Factors limiting the establishment of canopy-forming algae on artificial structures

Macroalgal canopies are important ecosystem engineers, contributing to coastal productivity and supporting a rich assemblage of associated flora and fauna. However, they are often absent from infrastructures such as coastal defences and there has been a worldwide decline in their distribution in urbanised coastal areas. The macroalga Fucus spiralis is the only high-shore canopy forming species present in the Azores. It is widely distributed in the archipelago but is never found on coastal infrastructures. Here we evaluate factors that may potentially limit its establishment on artificial structures. A number of observational and manipulative experiments were used to test the hypotheses that: (i) limited-dispersal ability limits the colonisation of new plants onto artificial structures, (ii) vertical substratum slope negatively influences the survivorship of recruits, and (iii) vertical substratum slope also negatively influences the survivorship and fitness of adults. Results showed that the limited dispersal from adult plants may be a more important factor than slope in limiting the species ability to colonise coastal infrastructures, since the vertical substratum slope does not affect its fitness or survivorship.European Regional Development Fund (ERDF); COMPETE - Operational Competitiveness Programme; FCT - Foundation for Science and Technology; cE3c funding. GMM was supported by a postdoctoral grant awarded by FCT (SFRH/BDP/63040/2009). ACLP was funded by a FRCT research grant M3.1.5/F/098/2012. Support was also provided by CIRN/UAc (Centre of Natural Resources of University of the Azores).info:eu-repo/semantics/publishedVersio

Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS) in Mice Treated with FR91

One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC). However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis

Nowhere safe? Exploring the influence of urbanization across mainland and insular seashores in continental Portugal and the Azorean Archipelago

Differences in the structure and functioning of intensively urbanized vs. less human-affected systems are reported, but such evidence is available for amuch larger extent in terrestrial than in marine systems.Weexamined the hypotheses that (i) urbanization was associated to different patterns of variation of intertidal assemblages between urban and extra-urban environments; (ii) such patterns were consistent acrossmainland and insular systems, spatial scales from 10s cm to 100s km, and a three months period. Several trends emerged: (i) a more homogeneous distribution of most algal groups in the urban compared to the extra-urban condition and the opposite pattern of most invertebrates; (ii) smaller/larger variances of most organisms where these were, respectively, less/more abundant; (iii) largest variability of most response variables at small scale; (iv) no facilitation of invasive species by urbanization and larger cover of canopy-forming algae in the insular extra-urban condition. Present findings confirmthe acknowledged notion that futuremanagement strategieswill require to include representative assemblages and their relevant scales of variation associated to urbanization gradients on both the mainland and the islands

Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Human Molecular Genetics 22.16 (2013): 3296-3305 is available online at http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=23604518X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1(-) mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1(-) mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1(-) mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALDThis study was supported by grants from the European Commission (FP7-241622), the European Leukodystrophy Association (ELA2009-036C5; ELA2008-040C4), the Spanish Institute for Health Carlos III (FIS PI080991 and FIS PI11/01043), the Autonomous Government of Catalonia (2009SGR85) to A.P. and the Spanish Institute for Health Carlos III (Miguel Servet program CP11/00080) to S.F. The CIBER on Rare Diseases (CIBERER) is an initiative of the ISCIII. The study was developed under the COST action BM0604 (to A.P.). J.L.-E. was a fellow of the Department of Education, Universities and Research of the Basque Country Government (BFI07.126). S.F. was a fellow of the European Leukodystrophy Association (ELA 2010-020F1). The studies conducted at the Department of Experimental Medicine were supported in part by R&D grants from the Spanish Ministry of Science and Innovation (BFU2009-11879/BFI), the Spanish Ministry of Health (PI11/1532), the Autonomous Government of Catalonia (2009SGR735), the ‘La Caixa’ Foundation and COST B35 Action of the European Union. D.C. is a fellow from the Spanish Ministry of Health (FI08-00707). The studies conducted at the Department of Biochemistry and Molecular Biology, University of Barcelona, were supported by grants SAF2008-01896 and SAF2011-23636 from the Spanish Ministry of Science and Innovatio

Diversity and patterns of marine non‐native species in the archipelagos of Macaronesia

