Les blasons de Lascaux

Between 1952 and 1963, the Abbé Glory conducted excavation in the Lascaux Cave. He discovered many artefacts useful for the Prehistoric painter. Today this material is kept in the “Institut de Paléontologie Humaine” in Paris. Some of this material, as well as the painting matter of the “Blazons” of the Black Cow Panel of the Nef, were examined and analysed by electron microscopy: SEM and TEM. Yellow, ocher and red pigments are iron oxides and black pigments are manganese oxides. The results indicate that the pigments were by no means heated, nor associated with any extender. Nevertheless the variety of the raw matter indicates a real strategy to exploit nature in order to match the desired hue and the texture of the painted panel.     

EGF and K+ channel activity control normal and cystic fibrosis bronchial epithelia repair

Severe lesions of airway epithelia are observed in cystic fibrosis (CF) patients. The regulatory mechanisms of cell migration and proliferation processes, involved in the repair of injured epithelia, then need to be better understood. A model of mechanical wounding of non-CF (NuLi) and CF (CuFi) bronchial monolayers was employed to study the repair mechanisms. We first observed that wound repair, under paracrine and autocrine EGF control, was slower (up to 33%) in CuFi than in NuLi. Furthermore, EGF receptor (EGFR) activation, following wounding, was lower in CuFi than in NuLi monolayers. Cell proliferation and migration assays indicated a similar rate of proliferation in both cell lines but with reduced (by 25%) CuFi cell migration. In addition, cell migration experiments performed in the presence of conditioned medium, collected from NuLi and CuFi wounded bronchial monolayers, suggested a defect in EGF/EGFR signaling in CF cells. We (49) recently demonstrated coupling between the EGF response and K(+) channel function, which is crucial for EGF-stimulated alveolar repair. In CuFi cells, lower EGF/EGFR signaling was accompanied by a 40-70% reduction in K(+) currents and KvLQT1, ATP-sensitive potassium (K(ATP)), and Ca(2+)-activated K(+) (KCa3.1) channel expression. In addition, EGF-stimulated bronchial wound healing, cell migration, and proliferation were severely decreased by K(+) channel inhibitors. Finally, acute CFTR inhibition failed to reduce wound healing, EGF secretion, and K(+) channel expression in NuLi. In summary, the delay in CuFi wound healing could be due to diminished EGFR signaling coupled with lower K(+) channel function, which play a crucial role in bronchial repair.     

Centrosome overduplication and mitotic instability in PKD2 transgenic lines

Polycystin-2 (PC-2), a protein encoded by PKD2 and involved in autosomal dominant polycystic kidney disease (ADPKD), is a non-selective cationic channel recently implicated in the function of primary cilia. We recently constructed a new animal model in the form of a transgenic mouse with a BAC-containing human PKD2 inserted in its genome. Two transgenic mouse lines overexpressing human PKD2 showed mitotic instability. Fibroblasts from these transgenic mouse lines have abnormal chromosomal numbers. These lines also have supernumerary centrosomes. PC-2 overexpression is associated with mitotic instability and centrosome overduplication. PC-2 therefore seems to play a role in centrosome duplication, and this hypothesis is being evaluated in other models.     

Post-ovulatory ageing and egg quality: A proteomic analysis of rainbow trout coelomic fluid

Background  

In fish, oocyte post-ovulatory ageing is associated with egg quality decrease. During this period, eggs are held in the body cavity where they bath in a semi-viscous liquid known as coelomic fluid (CF). CF components are suspected to play a role in maintaining oocyte fertility and developmental competence (egg quality). However, CF proteic composition remains poorly studied. Thus rainbow trout CF proteome was studied during the egg quality decrease associated with oocyte post-ovulatory ageing.     

Meiotic weakness: the first division

Cell division is probably the most dramatic event in the life of a cell : the entire genetic material has to be equally distributed into the two daughter cells. Segregation errors have severe consequences and lead to either cell death or the generation of aneuploid cells and may cause the formation of tumors or tumor promoting mutations in somatic cells. In meiosis, they provoke the generation of aneuploid embryos and/or spontaneous abortions. Trisomies in humans, such as trisomy 21, are due to the missegregation of one chromosome in the first meiotic division in the oocyte. This review deals with the molecular mechanisms regulating the two meiotic divisions required for the generation of female haploid germ cells. Here we focus mainly on spindle assembly, and cell cycle regulation especially during the first meiotic division in mouse oocytes (excellent reviews have been written on the peculiar aspects of cell cycle regulation in meiosis II, such as the CSF arrest).     

Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss

Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.     

Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats

Vascular superoxide anion (O(2)(*-)) levels are increased in DOCA-salt hypertensive rats. We hypothesized that the endothelin (ET)-1-induced generation of ROS in the aorta and resistance arteries of DOCA-salt rats originates partly from xanthine oxidase (XO) and mitochondria. Accordingly, we blocked XO and the mitochondrial oxidative phosphorylation chain to investigate their contribution to ROS production in mesenteric resistance arteries and the aorta from DOCA-salt rats. Systolic blood pressure rose in DOCA-salt rats and was reduced after 3 wk by apocynin [NAD(P)H oxidase inhibitor and/or radical scavenger], allopurinol (XO inhibitor), bosentan (ET(A/B) receptor antagonist), BMS-182874 (BMS; ET(A) receptor antagonist), and hydralazine. Plasma uric acid levels in DOCA-salt rats were similar to control unilaterally nephrectomized (UniNx) rats, reduced with allopurinol and bosentan, and increased with BMS. Levels of thiobarbituric acid-reacting substances were increased in DOCA-salt rats versus UniNx rats, and BMS, bosentan, and hydralazine prevented their increase. Dihydroethidium staining showed reduced O(2)(*-) production in mesenteric arteries and the aorta from BMS- and bosentan-treated DOCA-salt rats compared with untreated DOCA-salt rats. Increased O(2)(*-) derived from XO was reduced or prevented by all treatments in mesenteric arteries, whereas bosentan and BMS had no effect on aortas from DOCA-salt rats. O(2)(*-) generation decreased with in situ treatment by tenoyltrifluoroacetone and CCCP, inhibitors of mitochondrial electron transport complexes II and IV, respectively, whereas rotenone (mitochondrial complex I inhibitor) had no effect. Our findings demonstrate the involvement of ET(A) receptor-modulated O(2)(*-) derived from XO and from mitochondrial oxidative enzymes in arteries from DOCA-salt rats.     

Stable low molecular weight RNA profiling showed variations within Sinorhizobium meliloti and Sinorhizobium medicae nodulating different legumes from the alfalfa cross-inoculation group

Four different low molecular weight (LMW) RNA profiles, designated I-IV, among 179 isolates from Medicago, Melilotus and Trigonella species growing in a field site in Northern Spain were identified. From sequence analysis of the 16S rRNA, atpD and recA genes as well as DNA-DNA hybridization analysis with representatives of each LMW RNA profile it was evident that isolates with LMW RNA profiles I and II belonged to Sinorhizobium meliloti and those displaying profiles III and IV to Sinorhizobium medicae. Therefore, two distinct LMW RNA electrophoretic mobility profiles were found within each of these two species. Collectively, LMW RNA profiles I and II (identified as S. meliloti) were predominant in Melilotus alba, Melilotus officinalis and Medicago sativa. Profiles III and IV (identified as S. medicae) were predominant in Melilotus parviflora, Medicago sphaerocarpa, Medicago lupulina and Trigonella foenum-graecum. All the four LMW RNA profiles were identified among isolates from Trigonella monspelliaca nodules. These results revealed a different specificity by the hosts of the alfalfa cross-inoculation group towards the two bacterial species found in this study.     

Lipid profile, fatty acid composition and pro- and anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent behavioral disorder in children and the pathophysiology remains obscure. In addition to the pharmacotherapy, which is the primary treatment of ADHD, nutritional intervention may have a significant impact on ADHD symptoms. We studied lipid and lipoprotein profiles, fatty acid (FA) composition, and oxidant-antioxidant status in 37 pediatric ADHD patients and 35 healthy control subjects. Our results show that plasma triacylglycerols and phospholipids were lower, whereas free cholesterol, HDL, and apolipoprotein A-I were higher in ADHD patients compared with controls. The proportion of plasma EPA and DHA was higher, but that of oleic and alpha-linolenic (ALA) acids was lower. As expected from these findings, the proportions of both total saturates and polyunsaturates fatty acids (PUFA) were higher and lower, respectively, in ADHD patients than in controls, which led to a significant decrease in the PUFAs/saturates ratio. On the other hand, the ratios of eicosatrienoic acid to arachidonic acid and of palmitoleic acid to linoleic acid, established indexes of essential fatty acid (EFA) status remained unchanged revealing that EFA did not affect ADHD patients. Similarly, the activity of delta-6 desaturase, estimated by the ratio of 18:2(n-6)/20:4(n-6), was found unaffected, whereas ALA/EPA was diminished. Lessened lipid peroxidation was noted in ADHD subjects as documented by the diminished values of plasma malondialdehyde accompanied by increased concentrations of gamma-tocopherol. In conclusions, significant changes occur in the lipid and lipoprotein profiles, as well as in the oxidant-antioxidant status of ADHD patients, however, the FA distribution does not reflect n-3 FA deficiency.