK phosphorylation, with a decline to basal level within 60 min. In contrast, cells from longer‐lived species showed slower and more prolonged activation of ERK phosphorylation. These results suggest that fibroblasts from long‐lived species may be less susceptible to the early phases of damage from cadmium or peroxide and suggest that altered kinetics of ERK activity may contribute to their stress resistance properties.     

Population structure of Tunisian Leishmania infantum and evidence for the existence of hybrids and gene flow between genetically different populations

Twenty-seven strains of Leishmania infantum from north and central Tunisia belonging to the three main MON zymodemes (the MON-typing system is based on multilocus enzyme electrophoresis (MLEE) of 15 enzymes) found in this country (MON-1, MON-24 and MON-80) and representing different pathologies (visceral, cutaneous and canine leishmaniasis) have been studied to understand the genetic polymorphism within this species. Intraspecific variation could be detected in L. infantum by the use of 14 hypervariable microsatellite markers. In addition to microsatellite repeat length variation, a high degree of allelic heterozygosity has been observed among the strains investigated, suggestive of sexual recombination within L. infantum groups. The two major clusters found by using Bayesian statistics as well as distance analysis are consistent with the classification based on isoenzymes, dividing Tunisian L. infantum into MON-1 and MON-24/MON-80. Moreover, the existence of hybrid strains between the MON-1 and the non-MON-1 populations has been shown and verified by analysis of clones of one of these strains. Substructure analysis discriminated four groups of L. infantum. The major MON-1 cluster split into two groups, one comprising only Tunisian strains and the second both Tunisian and European strains. The major MON-24 cluster was subdivided into two groups with geographical and clinical feature correlations: a dermotropic group of strains mainly from the north, and a viscerotropic group of strains from the centre of Tunisia. The four viscerotropic hybrid strains all originated from central Tunisia and were typed by MLEE as MON-24 or MON-80. To our knowledge, this is the first report describing relationships between clinical picture and population substructure of L. infantum MON-24 based on genotype data, as well as the existence of hybrids between zymodemes MON-1 and MON-24/MON-80, and proving one of these hybrid strains by molecular analysis of the parent strain and its clones.     

Physiological and antioxidant responses of <Emphasis Type="Italic">Mentha pulegium</Emphasis> (Pennyroyal) to salt stress

Mentha pulegium L. is a medicinal and aromatic plant belonging to the Labiatae family present in the humid to the arid bioclimatic regions of Tunisia. We studied the effect of different salt concentrations on plant growth, mineral composition and antioxidant responses. Physiological and biochemical parameters were assessed in the plant organs after 2 weeks of salt treatment with 25, 50, 75 and 100 mM NaCl. Results showed that, growth was reduced even by 25 mM, and salt effect was more pronounced in shoots (leaves and stems) than in roots. This growth decrease was accompanied by a restriction in tissue hydration and K⁺ uptake, as well as an increase in Na⁺ levels in all organs. Considering the response of antioxidant enzymes to salt, leaves and roots reacted differently to saline conditions. Leaf and root guaiacol peroxidase activity showed an increase by different concentration of NaCl, but superoxide dismutase activity in the same organs showed a slight modification in NaCl-treated leaves and roots. Moreover, polyphenol contents and antioxidant activity were analysed in M. pulegium leaves and roots under salt constraint. The analysis showed an increase of total polyphenol content (2.41–8.17 mg gallic acid equivalent g⁻¹ dry weight) in leaves. However, methanol extract of leaves at 100 mM NaCl displayed the highest DPPH· scavenging ability with the lowest IC₅₀ value (0.27 μg ml⁻¹) in comparison with control which exhibited IC₅₀ equal to 0.79 μg ml⁻¹.     

Distribution of phenolic compounds and antioxidant activity between young and old leaves of Carthamus tinctorius L. and their induction by salt stress

In the present work, we investigated the effect of salt stress on the distribution of safflower (Carthamus tinctorius L.) antioxidant system in relation to leaf age. The study was carried out under growth chamber conditions using seedlings of three cultivars which were subjected to 0 and 50 mM NaCl for 3 weeks. Leaf growth, water content, lipid peroxidation, and phenolic compound (total polyphenols, total flavonoids, and proanthocyanidins) concentration were measured at two leaf stages (young and old leaves). Leaf growth was affected by salinity only in Kairouan cultivar that also showed a significant decrease in old leaf water content. By contrast, Gabes and Tazarka cultivars maintained their old leaf water content constant and showed a reduction in that of young leaves. This could be attributed to a higher aptitude of the latter two cultivars to use absorbed sodium and chloride for osmotic adjustment in old leaves, keeping potassium for specific functions. Salt-induced lipid peroxidation was observed only in old leaves, whereas the accumulation of the major phenolic compounds under saline conditions was higher in young leaves, except in Gabes cultivar where no significant difference was found between the two leaf stages. A significant variability was also found between the three cultivars. The better behavior of salt-challenged leaves of Gabes and Tazarka cultivars compared to that of Kairouan cultivar may be related to their higher water content and the accumulation of polyphenols, in particular flavonoids that were shown to be efficiently involved in the restriction of salt-induced oxidative damages.