Xenobiotic metabolizing enzymes in the central nervous system: Contribution of cytochrome P450 enzymes in normal and pathological human brain

The metabolism of xenobiotics in human brain constitutes a field of recent intensive research in relation to the potential implications in the pharmacological effect of drugs acting on the central nervous system. Cytochrome P450 enzymes (CYPs) play a crucial role in these metabolic pathways and the existence of functional CYP monooxygenases in brain is now well established. These enzymes are preferentially localized in the neuronal cells within the microsomal fraction and the inner membrane of mitochondria. Although low, the metabolism in situ could influence individual response to xenobiotics or produce reactive, toxic metabolites causing irreversible damage in the neuronal cells. The abundant presence of CYPs in selective cell populations within different regions of the brain has also suggested a role for these enzymes in brain physiology thus not restricted to xenobiotic-induced neurotoxicity. For instance, CYPs participate in the regulation of neurotransmitters and steroids and brain maintenance of cholesterol homeostasis. Recent advances support an additional role for these enzymes in the pathogenesis of psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's and Parkinson's diseases. The characterization of brain CYP isoforms and their localization, the identification of their substrates and metabolic end-products will allow better understanding of the role of these enzymes in brain physiology, development and diseases.     

Behavioural responses of the Colorado potato beetle to trichomes and leaf surface chemicals of Solanum tarijense

Wild Solanum species constitute a source of resistance to several pests and diseases of potato. Several species of wild tuber‐bearing potato have been identified as resistant to the Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), including Solanum tarijense Hawkes (Solanaceae). Our objective was to determine the mechanism of resistance of S. tarijense to the Colorado potato beetle and, because the resistance is limited to the adult stage of the insect, to study the host selection behaviour on resistant plants. In the field, Colorado potato beetles demonstrated a unique behaviour when in contact with S. tarijense, abandoning the plant by falling to the ground after a few minutes. The abundant trichomes on the leaves of S. tarijense induced the falling behaviour. However, on S. tarijense feeding remained low even after the trichomes were mechanically removed. Observations demonstrated that the normal sequence of behaviour leading to feeding was interrupted before adult beetles fed on S. tarijense leaves. Feeding experiments using volatile and non‐volatile fractions of leaf surface extracts identified a phagodeterrent effect of the volatile fraction. Our results contrast with a similar evaluation of the mode of resistance of Solanum berthaultii Hawkes, a close relative of S. tarijense, on which some feeding occurred and adults did not show falling behaviour. This study presents information on S. tarijense as a new source of resistance to the Colorado potato beetle that can be used for potato breeding.     

Mass mortality events in atoll lagoons: environmental control and increased future vulnerability

Coral reefs and lagoons worldwide are vulnerable environments. However, specific geomorphological reef types (fringing, barrier, atoll, bank for the main ones) can be vulnerable to specific disturbances that will not affect most other reefs. This has implications for local management and science priorities. Several geomorphologically closed atolls of the Pacific Ocean have experienced in recent decades mass benthic and pelagic lagoonal life mortalities, likely triggered by unusually calm weather conditions lasting for several weeks. These events, although poorly known, reported, and characterized, pose a major threat for resource sustainability. Based on a sample of eleven events on eight atolls from the central South Pacific occurring between 1993 and 2012, the conservative environmental thresholds required to trigger such events are identified using sea surface temperature, significant wave height and wind stress satellite data. Using these thresholds, spatial maps of potential risk are produced for the central South Pacific region, with the highest risk zone lying north of Tuamotu Archipelago. A regional climate model, which risk map compares well with observations over the recent period (r = 0.97), is then used to downscale the projected future climate. This allows us to estimate the potential change in risk by the end of the 21^st century and highlights a relative risk increase of up to 60% for the eastern Tuamotu atolls. However, the small sample size used to train the analysis led to the identification of conservative thresholds that overestimated the observed risk. The results of this study suggest that long‐term monitoring of the biophysical conditions of the lagoons at risk would enable more precise identification of the physical thresholds and better understanding of the biological processes involved in these rare, but consequential, mass mortality events.     

Detecting coevolving positions in a molecule: why and how to account for phylogeny

Positions in a molecule that share a common constraint do not evolve independently, and therefore leave a signature in the patterns of homologous sequences. Exhibiting such positions with a coevolution pattern from a sequence alignment has great potential for predicting functional and structural properties of molecules through comparative analysis. This task is complicated by the existence of additional correlation sources, leading to false predictions. The nature of the data is a major source of noise correlation: sequences are taken from individuals with different degrees of relatedness, and who therefore are intrinsically correlated. This has led to several method developments in different fields that are potentially confusing for non-expert users interested in these methodologies. It also explains why coevolution detection methods are largely unemployed despite the importance of the biological questions they address. In this article, I focus on the role of shared ancestry for understanding molecular coevolution patterns. I review and classify existing coevolution detection methods according to their ability to handle shared ancestry. Using a ribosomal RNA benchmark data set, for which detailed knowledge of the structure and coevolution patterns is available, I demonstrate and explain why taking the underlying evolutionary history of sequences into account is the only way to extract the full coevolution signal in the data. I also evaluate, using rigorous statistical procedures, the best approaches to do so, and discuss several important biological aspects to consider when performing coevolution analyses.     

Expression,localization and possible functions of aquaporins 3 and 8 in rat digestive system

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.     

Reflooding the Faguibine floodplain system,northern Mali: potential benefits and challenges

The Faguibine system, northern Mali, consists of a series of interconnected floodplains of which the flooded surface area declined from about 1 000 km² in the late 19th century to only some 90 km² in 2010. Flood extent depends on the height of the Niger River flood peak at Diré. Satellite imagery analysis indicated that a phase shift may have occurred in the year 2000, probably as a delayed consequence of the Sahelian drought of the 1970s compounded by the collapse of societal controls on water use during recent civil conflict. An economic evaluation of the system in 2011 showed US$100 000 per year of net income per flooded km² in Lake Faguibine, allowing vulnerable people to practise recession agriculture, to fish and to graze livestock. An intensive investment phase, combined with an approach of rebuilding local governance systems and environmental management capacity, could yield net benefits to the user communities of the order of ten times the maintenance costs, contributing to human well-being. The system is currently threatened by the building of the Fomi Dam in Guinea and by the planned expansion of irrigation upstream. There is also a risk of the return of a prolonged drought linked to the Atlantic multi-decadal oscillation index.     

Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

Polyethylene glycol (PEG), a high-molecular-weight colloid present in new organ preservation solutions, protects against cold ischemia injuries leading to better graft function of transplanted organs. This protective effect cannot be totally explained by immuno-camouflaging property or signaling-pathway modifications. Therefore, we sought for an alternative mechanism dependent on membrane fluidity. Using the Langmuir–Pockles technique, we show here that PEGs interacted with lipid monolayers of defined composition or constituted by a renal cell lipid extract. High-molecular-weight PEGs stabilized the lipid monolayer at low surface pressure. Paradoxically, at high surface pressure, PEGs destabilized the monolayers. Hypothermia reduced the destabilization of saturated monolayer whereas unsaturated monolayer remained unaffected. Modification of ionic strength and pH induced a stronger stabilizing effect of PEG 35,000 Da which could explain its reported higher effectiveness on cold-induced injuries during organ transplantation. This study sheds a new light on PEG protective effects during organ preservation different from all classical hypotheses.