38 research outputs found

    Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.

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    The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to Wnt-β-catenin signaling and a promising therapeutic target in Wnt-dependent cancers. The pool of active β-catenin is normally limited by destruction complexes, whose assembly depends on the polymeric master scaffolding protein AXIN. Tankyrase, which poly(ADP-ribosyl)ates and thereby destabilizes AXIN, also can polymerize, but the relevance of these polymers has remained unclear. We report crystal structures of the polymerizing TNKS and TNKS2 sterile alpha motif (SAM) domains, revealing versatile head-to-tail interactions. Biochemical studies informed by these structures demonstrate that polymerization is required for Tankyrase to drive β-catenin-dependent transcription. We show that the polymeric state supports PARP activity and allows Tankyrase to effectively access destruction complexes through enabling avidity-dependent AXIN binding. This study provides an example for regulated signal transduction in non-membrane-enclosed compartments (signalosomes), and it points to novel potential strategies to inhibit Tankyrase function in oncogenic Wnt signaling

    Similar dispersal patterns between two closely related birds with contrasting migration strategies

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    Studying dispersal is crucial to understand metapopulation and sink-source dynamics and invasion processes. The capability to disperse is especially important for species living in fragmented habitats like wetlands. We investigated the distribution of natal and breeding dispersal distances and philopatry in Spanish populations of two closely related reedbed-nesting birds, the Moustached Warbler Acrocephalus melanopogon and the Eurasian Reed Warbler Acrocephalus scirpaceus. These warblers are morphologically very similar, but differ in migration strategy and, in our study area, in population size. Our aims were to find the best model for dispersal distances and to assess the occurrence of intra- or interspecific differences in dispersal patterns. We used ringing data from the Spanish marking scheme and selected recaptures to avoid including migrating individuals. In both species, most individuals were philopatric but dispersing birds were able to cross large distances (up to more than 100 km), suggesting the capability to compensate for habitat fragmentation. We found the heavy-tailed Cauchy distribution to be the best conceptual description for our data, in all cases but natal dispersal of Moustached Warblers. Among Eurasian Reed Warblers, natal philopatry was lower than breeding philopatry. We found no significant interspecific differences. This does not confirm the hypothesis of higher dispersal ability in long distance migrants (like Eurasian Reed Warblers) than in resident/short distance migrant bird species (like Moustached Warblers). The similarity in dispersal patterns among the two warblers may be explained by their close phylogenetic relatedness, similar constraints imposed on both species by a patchy habitat or similar evolutionary pressures.We are grateful to the many ringers who collected the data during years of fieldwork in Spain. Francesco Ceresa is supported by an "Atraent talent'' grant from the University of Valencia.Ceresa, F.; Belda, E.; Monrós González, JS. (2016). Similar dispersal patterns between two closely related birds with contrasting migration strategies. Population Ecology. 58(3):421-427. doi:10.1007/s10144-016-0547-0S421427583Banco de datos de anillamiento del remite ICONA – Ministerio de Medio Ambiente (2015) Datos de anillamiento y recuperaciones en España. Ministerio de Agricultura, Alimentación y Medio Ambiente, SEO/BirdLife, ICO, EBD-CSIC y GOB. Madrid (in Spanish)Begon M, Townsend CR, Harper JL (2006) Ecology: from individual to ecosystems, 4th edn. 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N. del Prat de Cabanes-Torreblanca. Doctoral thesis. University of Valencia, Valencia (in Spanish)Castany J, López G (2006) El carricerín real en España. I Censo Nacional (2005). SEO/BirdLife, Madrid (in Spanish with English abstract)Ceresa F, Belda EJ, Kvist L, Rguibi-Idrissi H, Monrós JS (2015) Does fragmentation of wetlands affect gene flow in sympatric Acrocephalus warblers with different migration strategies? J Avian Biol 46:577–588Cooper NW, Murphy MT, Redmond LJ, Dolan AC (2009) Density-dependent age at first reproduction in the eastern kingbird. Oikos 118:413–419Delignette-Muller ML, Dutang C (2015) fitdistrplus: An R Package for fitting distributions. J Stat Softw 64:1–34. http://www.jstatsoft.org/v64/i04/ . Accessed 2 Sep 2015Frankham R, Ballou JD, Briscoe DA (2010) Introduction to conservation genetics, 2nd edn. Cambridge University Press, CambridgeHengeveld R (1994) Small step invasion research. 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    Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

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    The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge

