The Polyphenol Piceid Destabilizes Preformed Amyloid Fibrils and Oligomers In Vitro: Hypothesis on Possible Molecular Mechanisms

Alzheimer’s disease (AD) is characterized by deposits of amyloid in various tissues. The neuronal cytotoxicity of Aβ peptides is attributed not only to various mechanisms but also to amyloid fibrils and soluble oligomeric intermediates. Consequently, finding molecules to prevent or reverse the oligomerization and fibrillization of Aβ could be of therapeutic value in the treatment of AD. We show that piceid, a polyphenol of the stilbene family, destabilized fibrils and oligomers to give back monomers that are not neurotoxic molecules. The mechanism of this destabilization could be a dynamic interaction between the polyphenol and the Aβ that could open the hydrophobic zipper and shift the reversible equilibrium “random coil⇔β-sheet” to the disordered structure.     

New in vitro colonic fermentation model for Salmonella infection in the child gut

In this study, a new in vitro continuous colonic fermentation model of Salmonella infection with immobilized child fecal microbiota and Salmonella serovar Typhimurium was developed for the proximal colon. This model was then used to test the effects of two amoxicillin concentrations (90 and 180 mg day⁻¹) on the microbial composition and metabolism of the gut microbiota and on Salmonella serovar Typhimurium during a 43-day fermentation. Addition of gel beads (2%, v/v) colonized with Salmonella serovar Typhimurium in the reactor resulted in a high and stable Salmonella concentration (log 7.5 cell number mL⁻¹) in effluent samples, and a concomitant increase of Enterobacteriaeceae, Clostridium coccoides–Eubacterium rectale and Atopobium populations and a decrease of bifidobacteria. During amoxicillin treatments, Salmonella concentrations decreased while microbial balance and activity were modified in agreement with in vivo data, with a marked decrease in C. coccoides–E. rectale and an increase in Enterobacteriaceae . After interruption of antibiotic addition, Salmonella concentration again increased to reach values comparable to that measured before antibiotic treatments, showing that our model can be used to simulate Salmonella shedding in children as observed in vivo . This in vitro model could be a useful tool for developing and testing new antimicrobials against enteropathogens.     

What Triggers Reproductive Life? Effects of Adolescent Cohabitation,Social Novelty and Aggression in a Monogamous Mouse

Cohabitation during childhood has been described as a powerful inhibitor of later sexual interest in animals including humans (the 'Westermarck effect'), serving as a brother–sister incest avoidance mechanism. Mound-building mice Mus spicilegus display a strong social inhibition of reproduction, responsible for the absence of reproduction in over-wintering tumuli. To better understand the mechanisms responsible for triggering reproduction in this monogamous species, we formed 100 experimental couples of juveniles (35 d) and surveyed reproduction for 45 d. As expected, very few couples reproduced, which confirms the role of social familiarity in the inhibition of reproduction. Temporary separation (1 h or 24 h) of the two partners had little effect on reproductive success. However, pairing with a new partner, with or without prior isolation, significantly triggered reproduction. Observations of the first encounter between new partners revealed more agonistic and less affiliative behaviour than in controls (reunion of familiar partners). Interestingly, when the new partner was a sibling of the previous one, the behavioural analysis revealed an intermediate level of aggression, indicating that kinship with the previous partner was perceived and had consequences on social behaviour. Mice could therefore choose a new partner based on its relatedness to the previous mate. Mutual tolerance between new partners during the dyadic encounter was negatively correlated with subsequent reproduction. These results demonstrate the paramount role of social novelty in triggering reproduction in this monogamous mouse, and suggest a link between agonistic behaviour and sexual motivation. In the field, mound-building mice may need to engage in agonistic interactions so as to overcome the long-lasting social inhibition of reproduction in overwintering mounds.     

Structural analysis of a glycoside hydrolase family 43 arabinoxylan arabinofuranohydrolase in complex with xylotetraose reveals a different binding mechanism compared with other members of the same family

AXHs (arabinoxylan arabinofuranohydrolases) are alpha-L-arabinofuranosidases that specifically hydrolyse the glycosidic bond between arabinofuranosyl substituents and xylopyranosyl backbone residues of arabinoxylan. Bacillus subtilis was recently shown to produce an AXH that cleaves arabinose units from O-2- or O-3-mono-substituted xylose residues: BsAXH-m2,3 (B. subtilis AXH-m2,3). Crystallographic analysis reveals a two-domain structure for this enzyme: a catalytic domain displaying a five-bladed beta-propeller fold characteristic of GH (glycoside hydrolase) family 43 and a CBM (carbohydrate-binding module) with a beta-sandwich fold belonging to CBM family 6. Binding of substrate to BsAXH-m2,3 is largely based on hydrophobic stacking interactions, which probably allow the positional flexibility needed to hydrolyse both arabinose substituents at the O-2 or O-3 position of the xylose unit. Superposition of the BsAXH-m2,3 structure with known structures of the GH family 43 exo-acting enzymes, beta-xylosidase and alpha-L-arabinanase, each in complex with their substrate, reveals a different orientation of the sugar backbone.     

