Lactuca capensis reverses memory deficits in Aβ1‐42‐induced an animal model of Alzheimer's disease

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid‐β1‐42 (Aβ1‐42). Behavioural assays such as Y‐maze and radial arm maze test were used for assessing memory performance. Aβ1‐42 decreased cognitive performance in the behavioural tests which were ameliorated by pre‐treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1‐42 treatment while these deficits were recovered by pre‐treatment with the methanolic extract. In addition, rats were given Aβ1‐42 exhibited in the hippocampus decreased brain‐derived neurotrophic factor (BDNF) mRNA copy number and increased IL‐1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.     

Large‐scale disturbance legacies and the climate sensitivity of primary Picea abies forests

Determining the drivers of shifting forest disturbance rates remains a pressing global change issue. Large‐scale forest dynamics are commonly assumed to be climate driven, but appropriately scaled disturbance histories are rarely available to assess how disturbance legacies alter subsequent disturbance rates and the climate sensitivity of disturbance. We compiled multiple tree ring‐based disturbance histories from primary Picea abies forest fragments distributed throughout five European landscapes spanning the Bohemian Forest and the Carpathian Mountains. The regional chronology includes 11,595 tree cores, with ring dates spanning the years 1750–2000, collected from 560 inventory plots in 37 stands distributed across a 1,000 km geographic gradient, amounting to the largest disturbance chronology yet constructed in Europe. Decadal disturbance rates varied significantly through time and declined after 1920, resulting in widespread increases in canopy tree age. Approximately 75% of current canopy area recruited prior to 1900. Long‐term disturbance patterns were compared to an historical drought reconstruction, and further linked to spatial variation in stand structure and contemporary disturbance patterns derived from LANDSAT imagery. Historically, decadal Palmer drought severity index minima corresponded to higher rates of canopy removal. The severity of contemporary disturbances increased with each stand's estimated time since last major disturbance, increased with mean diameter, and declined with increasing within‐stand structural variability. Reconstructed spatial patterns suggest that high small‐scale structural variability has historically acted to reduce large‐scale susceptibility and climate sensitivity of disturbance. Reduced disturbance rates since 1920, a potential legacy of high 19th century disturbance rates, have contributed to a recent region‐wide increase in disturbance susceptibility. Increasingly common high‐severity disturbances throughout primary Picea forests of Central Europe should be reinterpreted in light of both legacy effects (resulting in increased susceptibility) and climate change (resulting in increased exposure to extreme events).     

In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein kinase.

Controlled expression of cellular and viral genes through alternative precursor messenger RNA (pre-mRNA) splicing requires serine/arginine-rich (SR) proteins. The Clk1 kinase, which phosphorylates SR proteins, is regulated through alternative splicing of the Clk1 pre-mRNA, yielding mRNAs encoding catalytically active and truncated inactive polypeptides (Clk1 and Clk1T, respectively). We present evidence that Clk1 and Clk1T proteins regulate the splicing of Clk1 and adenovirus pre-mRNAs in vivo. The peptide domain encoded by the alternatively spliced exon of Clk1 is essential for the regulatory activity of the Clk1 kinase. This is the first direct demonstration of an in vivo link between alternative splicing and protein kinase activity.     

A realistic in silico model for structure/function studies of molybdenum–copper CO dehydrogenase

CO dehydrogenase (CODH) is an environmentally crucial bacterial enzyme that oxidizes CO to CO₂ at a Mo–Cu active site. Despite the close to atomic resolution structure (1.1 Å), significant uncertainties have remained with regard to the protonation state of the water-derived equatorial ligand coordinated at the Mo-center, as well as the nature of intermediates formed during the catalytic cycle. To address the protonation state of the equatorial ligand, we have developed a realistic in silico QM model (~179 atoms) containing structurally essential residues surrounding the active site. Using our QM model, we examined each plausible combination of redox states (Mo^VI–Cu^I, Mo^V–Cu^II, Mo^V–Cu^I, and Mo^IV–Cu^I) and Mo-coordinated equatorial ligands (O^2?, OH^?, H₂O), as well as the effects of second-sphere residues surrounding the active site. Herein, we present a refined computational model for the Mo(VI) state in which Glu763 acts as an active site base, leading to a MoO₂-like core and a protonated Glu763. Calculated structural and spectroscopic data (hyperfine couplings) are in support of a MoO₂-like core in agreement with XRD data. The calculated two-electron reduction potential (E = ?467 mV vs. SHE) is in reasonable agreement with the experimental value (E = ?558 mV vs. SHE) for the redox couple comprising an equatorial oxo ligand and protonated Glu763 in the Mo^VI–Cu^I state and an equatorial water in the Mo^IV–Cu^I state. We also suggest a potential role of second-sphere residues (e.g., Glu763, Phe390) based on geometric changes observed upon exclusion of these residues in the most plausible oxidized states.     

Structural basis for the photochemistry of alpha-phycoerythrocyanin

Phycobiliproteins and phytochromes are light-harvesting and light-sensing proteins containing linear tetrapyrroles, so-called bile chromophores. The chromophores in certain biliproteins, including the phytochromes, isomerize reversibly from a stable Z-configuration to a stable E-configuration when irradiated with light of the appropriate wavelength. Here, we report the crystal structure of alpha-phycoerythrocyanin with its chromophore in the E-configuration, compare it with the Z-configuration found in trimeric phycoerythrocyanin, and reveal the structural bases of the isomerization. The geometric changes of the chromophore account for the large spectral shift, which characterizes the overall transition. Interactions of the chromophore A and D pyrrole rings with flexible protein moieties are required for the formation and stabilization of the isomers. We predict that the results will hold for all photoactive biliproteins.     

Ecological significance of extracellular vesicles in modulating host-virus interactions during algal blooms

Extracellular vesicles are produced by organisms from all kingdoms and serve a myriad of functions, many of which involve cell-cell signaling, especially during stress conditions and host-pathogen interactions. In the marine environment, communication between microorganisms can shape trophic level interactions and population succession, yet we know very little about the involvement of vesicles in these processes. In a previous study, we showed that vesicles produced during viral infection by the ecologically important model alga Emiliania huxleyi, could act as a pro-viral signal, by expediting infection and enhancing the half-life of the virus in the extracellular milieu. Here, we expand our laboratory findings and show the effect of vesicles on natural populations of E. huxleyi in a mesocosm setting. We profile the small-RNA (sRNA) cargo of vesicles that were produced by E. huxleyi during bloom succession, and show that vesicles applied to natural assemblages expedite viral infection and prolong the half-life of this major mortality agent of E. huxleyi. We subsequently reveal that exposure of the natural assemblage to E. huxleyi-derived vesicles modulates not only host-virus dynamics, but also other components of the microbial food webs, thus emphasizing the importance of extracellular vesicles to microbial interactions in the marine environment.Subject terms: Virus-host interactions, Microbial ecology, Water microbiology     

Genomics of adaptive divergence with chromosome‐scale heterogeneity in crossover rate

Genetic differentiation between divergent populations is often greater in chromosome centres than peripheries. Commonly overlooked, this broadscale differentiation pattern is sometimes ascribed to heterogeneity in crossover rate and hence linked selection within chromosomes, but the underlying mechanisms remain incompletely understood. A literature survey across 46 organisms reveals that most eukaryotes indeed exhibit a reduced crossover rate in chromosome centres relative to the peripheries. Using simulations of populations diverging into ecologically different habitats through sorting of standing genetic variation, we demonstrate that such chromosome‐scale heterogeneity in crossover rate, combined with polygenic divergent selection, causes stronger hitchhiking and especially barriers to gene flow across chromosome centres. Without requiring selection on new mutations, this rapidly leads to elevated population differentiation in the low‐crossover centres relative to the high‐crossover peripheries of chromosomes (“Chromosome Centre‐Biased Differentiation”, CCBD). Using simulated and empirical data, we then show that strong CCBD between populations can provide evidence of polygenic adaptive divergence with a phase of gene flow. We further demonstrate that chromosome‐scale heterogeneity in crossover rate impacts analyses beyond that of population differentiation, including the inference of phylogenies and parallel adaptive evolution among populations, the detection of genetic loci under selection, and the interpretation of the strength of selection on genomic regions. Overall, our results call for a greater appreciation of chromosome‐scale heterogeneity in crossover rate in evolutionary genomics.