    Land Cover and Rainfall Interact to Shape Waterbird Community Composition

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    Human land cover can degrade estuaries directly through habitat loss and fragmentation or indirectly through nutrient inputs that reduce water quality. Strong precipitation events are occurring more frequently, causing greater hydrological connectivity between watersheds and estuaries. Nutrient enrichment and dissolved oxygen depletion that occur following these events are known to limit populations of benthic macroinvertebrates and commercially harvested species, but the consequences for top consumers such as birds remain largely unknown. We used non-metric multidimensional scaling (MDS) and structural equation modeling (SEM) to understand how land cover and annual variation in rainfall interact to shape waterbird community composition in Chesapeake Bay, USA. The MDS ordination indicated that urban subestuaries shifted from a mixed generalist-specialist community in 2002, a year of severe drought, to generalist-dominated community in 2003, of year of high rainfall. The SEM revealed that this change was concurrent with a sixfold increase in nitrate-N concentration in subestuaries. In the drought year of 2002, waterbird community composition depended only on the direct effect of urban development in watersheds. In the wet year of 2003, community composition depended both on this direct effect and on indirect effects associated with high nitrate-N inputs to northern parts of the Bay, particularly in urban subestuaries. Our findings suggest that increased runoff during periods of high rainfall can depress water quality enough to alter the composition of estuarine waterbird communities, and that this effect is compounded in subestuaries dominated by urban development. Estuarine restoration programs often chart progress by monitoring stressors and indicators, but rarely assess multivariate relationships among them. Estuarine management planning could be improved by tracking the structure of relationships among land cover, water quality, and waterbirds. Unraveling these complex relationships may help managers identify and mitigate ecological thresholds that occur with increasing human land cover

    Doñana. Acta vertebrata. vol 22 (1/2)

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    Relación entre el uso del espacio del mito (Aeghitalos caudatus) y la disponibilidad de artrópodos durante el periodo primavera-veranoHábitos frugívoros de la corzuela parda (Mazama gouazoubira, Ficher, 1814) (Mammalia: Cervidae), en un ambiente secundario de yungasComparación entre varias técnicas de estimación de la edad en zorros, Vulpes vulpes, de Doñana (sur de la Península Ibérica)Características morfológicas de los corzos (Capreolus capreolus) de las sierras de Cádiz-Málaga.Etograma y relación de la conducta con el hábitat y con la edad en el ñandú (Rhea americana)Variación estacional del área de campeo de Oxymycterus rufus (Rodentia: Cricetidae), en el delta del rio Paraná, ArgentinaTracking of a female american mink (Mustela vison, Schreber, 1777) in NE Spain.Nidificación de láridos en la provincia de Almeria (SE Ibérico)Expansión del área de distribución de Microtus arvalis asturianus Miller, 1908 (Rodentia, Arvicolidae) en la meseta norte (España)Diet of the thekla lark, Galerida theklae, in a shrubsteppe of southeastern SpainAlimentación de la lechuza campestre (Asio flammeus) en la submeseta norte (España), durante el periodo reproductorUso de cajas anidaderas por lirones grises (Glis glis) y ratones leonados (Apodemus flavicollis) en el norte de la Península Ibérica.Theoretical flight ranges of waders resting in the Ebro Delta during autumn migrationPeer reviewe

    Insights into collagen uptake by C-type mannose receptors from the crystal structure of Endo180 domains 1-4

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    SummaryThe C-type mannose receptor and its homolog Endo180 (or uPARAP, for urokinase plasminogen activator receptor-associated protein) mediate the endocytic uptake of collagen by macrophages and fibroblasts. This process is required for normal tissue remodeling, but also facilitates the growth and dissemination of tumors. We have determined the crystal structure at 2.5 Å resolution of the N-terminal region of Endo180, consisting of a ricin-like domain, a fibronectin type II (FN2) domain, and two C-type lectin (CTL) domains. The L-shaped arrangement of these domains creates a shallow trench spanning the FN2 and CTL1 domains, which was shown by mutagenesis to bind triple-helical and denatured collagen. Small-angle X-ray scattering showed that the L-shaped structure is maintained in solution at neutral and acidic pH, irrespective of calcium ion loading. Collagen binding was equally unaffected by acidic pH, suggesting that collagen release in endosomes is not regulated by changes within the Endo180 N-terminal region

    Functionality of chimeric TssA proteins in the type VI secretion system reveals sheath docking specificity within their N-terminal domains.

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    The genome of Pseudomonas aeruginosa encodes three type VI secretion systems, each comprising a dozen distinct proteins, which deliver toxins upon T6SS sheath contraction. The least conserved T6SS component, TssA, has variations in size which influence domain organisation and structure. Here we show that the TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation. We built chimeric TssA proteins by swapping C-termini and showed that these can be functional even when made of domains from different TssA sub-groups. Functional specificity requires the Nt1 domain, while the origin of the C-terminal domain is more permissive for T6SS function. We identify two regions in short TssA proteins, loop and hairpin, that contribute to sheath binding. We propose a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position
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