Influence of geography, seasons and pedology on chemical composition and anti-inflammatory activities of essential oils from Lippia multiflora Mold leaves.

Ethnopharmacological Relevance: Lippia multiflora is a plant with nutritional and pharmaco-therapeutic properties that is native to central and occidental Africa. The potential effects of plants on health are associated with their chemical composition. Therefore, the present study aimed to identify chemical variations in essential oils of Lippia multiflora as a function of geographic origin and time of annual harvest to determine optimal chemical profiles for ethno-pharmacotherapeutic applications.

Analysis of emerging contaminants in water and solid samples using high resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic activity with YES-assay.

Trace emerging contaminants (ECs) occur in both waste and surface waters that are rich in particulates that have been found to sorb several organic contaminants. An analytical method based on off-line solid-phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS) analysis was developed for the detection and quantification of 31 ECs from surface water, wastewater, suspended particulate matter (SPM) as well as sediments. Lyophilized sediments and air-dried SPM were subjected to ultrasonic extraction.

Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog.

While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270(T) and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidans (T), the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied.

Synthesis of novel C-symmetric testosterone dimers and evaluation of antiproliferative activity on androgen-dependent and -independent prostate cancer cell lines.

A series of 7α-linked testosterone dimers were made and tested for biological activity on both androgen-dependent (LNCaP) and androgen-independent (DU-145 and PC3) prostate cancer cell lines. The synthesis proceeds through the formation of a trans-4-(17β-acetoxy-4-androsten-3-one-7α-yl)-but-2-enoic acid 4-hydroxy-alkyl ester intermediate of various length (7a-d) followed by the final dimerization step. The dimers showed interesting biological activity in comparison to the ω-hydroxyalkyl ester intermediates 7a-d.

Structural Characterization of a Novel Antioxidant Pigment Produced by a Photochromogenic Microbacterium oxydans Strain.

The Microbacteriaceae family, such as Microbacterium, is well known for its ability to produce carotenoid-type pigments, but little has been published on the structure of such pigments. Here, we isolated the yellow pigment that is responsible for the yellowish color of a Microbacterium oxydans strain isolated from a decomposing stump of a resinous tree. The pigment, which is synthesized when the bacterium is grown under light, was purified and characterized using several spectroscopic analyses, such as ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), H and C nuclear magnetic resonance (H NMR, C NMR), and high-resolution mass spectrometry (HRMS).

Synthesis of γ,δ-Unsaturated α-Aminoaldehydes Using a Copper-Catalyzed Vinylation Reaction Followed by a Claisen Rearrangement.

A new method to synthesize γ,δ-unsaturated α-nitrogenated aldehydes in very good yields is described herein. This method involves a copper-coupling reaction between β-iodoenamide derivatives and allylic alcohols to generate β-allyloxyenamide derivatives. The latter, when heated, undergo a Claisen rearrangement and form γ,δ-unsaturated α-nitrogenated aldehydes.

Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses.

Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use.

Studying illicit drug trafficking on Darknet markets: Structure and organisation from a Canadian perspective.

Cryptomarkets are online marketplaces that are part of the Dark Web and mainly devoted to the sale of illicit drugs. They combine tools to ensure anonymity of participants with the delivery of products by mail to enable the development of illicit drug trafficking. Using data collected on eight cryptomarkets, this study provides an overview of the Canadian illicit drug market.

Hierarchy and extremes in selections from pools of randomized proteins.

Variation and selection are the core principles of Darwinian evolution, but quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display, and analyzed their response to selection by high-throughput sequencing.

Individuality and universality in the growth-division laws of single E. coli cells.

The mean size of exponentially dividing Escherichia coli cells in different nutrient conditions is known to depend on the mean growth rate only. However, the joint fluctuations relating cell size, doubling time, and individual growth rate are only starting to be characterized. Recent studies in bacteria reported a universal trend where the spread in both size and doubling times is a linear function of the population means of these variables.

The role of H2O in the electron transfer-activation of substrates using SmI2: insights from DFT.

The first detailed theoretical study on the synthetically important electron transfer (ET) reductant SmI2-H2O has been conducted in the context of the activation of important alkyliodide, ketone, lactone and ester substrates, processes of importance in cross-coupling. Our studies give major insights into the nature of the reagent and suggest that; (i) H2O has a high affinity for Sm(ii) and displaces iodine from the metal center; (ii) SmI2-H2O has 6-7 molecules of H2O directly bound to the metal center; (iii) binding of H2O to Sm(II) promotes coordination of the substrate to Sm(II) and subsequent ET; (iv) resultant ketyl radicals are stabilized by hydrogen-bonding to H2O. The findings add greatly to the understanding of SmI2-H2O and the role of H2O in ET processes, and will facilitate the design of new processes initiated by reductive ET.

The use of isomeric testosterone dimers to explore allosteric effects in substrate binding to cytochrome P450 CYP3A4.

Cytochrome P450 CYP3A4 is the main drug-metabolizing enzyme in the human liver, being responsible for oxidation of 50% of all pharmaceuticals metabolized by human P450 enzymes. Possessing a large substrate binding pocket, it can simultaneously bind several substrate molecules and often exhibits a complex pattern of drug-drug interactions. In order to better understand structural and functional aspects of binding of multiple substrate molecules to CYP3A4 we used resonance Raman and UV-VIS spectroscopy to document the effects of binding of synthetic testosterone dimers of different configurations, cis-TST2 and trans-TST2.

An overview of molecular hybrids in drug discovery.

