QUELQUES CONSIDERATIONS SUR LA RELATION ENTRE DIFFUSION DES TECHNOLOGIES ET RATTRAPAGE

Last years an acceleration of the economic convergence and technological catch-up of developing countries arised, with higher manufactured production growth rates for these countries than for industrialized countries. A wide, although inequal, diffusionDevelopment economics, Economics of innovation, Economics of knowledge, Technological Diffusion, Convergence and catch-up process

Mentoring as a Way of Forming and Effective Utilization of Manpower (the Experience of France)

AbstractThe changing age structure of the population could potentially have significant implications for economic development, labor markets and welfare in countries with different levels of development. In this regard, there are questions related to possible labor shortages and skilled workers, productivity and innovation, as well as the provision of adequate social protection and other services for an aging population. The article analyzes the possibility of using mentoring, engaging experience pensioners considering the high level of education and professional qualifications. There is France experience on the labor force forming and efficient using

Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds

Escherichia coli SOS functions constitute a multifaceted response to DNA damage. We undertook to study the role of yafP, a SOS gene with unknown function. yafP is part of an operon also containing the dinB gene coding for DNA Polymerase IV (PolIV). Our phylogenetic analysis showed that the gene content of this operon is variable but that the dinB and the yafP genes are conserved in the majority of E. coli natural isolates. Therefore, we studied if these proteins are functionally linked. Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV. Similarly, YafP increased cytotoxicity of two DNA damaging nitroaromatic compounds, 4-nitroquinoline-1-oxide (NQO) and nitrofurazone, in the absence of PolIV. The fact that PolIV counterbalances YafP-induced cytotoxicity could explain why these two genes are transcriptionally linked. We also studied the involvement of YafP in genotoxic-stress induced mutagenesis and found that PolIV and YafP reduced NQO-induced mutagenicity. The YafP antimutator activity was independent of the PolIV activity. Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review

Increased placental expression of cannabinoid receptor 1 in preeclampsia

BackgroundThe endocannabinoid system plays a key role in female reproduction, including implantation, decidualization and placentation. In the present study, we aimed to analyze cannabinoid receptor 1 (CB1), CB2 and fatty acid amid hydrolase (FAAH) expressions and localization in normal and preeclamptic placenta, in order to determine whether placental endocannabinoid expression pattern differs between normal pregnancy and preeclampsia.MethodsEighteen preeclamptic patients and 18 normotensive, healthy pregnant women with uncomplicated pregnancies were involved in our case inverted question markcontrol study. We determined CB1, CB2 and FAAH expressions by Western blotting and immunohistochemistry in placental samples collected directly after Cesarean section.ResultsCB1 expression semi-quantified by Western blotting was significantly higher in preeclamptic placenta, and these findings were confirmed by immunohistochemistry. CB1 immunoreactivity was markedly stronger in syncytiotrophoblasts, the mesenchymal core, decidua, villous capillary endothelial and smooth muscle cells, as well as in the amnion in preeclamptic samples compared to normal pregnancies. However, we did not find significant differences between preeclamptic and normal placenta in terms of CB2 and FAAH expressions and immunoreactivity.ConclusionsWe observed markedly higher expression of CB1 protein in preeclamptic placental tissue. Increased CB1 expression might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia. Nevertheless, we did not find significant differences between preeclamptic and normal placental tissue regarding CB2 and FAAH expressions. While the detailed pathogenesis of preeclampsia is still unclear, the endocannabinoid system could play a role in the development of the disease

Localisation and Function of the Endocannabinoid System in the Human Ovary

Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear.Immunohistochemical examination of normal human ovaries indicated that the endocannabinoid system was present and widely expressed in the ovarian medulla and cortex with more intense cannabinoid receptor 2 (CB2) than CB1 immunoreactivity in the granulosa cells of primordial, primary, secondary, tertiary follicles, corpus luteum and corpus albicans. The enzymes, fatty acid amide hydrolase (FAAH) and N-acyclphosphatidylethanolamine-phospholipase D (NAPE-PLD), were only found in growing secondary and tertiary follicles and corpora lutea and albicantes. The follicular fluid (FF) AEA concentrations of 260 FF samples, taken from 37 infertile women undergoing controlled ovarian hyperstimulation for in vitro fertilisation and intracytoplasmic sperm injection with embryo transfer, were correlated with ovarian follicle size (P = 0.03). Significantly higher FF AEA concentrations were also observed in mature follicles (1.43+/-0.04 nM; mean+/-SEM) compared to immature follicles (1.26+/-0.06 nM), P = 0.0142 and from follicles containing morphologically assessed mature oocytes (1.56+/-0.11 nM) compared to that containing immature oocytes (0.99+/-0.09 nM), P = 0.0011. ROC analysis indicated that a FF AEA level of 1.09 nM could discriminate between mature and immature oocytes with 72.2% sensitivity and 77.14% specificity, whilst plasma AEA levels and FF AEA levels on oocyte retrieval day were not significantly different (P = 0.23).These data suggest that AEA is produced in the ovary, is under hormonal control and plays a role in folliculogenesis, preovulatory follicle maturation, oocyte maturity and ovulation

Brain Neuronal CB2 Cannabinoid Receptors in Drug Abuse and Depression: From Mice to Human Subjects

BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R) but not (H316Y) polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis