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Because they limit, even reverse, age-induced skin alterations, retinoids became a staple in cosmetology. However, their use can result in undesired secondary effects and there is a demand for natural sources of compounds with retinoid-like effects. A preliminary screening identified a Harungana madagascariensis plant extract (HME) as possibly inducing genes stimulated by retinol. We analysed its effect on gene and protein expression, comparing it to retinoids.Gene expression was analysed by real-time qPCR on RNA from isolated fibroblasts subjected to retinol or the plant extract for 6, 48 or 96 h. Skin markers were quantified in fibroblasts cultured with retinol or extract containing medium, and UV-aged skin explants subjected to topical applications of creams containing retinol, retinaldehyde or HME.Real-time qPCR shows that the extract induced all RARs and RXRs, even RXRγ that was not induced by retinol. Eighty-eight per cent of the 25 early retinoid reaction genes induced by a concentration of retinol are induced by the extract. In fibroblasts, only the extract increased collagen III labelling, while collagen I and fibronectin labelling are increased by retinol and the extract, with higher levels for the extract. When topically applied to UV-aged skin explants, only the cream containing the HME led to increased labelling of CRABP1 in the epidermis. CRABP2 and Ki67 are induced by all three creams and no effect was detected on RXRs. In the dermisthe extract containing cream increased CRABP2, total collagen, procollagen I and collagen I while creams with retinol or retinaldehyde only affected some of these proteins.The HME induces an overall retinol-like gene induction profile in isolated fibroblasts and retinoid-like stimulation of protein synthesis in both isolated fibroblasts and photoaged skin explants.Limitant, voire inversant les altérations cutanées induites par l'âge, les rétinoïdes sont devenus incontournables en cosmétologie. Cependant, leur application topique peut entraîner des effets secondaires indésirables et il existe une demande pour des composés naturels ayant des effets similaires à ceux des rétinoïdes. Un screening préliminaire nous avait permis d'identifier un extrait de la plante Harungana madagascariensis (HME) comme pouvant induire des gènes stimulés par le rétinol. Nous avons donc analysé son effet sur l'expression de gènes et de protéines induits par les rétinoïdes et comparé les résultats à ceux obtenus en présence de rétinoïdes. MÉTHODES: L'expression de gènes a été analysée par qPCR en temps réel réalisée sur l'ARN de fibroblastes isolés soumis au rétinol ou à l'extrait végétal pendant 6, 48 ou 96 heures. Différentes protéines cutanées ont été quantifiés dans des fibroblastes cultivés en présence de rétinol ou d'un milieu contenant l'extrait. Des quantifications ont également été faites sur des explants de peau vieillie par les UV et soumis à des applications topiques de crèmes contenant du rétinol, du rétinaldéhyde ou le HME.La qPCR en temps réel montre que l'extrait induit tous les gènes RARs et RXRs, même RXRγ qui n'était pas induit par le rétinol. Quatre-vingt-huit pour cent des 25 gènes impliqués dans la réaction précoce aux rétinoïdes induits par une concentration de rétinol ont été induits par l'extrait. Dans les fibroblastes, seul l'extrait a augmenté le marquage du collagène III, tandis que le marquage du collagène I et de la fibronectine a été augmenté par le rétinol et l'extrait, avec des niveaux plus élevés pour l'extrait. En application topique sur des explants de peau vieillie par les UV, seule la crème contenant le HME a entraîné une augmentation du marquage de CRABP1 dans l'épiderme. CRABP2 et Ki67 ont été induits par les trois crèmes et aucun effet n'a été détecté sur les RXRs. Dans le derme, la crème contenant l'extrait a augmenté CRABP2, le collagène total, le procollagène I et le collagène I, tandis que les crèmes contenant du rétinol ou du rétinaldéhyde n'ont affecté que certaines de ces protéines.Chez les fibroblastes isolés, le HME induit un profil d'induction génique globalement similaire à celui du rétinol. Chez les fibroblastes isolés et des explants de peau photo-vieillie, il entraine une stimulation de la synthèse protéique similaire à celle des rétinoïdes.

