γ-Lactam-Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC₅₀ around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy.     

Cytochalasin D inhibits basal body migration and ciliary elongation in quail oviduct epithelium

Summary The effects of cytochalasin D (CD) were studied by scanning (SEM) and transmission (TEM) electron-microscopic examination at different stages of ciliary differentiation in epithelial cells of quail oviduct. Immature quails were prestimulated by estradiol benzoate injections to induce ciliogenesis in the undifferentiated oviduct. After 24 h of CD culture, SEM study revealed inhibition of ciliogenesis and dilation of the apex of non-ciliated cells. TEM study showed that 2 h of CD treatment produced dilation of lateral intercellular spaces, after 6 h of treatment, this resulted in intracellular macrovacuolation. Vacuoles were surrounded by aggregates of dense felt-like material. CD also induced the disappearance of microvilli, and rounding of the apical surface of undifferentiated cells and those blocked in ciliogenesis. Centriologenesis was not inhibited by CD; basal bodies assembled in generative complexes in the supranuclear region after 24 h of treatment. However, the migration of mature basal bodies towards the apical surface was impaired. Instead, they anchored onto the membrane of intracellular vacuoles; growth of cilia was induced in the vacuole lumen. Cilium elongation was disturbed, giving abnormally short cilia with a dilated tip; microtubules failed to organize correctly.     

Efficacy of handrubbing with alcohol based solution versus standard handwashing with antiseptic soap: randomised clinical trial

ObjectiveTo compare the efficacy of handrubbing with an alcohol based solution versus conventional handwashing with antiseptic soap in reducing hand contamination during routine patient care.DesignRandomised controlled trial during daily nursing sessions of 2 to 3 hours.SettingThree intensive care units in a French university hospital.Participants23 healthcare workers.InterventionsHandrubbing with alcohol based solution (n=12) or handwashing with antiseptic soap (n=11) when hand hygiene was indicated before and after patient care. Imprints taken of fingertips and palm of dominant hand before and after hand hygiene procedure. Bacterial counts quantified blindly.ResultsWith handrubbing the median percentage reduction in bacterial contamination was significantly higher than with handwashing (83% v 58%, P=0.012), with a median difference in the percentage reduction of 26% (95% confidence interval 8% to 44%). The median duration of hand hygiene was 30 seconds in each group.ConclusionsDuring routine patient care handrubbing with an alcohol based solution is significantly more efficient in reducing hand contamination than handwashing with antiseptic soap.

What is already known on this topic

To improve compliance with hand hygiene during patient care, handrubbing with an alcohol based solution has been proposed as a substitute for handwashing because of its rapid action and accessibilityExperimental studies show that handrubbing is at least as effective as medicated soap in reducing artificial contamination of handsMany healthcare workers still have reservations regarding its efficacy and are reluctant to use this technique

What this study adds

When used in routine practice, handrubbing with an alcohol based solution after contact with patients achieved a greater reduction in bacterial contamination of hands than conventional handwashing with medicated soap     

Sex-biased dispersal promotes adaptive parental effects

Background  

In heterogeneous environments, sex-biased dispersal could lead to environmental adaptive parental effects, with offspring selected to perform in the same way as the parent dispersing least, because this parent is more likely to be locally adapted. We investigate this hypothesis by simulating varying levels of sex-biased dispersal in a patchy environment. The relative advantage of a strategy involving pure maternal (or paternal) inheritance is then compared with a strategy involving classical biparental inheritance in plants and in animals.     

Rab6 and the secretory pathway affect oocyte polarity in Drosophila

The Drosophila oocyte is a highly polarized cell. Secretion occurs towards restricted neighboring cells and asymmetric transport controls the localization of several mRNAs to distinct cortical compartments. Here, we describe a role for the Drosophila ortholog of the Rab6 GTPase, Drab6, in establishing cell polarity during oogenesis. We found that Drab6 localizes to Golgi and Golgi-derived membranes and interacts with BicD. We also provide evidence that Drab6 and BicD function together to ensure the correct delivery of secretory pathway components, such as the TGFalpha homolog Gurken, to the plasma membrane. Moreover, in the absence of Drab6, osk mRNA localization and the organization of microtubule plus-ends at the posterior of the oocyte were both severely affected. Our results point to a possible connection between Rab protein-mediated secretion, organization of the cytoskeleton and mRNA transport.     