Cadmium uptake and distribution in Arabidopsis thaliana exposed to low chronic concentrations depends on plant growth

This study tested the hypothesis that Cd uptake is correlated with the shoot or root growth of Arabidopsis thaliana ecotype Columbia cultivated hydroponically at environmentally relevant Cd concentrations: 20, 100 and 350 nmol L^?1. Growth of both roots and shoots were delayed at 350 nmol L^?1. The rate of Cd uptake determined by spiking the nutrient solution with ¹⁰⁹Cd for 24 h, was significantly correlated with the root growth rate. The fraction of Cd absorbed that was allocated to shoots was constant with time but decreased with increasing exposure to Cd. Autoradiography and gamma counting showed that Cd was preferentially allocated to developing leaves. Hence, the quantity of Cd in shoots depended both on the root growth, which probably governed the uptake, and on the maturity of the leaves, which may have determined the Cd allocated to shoots through changes in the transpiration stream.     

Salicylic Acid Transport in Ricinus communis Involves a pH-Dependent Carrier System in Addition to Diffusion

Despite its important functions in plant physiology and defense, the membrane transport mechanism of salicylic acid (SA) is poorly documented due to the general assumption that SA is taken up by plant cells via the ion trap mechanism. Using Ricinus communis seedlings and modeling tools (ACD LogD and Vega ZZ softwares), we show that phloem accumulation of SA and hydroxylated analogs is completely uncorrelated with the physicochemical parameters suitable for diffusion (number of hydrogen bond donors, polar surface area, and, especially, LogD values at apoplastic pHs and Δ LogD between apoplast and phloem sap pH values). These and other data (such as accumulation in phloem sap of the poorly permeant dissociated form of monohalogen derivatives from apoplast and inhibition of SA transport by the thiol reagent p-chloromercuribenzenesulfonic acid [pCMBS]) lead to the following conclusions. As in intestinal cells, SA transport in Ricinus involves a pH-dependent carrier system sensitive to pCMBS; this carrier can translocate monohalogen analogs in the anionic form; the efficiency of phloem transport of hydroxylated benzoic acid derivatives is tightly dependent on the position of the hydroxyl group on the aromatic ring (SA corresponds to the optimal position) but moderately affected by halogen addition in position 5, which is known to increase plant defense. Furthermore, combining time-course experiments and pCMBS used as a tool, we give information about the localization of the SA carrier. SA uptake by epidermal cells (i.e. the step preceding the symplastic transport to veins) insensitive to pCMBS occurs via the ion-trap mechanism, whereas apoplastic vein loading involves a carrier-mediated mechanism (which is targeted by pCMBS) in addition to diffusion.     

CFTR mediates cadmium-induced apoptosis through modulation of ROS level in mouse proximal tubule cells

The aim of this study was to characterize the role of CFTR during Cd²⁺-induced apoptosis. For this purpose primary cultures and cell lines originated from proximal tubules (PCT) of wild-type cftr^+/+ and cftr^?/? mice were used. In cftr^+/+ cells, the application of Cd²⁺ (5 μM) stimulated within 8 min an ERK1/2-activated CFTR-like Cl^? conductance sensitive to CFTR_inh-172. Thereafter Cd²⁺ induced an apoptotic volume decrease (AVD) within 6 h followed by caspase-3 activation and apoptosis. The early increase in CFTR conductance was followed by the activation of volume-sensitive outwardly rectifying (VSOR) Cl^? and TASK2 K⁺ conductances. By contrast, cftr^?/? cells exposed to Cd²⁺ were unable to develop VSOR currents, caspase-3 activity, and AVD process and underwent necrosis. Moreover in cftr^+/+ cells, Cd²⁺ enhanced reactive oxygen species (ROS) production and induced a 50% decrease in total glutathione content (major ROS scavenger in PCT). ROS generation and glutathione decrease depended on the presence of CFTR, since they did not occur in the presence of CFTR_inh-172 or in cftr^?/? cells. Additionally, Cd²⁺ exposure accelerates effluxes of fluorescent glutathione S-conjugate in cftr^+/+ cells. Our data suggest that CFTR could modulate ROS levels to ensure apoptosis during Cd²⁺ exposure by modulating the intracellular content of glutathione.     

On the importance of estimating detection probabilities from at‐sea surveys of flying seabirds

The primary and accepted method used to estimate seabird densities at sea from ships is the strip transect method, designed to correct for the effect of random directional bird movement relative to that of the ship. However, this method relies on the critical assumption that all of the birds within the survey strip are detected. We used the distance sampling method from line‐transects to estimate detection probability of a number of species of flying seabirds, and to test whether distance from the ship and bird body size affected detectability. Detection probability decreased from 0.987 (SE=0.029) to 0.269 (SE=0.035) with increasing strip half‐width from 100 to 1400 m. Detection probability also varied between size‐groups of species with strip half‐width. For all size‐groups, this probability was close to 1 for strip half‐width of 100 m, but was 0.869 (SE=0.115), 0.725 (SE=0.096) and 0.693 (SE=0.091) for strip half‐width of 300 m, a typical strip width used in seabird surveys, for respectively large, medium and small size flying seabirds. For larger strip half‐width, detection probability was higher for large sized species, intermediate for medium sized species and lower for smaller sized species. For strip half‐width larger than 100 m we suggest that more attention should be paid to testing the assumption of perfect detectability, because abundance estimates may be underestimated when this assumption is violated. Finally, the effect of the speed of travel of flying seabird on the detection probability was estimated in a simulation study, which suggests that detection probability was underestimated with increasing flying speed.