Many aphid species exhibit a variation in reproductive mode which is influenced by winter climate regimes, with cyclical parthenogenetic (CP) lines dominating in cold winter areas (because they produce cold-resistant eggs) and obligate parthenogenetic (OP) ones in mild winter regions (because of their parthenogenetic overwintering). Genetic studies on several aphid species have shown that the OP trait can be transmitted during sexual events involving the 2 types of lines. This genetic system could be considered as a local safeguarding mechanism for OP alleles in case severe frost would have killed all parthenogenetically overwintering individuals. However, this strategy would only be efficient in restoring local polymorphism in breeding systems if the newly hatched OP recombinants remain competitive over their CP counterparts. In this study we compared egg hatching sequences of CP and OP F1 clones from several crosses obtained for 2 cereal aphid species, Sitobion avenae (constant 5 °C, 8 h of light) and Rhopalosiphum padi (winter outdoor conditions). For S. avenae, we obtained F1 offspring from 6 crosses, involving 4 clones while in R. padi F1 were obtained from 11 crosses involving 14 clones. We showed that in both species proportions of OP clones were higher in the first half of the progeny relative to the second half. In addition, F1 OP clones hatched in the mean about a week earlier than their CP sibs, which gives them a demographic advantage at the start of the growth season. We then discussed the consequences of this fitness advantage for the maintenance and spread of the OP trait in aphid populations.

The UK fishing sector has been under the spotlight since the beginning of the Brexit debate. Political commentators claimed that up to 90 per cent of British fishers supported Brexit as they considered the UK was disadvantaged compared to other EU Member States. Their main grudge is about the equal access that all Member States have had to all EU waters – with the exception of territorial waters, up to 12 nautical miles from the coast – since the formal inception of the Common Fisheries Policy (CFP) in 1983. Combined with what they perceive to be an unbalanced allocation of fishing quotas, this legal framework is thought by the UK fishing industry to be the main reason for the poor management of EU fisheries, which could be terminated following Brexit thus regaining the UK's status as an independent coastal state. The key issue addressed in this article is the possible reallocation of fishing opportunities within British waters. It outlines the current allocation system and summarises the views of major stakeholders. This is complex as historical fishing rights may or may not be acknowledged but it remains that the UK fishing industry needs access to EU markets and EU labour to bring the fish to value, Le secteur de la pêche au Royaume‐Uni a été sous les projecteurs depuis le début du débat sur le Brexit. Les commentateurs politiques ont affirmé que jusqu’à 90% des pêcheurs britanniques soutenaient le Brexit car ils considéraient que le Royaume‐Uni était désavantagé par rapport aux autres États membres de l'Union européenne. Leur principale préoccupation concerne l’égalité d'accès de tous les États membres à toutes les eaux de l'Union européenne ‐ à l'exception des eaux territoriales, jusqu’à 12 milles marins de la côte ‐ depuis la création officielle de la Politique commune de la pêche (PCP) en 1983. Ajouté à ce qu'ils perçoivent comme une répartition déséquilibrée des quotas de pêche, ce cadre juridique est considéré par l'industrie de la pêche au Royaume‐Uni comme la principale raison de la mauvaise gestion des pêcheries de l'Union européenne, qui pourrait être supprimée après le Brexit, permettant ainsi au Royaume‐Uni de récupérer son statut d’État côtier indépendant. La question clé abordée dans cet article est la réallocation possible des droits de pêche dans les eaux britanniques. Il décrit le système de répartition actuel et résume les points de vue des principales parties prenantes. Cette question est complexe car les droits de pêche historiques peuvent être reconnus ou non, mais il reste que l'industrie de la pêche britannique a besoin d'accéder aux marchés et aux travailleurs de l'Union européenne pour valoriser le poisson., Der Fischereisektor des Vereinigten Königreichs steht seit Beginn der Brexit‐Debatte im Blickpunkt. Politische Beobachter behaupteten, dass bis zu 90 Prozent der Fischer des Vereinigten Königreichs den Brexit unterstützten, da ihrer Ansicht nach das Vereinigte Königreich im Vergleich zu anderen EU‐Mitgliedstaaten benachteiligt war. Ihr größter Unmut richtet sich gegen den gleichberechtigten Zugang aller Mitgliedstaaten zu allen Gewässern der EU seit der Einführung der Gemeinsamen Fischereipolitik (GFP) im Jahr 1983, mit Ausnahme der Hoheitsgewässer, die bis zu 12 Seemeilen vor der Küste liegen. Dieser Rechtsrahmen zusammen mit einer ihrer Meinung nach unausgewogenen Zuteilung von Fangquoten wird vom Fischereisektor des Vereinigten Königreichs als Hauptgrund für das schlechte Management der EU‐Fischerei angesehen. Das könnte nach dem Brexit beendet werden, wodurch das Vereinigte Königreich seinen Status als unabhängiger Küstenstaat wiedererlangt. Im Mittelpunkt des vorliegenden Beitrags steht die mögliche Neuzuweisung von Fangmöglichkeiten in britischen Gewässern. Es wird das derzeitige Zuteilungssystem skizziert und die Ansichten wichtiger Interessengruppen zusammengefasst. Dies ist durchaus komplex, da historische Fangrechte anerkannt werden können oder auch nicht. Allerdings bleibt es dabei, dass der Fischereisektor des Vereinigten Königreichs Zugang zu den EU‐Märkten und EU‐Arbeitskräften benötigt, um Gewinne zu erzielen.

Alpha-melanocyte stimulating hormone (alpha-MSH) binds to melanocortin-1 receptor (MC1R) on melanocytes to stimulate pigmentation and modulate various cutaneous inflammatory responses. MC1R expression is not restricted to melanocytic cells and may be induced in keratinocytes after UVB exposure. We hypothesized that MC1R signaling in keratinocytes, wherein basal conditions are barely expressed, may modulate mediators of inflammation, such as nuclear factor-kappa B (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha). Therefore, we generated HaCaT cells that stably express human MC1R or the Arg151Cys (R151C) nonfunctional variant. We demonstrate that: (1) the constitutive activity of MC1R results in elevated intracellular cAMP level, reduced NF-kappaB activity and decreased TNF-alpha transcription; (2) binding of alpha-MSH to MC1R and the subsequent increase in cAMP production do not inhibit TNFalpha-mediated NF-kappaB activation; (3) MC1R signaling is sufficient to strongly inhibit UVB-induced TNF-alpha expression and this inhibitory effect is further enhanced by alpha-MSH stimulation. Our findings suggest that the constitutive activity of the G-protein-coupled MC1R in keratinocytes may contribute to the modulation of inflammatory events and immune response induced by UV light.

1 The growth hormone secretagogue receptor 1a (GHSR-1a) is a G-protein coupled receptor, involved in the biological actions of ghrelin by triggering inositol phosphates and calcium intracellular second messengers. It has also been reported that ghrelin could activate the 44- and 42-kDa extracellular signal-regulated protein kinases (ERK1/2) in different cell lines, but it is not clear whether this regulation is GHSR-1a dependent or not. 2 To provide direct evidence for the coupling of GHSR-1a to ERK1/2 activation, this pathway has been studied in a heterologous expression system. 3 Thus, in Chinese hamster ovary (CHO) cells we showed that ghrelin induced, via the human GHSR-1a, a transient and dose-dependent activation of ERK1/2 leading to activation of the transcriptional factor Elk1. 4 We then investigated the precise mechanisms involved in GHSR-1a-mediated ERK1/2 activation using various specific inhibitors and dominant-negative mutants and found that internalization of GHSR-1a was not necessary. Our results also indicate that phospholipase C (PLC) was involved in GHSR-1a-mediated ERK1/2 activation, however, pathways like tyrosine kinases, including Src, and phosphoinositide 3-kinases were not found to be involved. GHSR-1a-mediated ERK1/2 activation was abolished both by a general protein kinase C (PKC) inhibitor, Go6983, and by PKC depletion using overnight pretreatment with phorbol ester. Moreover, the calcium chelator, BAPTA-AM, and the inhibitor of conventional PKCs, Go6976, had no effect on the GHSR-1a-mediated ERK1/2 activation, suggesting the involvement of novel PKC isoforms (ɛ, δ), but not conventional or atypical PKCs. Further analyses suggest that PKCɛ is required for the activation of ERK1/2. 5 Taken together, these data suggest that ghrelin, through GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and PKCɛ-dependent pathway. British Journal of Pharmacology (2006) 148, 350–365. doi:10.1038/sj.bjp.0706727

Preheating induced sensitization has been commonly studied in the frame of SDT but a complete analysis in terms of pyrotechnic safety needs to take into account other kinds of stimuli like “moderate” mechanical ones (crushing, drops…), new thermal fluxes or combined insults. We present the results of connected studies and propose sensitization mechanisms based on these data and on previous chemical and microstructure characterizations.

This paper is devoted to a review of microstructure observations performed on a TATB composition submitted to thermal and combined thermal/mechanical stimuli. Effects are identified and quantified in terms of decomposition extension and microstructure evolution (porosity, shear bands, grains shape and orientation, anisotropy …). Several complex mechanisms and important transformations are exhibited as a function of temperature, heating duration and shock wave intensity. Conclusions on decomposition mechanisms are directly derived from these observations.

We analyze the evolution of the sensitivity of a TATB composition after thermal cycles at elevated temperatures. Sensitization due to thermal cycles is of variable magnitude depending on the kind of the second stimulus (mechanical or thermal). In order to investigate the possible mechanisms which govern these phenomena, we perform an extensive study of the evolution of the chemistry and microstructure of our composition and we determine the sensitivity of our explosive to various stimuli after various temperature/duration cycles. This first paper is devoted to the study of TATB chemical evolutions. We present the results obtained for explosive decomposition, furazan generation, gas analyses and solid residue characterization.

A set of molecular markers to differentiate the aphid (Hemiptera: Aphidoidea) species Sitobion avenae (Fabricius) from Sitobion fragariae (Walker), is presented. These markers correspond to (1) a region of the mitochondrial DNA, (2) five species-specific RAPD banding patterns and (3) four microsatellite loci. Each of the markers was able to clearly distinguish between the species. The utility of each molecular marker is discussed. Mitochondrial DNA is best applicable to species determination and relative abundance, RAPDs to the evaluation of genetic diversity, and microsatellites to the assessment of the population genetic structure: the combined use of mtDNA with the other techniques can be of importance when the presence of hybrids is suspected, and RAPDs with microsatellites are best used together in population genetics and host preference studies.

As French populations of the aphid Sitobion avenae exhibit a range of reproductive modes, this species provides a good opportunity for studying the evolution of breeding system variation. The present analysis combined ecological and genetic investigations into the spatial distribution of variation in reproductive mode. Reproductive mode was characterized in 277 lineages of S. avenae from France, and these aphids were scored for five microsatellite loci. The analyses revealed strong geographical partitioning of breeding systems, with obligate asexuals mostly restricted to the south of France, while lineages producing sexual forms were more common in the north. Contrary to what might be anticipated for organisms with frequent parthenogenesis, there was substantial genic and genotypic diversity, even in the obligately asexual lineages. More than 120 different genotypes were detected among the 277 aphid lineages, with an average of 5.9 alleles per locus (range four to 16) and heterozygosity of 56.7%. As with previous studies of allozyme variation in aphids, most loci showed heterozygote deficits, and disequilibrium was common among allelic variants at different loci, even after removal of replicate copies of genotypes that might have been derived through clonal reproduction. Our results suggest that selection is important in structuring reproductive systems and genetic variation in French S. avenae. Canonical correspondence analysis was employed to examine the associations between genotypic and phenotypic variables, enabling the identification of alleles correlated with life-history traits.

1. Clones of Sitobion avenae from the west of France exhibited four types of responses in growth chambers to short days and low temperatures: in addition to permanently parthenogenetic clones (anholocyclic) and clones producing both males and parthenogenetic females (androcyclic), lineages producing both mating females and males were categorized into holocyclic and intermediate types, the latter investing into both sexual and parthenogenetic reproduction. 2. Holocyclic, intermediate and androcyclic clones were tested outdoors for sexual production in autumn and results were consistent with those obtained in growth chambers. Eggs from holocyclic and intermediate clone selfings were laid and hatched for most crosses. 3. Reciprocal crosses within and between life cycle variants showed no effect of the type of cross on the number of eggs laid per mating female, their hatching success, or the survival and fecundity of the parthenogenetic females born from eggs (fundatrices). 4. Eggs from intermediate × intermediate crosses hatched 20 days earlier than those involving at least one holocyclic parent. It is suggested that this short diapausing time gives a selective advantage to intermediate clones in oceanic climates, which could compensate for their lower sexual production in autumn. 5. Selfed offspring showed inbreeding depression, which seems to be common in non host-alternating aphids. 6. Mating with androcyclic males affects percentage (lower) and time (longer) of egg hatching, but not the other investigated traits. 7. The significance of intragenotypic strategy mixing in androcyclic and intermediate clones is discussed as an overall adaptation to the uncertainty of winter climate in oceanic zones.

2, 6-Dimethyl-8-methoxy-1-lithio-octatetra-1, 3, 5, 7-ene 4 is prepared by bromine-lithium exchange from its readily accessible bromo precursor 8 . The lithio reagent 4 reacts with carbonyl compounds to give in one pot, after a mild acidic hydrolysis, the retinoid aldehydes 2 .