Aims The present study is the first attempt to grasp the scale and richness of marine biological invasions in Macaronesia. We pioneered a comprehensive non-native species (NNS), inventory in the region to determine their diversity patterns and native distribution origins. NNS were defined here as the result of both introductions and range expansions. We also used statistical modelling to examine relationships among NNS richness, anthropogenic activities, demographic and geographical variables across Macaronesia. Location Macaronesia. Methods A comprehensive literature search was conducted for marine NNS records in Macaronesia, registering the first record's location and year from 1884 to 2020. We used univariate and multivariate analyses to evaluate differences and similarities in community composition. By applying a Generalized Linear Model (GLM), we tested hypotheses regarding NNS richness as a function of anthropogenic activities, demographic and geographical variables. Results A total of 144 marine non-native species (NNS) were recorded for the whole of Macaronesia. The highest NNS richness was registered in the Canary Islands (76 NNS), followed by the Azores (66 NNS), Madeira (59 NNS) and finally Cabo Verde (18 NNS). Some differences amongst archipelagos were observed, such as the high number of non-native macroalgae in the Azores, fishes in the Canary Islands and tunicates in Cabo Verde. Overall, macroalgae, tunicates and bryozoans were the predominant taxonomic groups in the Macaronesian archipelagos. Madeira and Canary Islands were the archipelagos with more similarity in marine NNS, and Cabo Verde the most divergent. Finally, GLM suggested that non-native richness patterns across Macaronesia were dependent on the considered archipelago and strongly affected by (1) minimum distance to the mainland, (2) the total number of ports and marinas and (3) total marinas area (km2). Conclusions The model results and NNS listing in the present study will likely raise the awareness and response regarding marine NNS in the whole Macaronesia region, serving as a baseline for future research as well as implementing and enforcing regulations related to the introduction of marine NNS in oceanic islands

Heteroreceptor complexes formed by dopamine D1, histamine H3 and N-methyl-D-aspartate glutamate receptors as targets to prevent neuronal death in Alzheimer's disease

Alzheimer’s disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D , histamine H , and N-methylD-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by coimmunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H receptor agonists, via negative cross-talk, and H receptor antagonists, via cross-antagonism, decreased D receptor agonist signaling determined by ERK1/2 or Akt phosphorylation and counteracted D receptormediated excitotoxic cell death. Both D and H receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D -H receptor heteromer function. Likely due to heteromerization, H receptors act as allosteric regulator for D and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D or H receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D -H -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H receptor antagonists reduced NMDA or D receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H receptor antagonists reverted the toxicity induced by ß -amyloid peptide. Thus, histamine H receptors in D -H -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration

Structural Analysis of Prolyl Oligopeptidases Using Molecular Docking and Dynamics: Insights into Conformational Changes and Ligand Binding

Prolyl oligopeptidase (POP) is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana). Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD) simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases

Hypoxia-Induced Down-Regulation of Neprilysin by Histone Modification in Mouse Primary Cortical and Hippocampal Neurons

Amyloid β-peptide (Aβ) accumulation leads to neurodegeneration and Alzheimer's disease (AD). Aβ metabolism is a dynamic process in the Aβ production and clearance that requires neprilysin (NEP) and other enzymes to degrade Aβ. It has been reported that NEP expression is significantly decreased in the brain of AD patients. Previously we have documented hypoxia is a risk factor for Aβ generation in vivo and in vitro through increasing Aβ generation by altering β-cleavage and γ-cleavage of APP and down-regulating NEP, and causing tau hyperphosphorylation. Here, we investigated the molecular mechanisms of hypoxia-induced down-regulation of NEP. We found a significant decrease in NEP expression at the mRNA and protein levels after hypoxic treatment in mouse primary cortical and hippocampal neurons. Chromatin immunoprecipitation (ChIP) assays and relative quantitative PCR (q-PCR) revealed an increase of histone H3-lysine9 demethylation (H3K9me2) and a decrease of H3 acetylation (H3-Ace) in the NEP promoter regions following hypoxia. In addition, we found that hypoxia caused up-regulation of histone methyl transferase (HMT) G9a and histone deacetylases (HDACs) HDAC-1. Decreased expression of NEP during hypoxia can be prevented by application with the epigenetic regulators 5-Aza-2′-deoxycytidine (5-Aza), HDACs inhibitor sodium valproate (VA), and siRNA-mediated knockdown of G9a or HDAC1. DNA methylation PCR data do not support that hypoxia affects the methylation of NEP promoters. This study suggests that hypoxia may down-regulate NEP by increasing H3K9me2 and decreasing H3-Ace modulation