Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate

A small library of antiplasmodial methoxy-thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepared by a simple and inexpensive procedure. The synthetic derivatives have been subjected to in vitro pharmacological screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compound 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compounds and on their putative mechanism of action.     

The dynamics of ant mosaics in tropical rainforests characterized using the Self‐Organizing Map algorithm

Ants, the most abundant taxa among canopy‐dwelling animals in tropical rainforests, are mostly represented by territorially dominant arboreal ants (TDAs) whose territories are distributed in a mosaic pattern (arboreal ant mosaics). Large TDA colonies regulate insect herbivores, with implications for forestry and agronomy. What generates these mosaics in vegetal formations, which are dynamic, still needs to be better understood. So, from empirical research based on 3 Cameroonian tree species (Lophira alata, Ochnaceae; Anthocleista vogelii, Gentianaceae; and Barteria fistulosa, Passifloraceae), we used the Self‐Organizing Map (SOM, neural network) to illustrate the succession of TDAs as their host trees grow and age. The SOM separated the trees by species and by size for L. alata, which can reach 60 m in height and live several centuries. An ontogenic succession of TDAs from sapling to mature trees is shown, and some ecological traits are highlighted for certain TDAs. Also, because the SOM permits the analysis of data with many zeroes with no effect of outliers on the overall scatterplot distributions, we obtained ecological information on rare species. Finally, the SOM permitted us to show that functional groups cannot be selected at the genus level as congeneric species can have very different ecological niches, something particularly true for Crematogaster spp., which include a species specifically associated with B. fistulosa, nondominant species and TDAs. Therefore, the SOM permitted the complex relationships between TDAs and their growing host trees to be analyzed, while also providing new information on the ecological traits of the ant species involved.     

Structure‐Activity Relationships Analysis of Monomeric and Polymeric Polyphenols (Quercetin,Rutin and Catechin) Obtained by Various Polymerization Methods

Plant polyphenols, especially flavonoids, are active and pro‐health substances found in fruits and vegetables. Quercetin and its glycoside rutin are representatives of flavonoids, commonly found in plant products. Catechins found in large quantities in tea are also a well‐known group of natural polyphenols. These compounds are based on the structure of flavan‐3‐ol, which is why the number, positions and types of substitutions affect the scavenging of radicals and other properties. Despite some inconsistent evidence, several structure?activity relationships of monomeric flavonoids are well established in vitro. However, the relationships between the activity and other properties of the polymeric forms of flavonoids and their structures are poorly understood so far. The aim of this article is to compare the data on polymerization of quercetin, rutin and catechin, as well as to systematize knowledge about the structure?activity relationship of the polymeric forms of these compounds.     

Reconciliation and third‐party affiliation in carrion crows

Conflicts are costly because they can damage social relationships. To buffer conflicts, various species use post‐conflict behaviour, such as reconciliation or third‐party affiliation. Both behaviours have predominantly been studied in non‐human primates. However, recently, studies revealed post‐conflict behaviour in other mammalian and some bird species (e.g., corvids). While third‐party affiliation has been reported in several corvid species, reconciliation has only rarely been observed. The social structure of the studied groups has been postulated as a reason for the absence of reconciliation. Here, we investigated whether post‐conflict behaviours in corvids indeed mirror the relationship structure. We studied the behaviour of a newly established group of juvenile carrion crows (Corvus corone corone), where pair bonds had not yet been established. We applied a combination of observations and food monopolisation experiments to quantify the use of post‐conflict behaviours. Provisioning food in one or two pieces induced different patterns of aggression during feeding and differently affected the affiliation patterns after feeding. Specifically, victims of severe aggression affiliated with third parties after conflicts in the two‐piece condition, while aggressors affiliated with victims of mild aggression in the one‐piece condition. We thus provide the first evidence that a corvid species, crows, flexibly engage in both third‐party affiliation and reconciliation.     

Addressing high excitation conditions in time-resolved X-ray diffraction experiments and issues of biological relevance

One of the most important fundamental questions connecting chemistry to biology is how chemistry scales in complexity up to biological systems where there are innumerable possible pathways and competing processes. With the development of ultrabright electron and x-ray sources, it has been possible to literally light up atomic motions to directly observe the reduction in dimensionality in the barrier crossing region to a few key reaction modes. How do these chemical processes further couple to the surrounding protein or macromolecular assembly to drive biological functions? Optical methods to trigger photoactive biological processes are needed to probe this issue on the relevant timescales. However, the excitation conditions have been in the highly nonlinear regime, which questions the biological relevance of the observed structural dynamics.     

Differential modulation of murine host immune response by salivary gland extracts from the mosquitoes Aedes aegypti and Culex quinquefasciatus

Mosquitoes (Diptera: Culicidae) are major vectors of numerous infectious agents. Compounds in mosquito saliva not only facilitate blood-feeding, but may also have an impact upon the immune system of vertebrate hosts. Consequently, the exposure to mosquito saliva may influence pathogen transmission, establishment and disease development. Using two medically important vector mosquitoes, Aedes aegypti (L.) and Culex quinquefasciatus Say, we examined the effects of mosquito saliva on immune cells of host mice. After antigen-specific or non-specific stimulation, murine splenocyte proliferation and production of both Th1 and Th2 cytokines were significantly reduced in the presence of salivary gland extract (SGE) from Ae. aegypti, but not SGE from Cx. quinquefasciatus. T cell populations were highly susceptible to this suppression, showing increased mortality and reduced division rates - judged by flow cytometric analyses. Evidently these two culicine mosquitoes differ in their host immunomodulatory activities.     

Metabolic and functional diversity of saponins,biosynthetic intermediates and semi-synthetic derivatives

Abstract

Saponins are widely distributed plant natural products with vast structural and functional diversity. They are typically composed of a hydrophobic aglycone, which is extensively decorated with functional groups prior to the addition of hydrophilic sugar moieties, to result in surface-active amphipathic compounds. The saponins are broadly classified as triterpenoids, steroids or steroidal glycoalkaloids, based on the aglycone structure from which they are derived. The saponins and their biosynthetic intermediates display a variety of biological activities of interest to the pharmaceutical, cosmetic and food sectors. Although their relevance in industrial applications has long been recognized, their role in plants is underexplored. Recent research on modulating native pathway flux in saponin biosynthesis has demonstrated the roles of saponins and their biosynthetic intermediates in plant growth and development. Here, we review the literature on the effects of these molecules on plant physiology, which collectively implicate them in plant primary processes. The industrial uses and potential of saponins are discussed with respect to structure and activity, highlighting the undoubted value of these molecules as therapeutics.     

DNA sequence analyses of the ribosomal spacer regions in theTriticeae

Two regions of the ribosomal DNA (rDNA) were sequenced from a range of species from the tribeTriticeae. One region, the central spacer, was found to be more divergent in sequence than the other, the 18 S-spacer junction. Both regions contained sequences 20–30 bp long which were more highly conserved than the remainder of the region and their possible significance in rDNA expression is discussed. Phenetic relationships based on the sequence data were generally consistent with the relationships based on other criteria. Species possessing the S, E, J₁J₂, D, and B genomes clustered together, with the H genome species being the most distinct of those examined. The R, P, and V genome species occupy an intermediate position in the overall pattern of relationships. Some relationships differed in detail from those established by other parameters, for example the position of the N genome species, and explanations for discrepancies of this type are discussed.