Introduction: The hybridization of biologically active molecules is a powerful tool for drug discovery used to target a variety of diseases. It offers the prospect of better drugs for the treatment of a number of illnesses including cancer, malaria, tuberculosis and AIDS. Hybrid drugs can provide combination therapies in a single multi-functional agent and, by doing so, be more specific and powerful than conventional classic treatments.

Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.

Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis.

Cost-effectiveness analysis of antiviral treatment in the management of seasonal influenza A: point-of-care rapid test versus clinical judgment.

Background: A point-of-care rapid test (POCRT) may help early and targeted use of antiviral drugs for the management of influenza A infection.

Objective: (i) To determine whether antiviral treatment based on a POCRT for influenza A is cost-effective and, (ii) to determine the thresholds of key test parameters (sensitivity, specificity and cost) at which a POCRT based-strategy appears to be cost effective.

Methods: An hybrid « susceptible, infected, recovered (SIR) » compartmental transmission and Markov decision analytic model was used to simulate the cost-effectiveness of antiviral treatment based on a POCRT for influenza A in the social perspective.

In situ and real time investigation of the evolution of a Pseudomonas fluorescens nascent biofilm in the presence of an antimicrobial peptide.

Against the increase of bacterial resistance to traditional antibiotics, antimicrobial peptides (AMP) are considered as promising alternatives. Bacterial biofilms are more resistant to antibiotics that their planktonic counterpart. The purpose of this study was to investigate the action of an AMP against a nascent bacterial biofilm.

Crystal-clear - The '2014 Most Superlative Crystal Growth Contest' for School Classes.

To celebrate the International Year of Crystallography among the general public, a consortium of chemists, physicists and crystallographers of the University of Geneva organised in Spring 2014 an incentive crystal growth contest for Geneva scholars aged 4 to 19. Starting from a kit containing a salt and user instructions, classes had to prepare a crystal that met specific criteria according to their category of age. The composition of the salt - potassium dihydrogen phosphate (KDP) - was only disclosed to the participants during the final Awards Ceremony.

[Randomness and cell fate].

Thermal fluctuations at the molecular scale cause random fluctuations of gene expression, which, in association with differentiation circuits, can lead to phenotypic diversification in cell populations. In this synthesis article, we detail the mechanisms that generate this diversification and illustrate their consequences in various organisms. In bacteria, random phenotypic diversification allows to anticipate environmental changes that are otherwise unpredictable, in particular during metabolic transitions and stress responses, for example inducing a transient form of antibiotic resistance.

Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

Background: Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites sharing a common biosynthetic origin beginning with tyrosine. Many BIAs have potent pharmacological activities, and plants accumulating them boast long histories of use in traditional medicine and cultural practices. The decades-long focus on a select number of plant species as model systems has allowed near or full elucidation of major BIA pathways, including those of morphine, sanguinarine and berberine.

Condensin- and Replication-Mediated Bacterial Chromosome Folding and Origin Condensation Revealed by Hi-C and Super-resolution Imaging.

Chromosomes of a broad range of species, from bacteria to mammals, are structured by large topological domains whose precise functional roles and regulatory mechanisms remain elusive. Here, we combine super-resolution microscopies and chromosome-capture technologies to unravel the higher-order organization of the Bacillus subtilis chromosome and its dynamic rearrangements during the cell cycle. We decipher the fine 3D architecture of the origin domain, revealing folding motifs regulated by condensin-like complexes.

Sulfur vesicles from Thermococcales: A possible role in sulfur detoxifying mechanisms.

The euryarchaeon Thermococcus prieurii inhabits deep-sea hydrothermal vents, one of the most extreme environments on Earth, which is reduced and enriched with heavy metals. Transmission electron microscopy and cryo-electron microscopy imaging of T. prieurii revealed the production of a plethora of diverse membrane vesicles (MVs) (from 50 nm to 400 nm), as is the case for other Thermococcales.

Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats.

A diet enriched with citrulline (CIT) reduces white adipose tissue (WAT) mass. We recently showed that CIT stimulated β-oxidation in rat WAT explants from young (2-4 months) but not old (25 months) rats. Here we show that both in old rats and high-fat-diet-fed young rats, uncoupling protein one (UCP1) mRNA and protein expressions were weaker than those in young control rats.

Characterization of the structural changes and photochemical activity of photosystem I under Al(3+) effect.

The photochemical activity of photosystem I (PSI) as affected by Al(3+) was investigated in thylakoid membranes and PSI submembrane fractions isolated from spinach. Biophysical and biochemical techniques such as oxygen uptake, light induced absorbance changes at 820nm, chlorophyll fluorescence emission, SDS-polyacrylamide gel electrophoresis, and FTIR spectroscopy have been used to analyze the sites and action modes of this cation on the PSI complex. Our results showed that Al(3+) above 3mM induces changes in the redox state of P700 reflected by an increase of P700 photooxidation phase and a delay of the slower rate of P700 re-reduction which reveals that Al(3+) exerted an inhibitory action at the donor side of PSI especially at plastocyanin (PC).

The end of the (forensic science) world as we know it? The example of trace evidence.

The dominant conception of forensic science as a patchwork of disciplines primarily assisting the criminal justice system (i.e. forensics) is in crisis or at least shows a series of anomalies and serious limitations.

Exploring the synthesis and anticancer potential of L-tyrosine-platinum(II) hybrid molecules.

The search for new specific chemotherapeutic drugs designed to minimize the toxic side effects resulting from chemotherapy is still a subject of intense research. The objective of the current study was to design a non-steroidal-platinum(II) derivative that would target the estrogen receptor alpha (ERα) without triggering estrogenic cell proliferation. For this purpose, the amino acid L-tyrosine was modified and attached to a cisplatin analog.