Evolutionary history of aphid-plant associations and their role in aphid diversification

Aphids are intimately linked with their host plants that constitute their only food resource and habitat, and thus impose considerable selective pressure on their evolution. It is therefore commonly assumed that host plants have greatly influenced the diversification of aphids. Here, we review what is known about the role of host plant association on aphid speciation by examining both macroevolutionary and population-level studies. Phylogenetic studies conducted at different taxonomic levels show that, as in many phytophagous insect groups, the radiation of angiosperms has probably favoured the major Tertiary diversification of aphids. These studies also highlight many aphid lineages constrained to sets of related host plants, suggesting strong evolutionary commitment in aphids’ host plant choice, but they fail to document cospeciation events between aphid and host lineages. Instead, phylogenies of several aphid genera reveal that divergence events are often accompanied by host shifts, and suggest, without constituting a formal demonstration, that aphid speciation could be a consequence of adaptation to new hosts. Experimental and field studies below the species level support reproductive isolation between host races as partly due to divergent selection by their host plants. Selected traits are mainly feeding performances and life cycle adaptations to plant phenology. Combined with behavioural preference for favourable host species, these divergent adaptations can induce pre- and post-zygotic barriers between host-specialized aphid populations. However, the hypothesis of host-driven speciation is seldom tested formally and must be weighed against overlooked explanations involving geographic isolation and non-ecological reproductive barriers in the process of speciation.     

Proteomic studies highlight outer‐membrane proteins related to biofilm development in the marine bacterium Pseudoalteromonas sp. D41

Bacterial biofilm development is conditioned by complex processes involving bacterial attachment to surfaces, growth, mobility, and exoproduct production. The marine bacterium Pseudoalteromonas sp. strain D41 is able to attach strongly onto a wide variety of substrates, which promotes subsequent biofilm development. Study of the outer‐membrane and total soluble proteomes showed ten spots with significant intensity variations when this bacterium was grown in biofilm compared to planktonic cultures. MS/MS de novo sequencing analysis allowed the identification of four outer‐membrane proteins of particular interest since they were strongly induced in biofilms. These proteins are homologous to a TonB‐dependent receptor (TBDR), to the OmpW and OmpA porins, and to a type IV pilus biogenesis protein (PilF). Gene expression assays by quantitative RT‐PCR showed that the four corresponding genes were upregulated during biofilm development on hydrophobic and hydrophilic surfaces. The Pseudomonas aeruginosa mutants unable to produce any of the OmpW, OmpA, and PilF homologues yielded biofilms with lower biovolumes and altered architectures, confirming the involvement of these proteins in the biofilm formation process. Our results indicate that Pseudoalteromonas sp. D41 shares biofilm formation mechanisms with human pathogenic bacteria, but also relies on TBDR, which might be more specific to the marine environment.     

Synthesis and biological activity of 2-aminothiazoles as novel inhibitors of PGE2 production in cells

This Letter presents the synthesis and biological evaluation of a collection of 2-aminothiazoles as a novel class of compounds with the capability to reduce the production of PGE(2) in HCA-7 human adenocarcinoma cells. A total of 36 analogs were synthesized and assayed for PGE(2) reduction, and those with potent cellular activity were counter screened for inhibitory activity against COX-2 in a cell free assay. In general, analogs bearing a 4-phenoxyphenyl substituent in the R(2) position were highly active in cells while maintaining negligible COX-2 inhibition. Specifically, compound 5l (R(1)=Me, R(2)=4-OPh-Ph, R(3)=CH(OH)Me) exhibited the most potent cellular PGE(2) reducing activity of the entire series (EC(50)=90 nM) with an IC(50) value for COX-2 inhibition of >5 μM in vitro. Furthermore, the anti-tumor activity of analog 1a was analyzed in xenograft mouse models exhibiting promising anti-cancer activity.