Variation of the Chemical Composition of Essential Oils and Total Phenols Content in Natural Populations of Marrubium vulgare L.

Marrubium vulgare is a valuable source of natural bioactive molecules with high preventive and therapeutic effectiveness. Therefore, this study aimed to study the chemical polymorphism of natural populations of M. vulgare in Tunisia by quantitative chemical markers and the estimation of divergence between populations. Phytochemical analyses of the eight natural populations of Tunisian Marrubium vulgare prospected in different bioclimatic stages, revealed 42 compounds of essential oils representing 96.08% to 100% of the total oil. Hydrocarbon sesquiterpenes were the main fraction of all the populations studied and ß-bisabolene was the major compound (from 30.11% to 71.35% of the total oil). The phytochemical investigation of the M. vulgare plant indicated the presence of essential oil with significant percentages of phenolic compounds. A significant quantitative and qualitative variation in the essential oils is detected for both major and minor compounds. The principal components analysis (PCA) performed in the single and combined traits provides a good distinction among populations, not according to their geographical and/or bioclimatic origins. Moreover, the phytochemical analysis of the leaves showed that the Tunisian populations, i.e., the populations of Kasserine, Kef, and Beja, were very rich in phenolic compounds (from 20.8 to 44.65 mg GAE/g DW). Flavonoids compounds were also the main class of total polyphenols present in all the tested populations (from 8.91 to 37.48 mg RE/g DW). The quantitative genetic diversity estimated by the population's structure, based on PCA analysis, was an adaptation to the changes in the environmental conditions. Overall, our study indicated that natural populations of M. vulgare had different chemotypes of essential oils and they were rich in phenolic compounds, particularly flavonoids, which opens a new prospect for industrial use and differential exploitation of this species.

Drought priming improves subsequent more severe drought in a drought-sensitive cultivar of olive cv. Chétoui.

Drought is a major factor limiting crop production worldwide. The objective of this study was to test whether pre-exposure to drought can enhance the subsequent drought response of a drought-sensitive variety of olive cv. Chétoui. Seven-months old olive plants were grown in a controlled conditions and divided into control plants (irrigated daily), primed plants (PP, primed by exposure to drought for 21 days, re-watered for 60 days and then exposed to water depletion for 30 days) and non-primed plants (NPP, well watered for 81 days and immediately followed by intermediate drought as PP). Compared to the non-primed plants, primed plants showed an improvement in biomass production and healthy values of photosynthesis parameters with a higher accumulation of photosynthetic pigments. Additionally, the data of chlorophyll fluorescence were significantly similar to those of control, implying that no photodamage was occurred. Moreover, primed plants exhibited high accumulation of total sugar and proline which lead to the better water status maintenance. The lower level of oxidative status measured in term of hydrogen peroxide (H2O2), malondiadehyde (MDA) and electrolyte leakage (EC) in primed plants confirmed the alleviation of oxidative stress. Furthermore, the primed plants possessed more effective oxygen scavenging systems as exemplified by the increased activities of CAT, SOD, GP and high accumulation of polyphenols, resulting in a better maintenance in homeostasis of ROS production. Our investigation is indicative of the result of the benefit memory effects caused by stress pre-exposure in young olive plants cv.'Chétoui' to overcome subsequent stress.

Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway.

Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X-ray crystal structure of human N-acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C-terminal domain, which is typical of other SAM-dependent O-methyltransferases, and an N-terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3-dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.

Fungal-induced cell cycle impairment, chromosome instability and apoptosis via differential activation of NF-κB.

Microbial pathogens have developed efficient strategies to compromise host immune responses. Cryptococcus neoformans is a facultative intracellular pathogen, recognised as the most common cause of systemic fungal infections leading to severe meningoencephalitis, mainly in immunocompromised patients. This yeast is characterized by a polysaccharide capsule, which inhibits its phagocytosis. Whereas phagocytosis escape and macrophage intracellular survival have been intensively studied, extracellular survival of this yeast and restraint of host innate immune response are still poorly understood. In this study, we have investigated whether C. neoformans affected macrophage cell viability and whether NF-κB (nuclear factor-κB), a key regulator of cell growth, apoptosis and inflammation, was involved. Using wild-type (WT) as well as mutant strains of C. neoformans for the pathogen side, and WT and mutant cell lines with altered NF-κB activity or signalling as well as primary macrophages for the host side, we show that C. neoformans manipulated NF-κB-mediated signalling in a unique way to regulate macrophage cell fate and viability. On the one hand, serotype A strains reduced macrophage proliferation in a capsule-independent fashion. This growth decrease, which required a critical dosage of NF-κB activity, was caused by cell cycle disruption and aneuploidy, relying on fungal-induced modification of expression of several cell cycle checkpoint regulators in S and G2/M phases. On the other hand, C. neoformans infection induced macrophage apoptosis in a capsule-dependent manner with a differential requirement of the classical and alternative NF-κB signalling pathways, the latter one being essential. Together, these findings shed new light on fungal strategies to subvert host response through uncoupling of NF-κB activity in pathogen-controlled apoptosis and impairment of cell cycle progression. They also provide the first demonstration of induction of aneuploidy by a fungal pathogen, which may have wider implications for human health as aneuploidy is proposed to promote tumourigenesis.