Plant-derived phenolics inhibit the accrual of structurally characterised protein and lipid oxidative modifications

Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 different plant-derived phenolic acids, we selected the most antioxidant ones. Their effect was assessed in 5 different oxidation systems, as well as in other model proteins. Mass-spectrometry was then used, evidencing a heterogeneous effect on the accumulation of the structurally characterized protein carbonyl glutamic and aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL apoprotein. After TOF based lipidomics, we identified the most abundant differential lipids in Cu(++)-incubated LDL as 1-palmitoyllysophosphatidylcholine and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds prevented the accumulation of those phospholipids and the cellular impairment induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated the effect of the intake of a phenolic-enriched extract in plasma protein and lipid modifications in a well-established model of atherosclerosis (diet-induced hypercholesterolemia in hamsters). This showed that a dietary supplement with a phenolic-enriched extract diminished plasma protein oxidative and lipid damage. Globally, these data show structural basis of antioxidant properties of plant-derived phenolic acids in protein oxidation that may be relevant for the health-promoting effects of its dietary intake.     

Peptidotriazoles with antimicrobial activity against bacterial and fungal plant pathogens

We designed and prepared peptidotriazoles based on the antimicrobial peptide BP100 (LysLysLeuPheLysLysIleLeuLysTyrLeu-NH(2)) by introducing a triazole ring in the peptide backbone or onto the side chain of a selected residue. These compounds were screened for their in vitro growth inhibition of bacterial and fungal phytopathogens, and for their cytotoxic effects on eukaryotic cells and tobacco leaves. Their proteolytic susceptibility was also analyzed. The antibacterial activity and the hemolysis were influenced by the amino acid that was modified with the triazole as well as by the absence of presence of a substituent in this heterocyclic ring. We identified sequences active against the bacteria Xanthomonas axonopodis pv. vesicatoria, Erwinia amylovora, Pseudomonas syringae pv. syringae (MIC of 1.6-12.5 μM), and against the fungi Fusarium oxysporum (MIC<6.2-12.5 μM) with low hemolytic activity (0-23% at 50 μM), high stability to protease digestion and no phytotoxicity. These peptidotriazoles constitute good candidates to design new antimicrobial agents.     

From the granary to the field; archaeobotany and experimental archaeology at l’Esquerda (Catalonia, Spain)

The study of a granary excavated at the medieval site of l’Esquerda has increased our knowledge of agricultural practices and economy. To deepen this knowledge, an experimental project was started with the late P.J. Reynolds (Butser Ancient Farm, England). Since the start of the experiment, 15 years of harvests have been collected from four fields near the archaeological site, which were cultivated with the cereals of medieval times and with a simulation of medieval farming practices. Meteorological conditions are measured by an automatic weather station, and the results are compared with those obtained in England. The research, initially started to provide more insight into crop yields, was extended towards medieval crop storage practices. The granary excavated at l’Esquerda has now been rebuilt using medieval techniques. This has allowed us to answer many questions about medieval architecture, tools and Blacksmith’s technology. Some underground pits were also dug. Experiments in crop storage using both systems are continuing.     

Beta-catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to beta-catenin

beta-Catenin plays a central role in the establishment and regulation of adherens junctions because it interacts with E-cadherin and, through alpha-catenin, with the actin cytoskeleton. beta-Catenin is composed of three domains: a central armadillo repeat domain and two N- and C-terminal tails. The C-tail interacts with the armadillo domain and limits its ability to bind E-cadherin and other cofactors. The two beta-catenin tails are mutually inter-regulated because the C-tail is also necessary for binding of the N-tail to the armadillo domain. Moreover, the N-tail restricts the interaction of the C-tail with the central domain. Depletion of either of the two tails has consequences for the binding of factors at the other end: deletion of the C-tail increases alpha-catenin binding, whereas deletion of the N-tail blocks E-cadherin interaction to the armadillo repeats. As an effect of the interconnection of the tails, the association of alpha-catenin and E-cadherin to beta-catenin is interdependent. Thus, binding of alpha-catenin to the N-tail, through conformational changes that affect the C-tail, facilitates the association of E-cadherin. These results indicate that different cofactors of beta-catenin bind coordinately to this protein and indicate how the two terminal ends of beta-catenin exquisitely modulate intermolecular binding within junctional complexes.     

Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

Background  

Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes) in physiological salt (0.14 M NaCl) at constant stoichiometry.     

The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains

A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples – Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) – and then combined results by meta‐analysis. DYX2 markers, specifically those in the 3′ untranslated region of DCDC2 (P = 1.43 × 10^?4), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic‐related genes ANKK1 (P = 1.02 × 10^?2) and DRD2 (P = 9.22 × 10^?3) and nicotinic‐related genes CHRNA3 (P = 2.51 × 10^?3) and BDNF (P = 8.14 × 10^?3) with case–control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language‐related outcomes remains to be elucidated.     

Sublethal effects of a rapidly spreading native alga on a key herbivore

1. Multiple anthropogenic stressors are causing a global decline in foundation species, including macrophytes, often resulting in the expansion of functionally different, more stressor‐tolerant macrophytes. Previously subdominant species may experience further positive demographic feedback if they are exposed to weaker plant–herbivore interactions, possibly via decreased palatability or being structurally different from the species they are replacing. However, the consequences of the spread of opportunistic macrophytes for the local distribution and life history of herbivores are unknown.
2. The green alga, Caulerpa filiformis, previously a subdominant macrophyte on low intertidal‐shallow subtidal rock shores, is becoming locally more abundant and has spread into warmer waters across the coast of New South Wales, Australia.
3. In this study, we measured (a) the distribution and abundance of a key consumer, the sea urchin Heliocidaris erythrogramma, across a seascape at sites where C. filiformis has become dominant, (b) performed behavioral field experiments to test the role of habitat selection in determining the local distribution of H. erythrogramma, and (c) consumer experiments to test differential palatability between previously dominant higher quality species like Ecklonia radiata and Sargassum sp. and C. filiformis and the physiological consequences of consuming it.
4. At all sites, urchin densities were positively correlated with distance away from C. filiformis beds, and they actively moved away from beds. Feeding experiments showed that, while urchins consumed C. filiformis, sometimes in equal amounts to higher quality algae, there were strong sublethal consequences associated with C. filiformis consumption, mainly on reproductive potential (gonad size). Specifically, the gonad size of urchins that fed on C. filiformis was equivalent to that in starved urchins. There was also a tendency for urchin mortality to be greater when fed C. filiformis.
5. Overall, strong negative effects on herbivore life‐history traits and potentially their survivorship may establish further positive feedback on C. filiformis abundance that contributes to its spread and may mediate shifts from top‐down to bottom‐up control at locations where C. filiformis has become dominant.

The spread of the previously subdominant Caulerpa filiformis along the coast of NSW, Australia has strong lethal and sublethal effects on a key herbivore population. We performed sea urchin surveys, behavioral experiments, and consumer experiments and found that C aulerpa has strong negative effects on their populations. These results may establish reinforcing feedbacks on the spreading algae and mediate shifts from top‐down to bottom‐up control.     

Discovery of a novel class of zwitterionic,potent, selective and orally active S1P1 direct agonists

Amido-1,3,4-thiadiazoles have been identified as a novel structural class of potent and selective sphingosine-1-phosphate receptor subtype 1 agonists. Starting from a micromolar HTS hit with the help of an in-house homology model, robust structural–activity relationships were developed to yield compounds with good selectivity and excellent in vivo efficacy in rat models.