223 research outputs found

    Network 'small-world-ness': a quantitative method for determining canonical network equivalence

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    Background: Many technological, biological, social, and information networks fall into the broad class of 'small-world' networks: they have tightly interconnected clusters of nodes, and a shortest mean path length that is similar to a matched random graph (same number of nodes and edges). This semi-quantitative definition leads to a categorical distinction ('small/not-small') rather than a quantitative, continuous grading of networks, and can lead to uncertainty about a network's small-world status. Moreover, systems described by small-world networks are often studied using an equivalent canonical network model-the Watts-Strogatz (WS) model. However, the process of establishing an equivalent WS model is imprecise and there is a pressing need to discover ways in which this equivalence may be quantified. Methodology/Principal Findings: We defined a precise measure of 'small-world-ness' S based on the trade off between high local clustering and short path length. A network is now deemed a 'small-world' if S. 1-an assertion which may be tested statistically. We then examined the behavior of S on a large data-set of real-world systems. We found that all these systems were linked by a linear relationship between their S values and the network size n. Moreover, we show a method for assigning a unique Watts-Strogatz (WS) model to any real-world network, and show analytically that the WS models associated with our sample of networks also show linearity between S and n. Linearity between S and n is not, however, inevitable, and neither is S maximal for an arbitrary network of given size. Linearity may, however, be explained by a common limiting growth process. Conclusions/Significance: We have shown how the notion of a small-world network may be quantified. Several key properties of the metric are described and the use of WS canonical models is placed on a more secure footing

    High occurrence of giardiasis in children living on a 'landless farm workers' settlement in Araras, São Paulo, Brazil

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    Enteric parasitosis remains an important public health problem in many areas around the world including in Brazil, and it is frequently associated with poverty and lack of sanitation facilities. Research carried out over the course of a year revealed that 96.6% (28/29) of children randomly selected from a 'landless farm workers' settlement in Araras, São Paulo, aged 4 - 15 years, presented Giardia intestinalis cysts. After referral to the neighborhood Health Office, all the children received tinidazole, given as a single dose of 50 mg/kg and 12 months later, new fecal samples were collected and analyzed. Despite the low adherence to the study, a high percentage (64.3% - 9/14) of the children remained positive for the parasite. This study showed a high positivity of giardiasis in child residents of the settlement, even after treatment; adults were not sensitized to the study and did not collected and/or deliver children fecal samples. The precarious living conditions are consistent with a high susceptibility to parasitic diseases, suggesting that the treatment of the infected individuals without identifying and eradicating the means of contamination is simply a palliative measure

    Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

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    Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.Howard Hughes Medical InstituteFRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.

    Assessing the congruence of thermal niche estimations derived from distribution and physiological data. A test using diving beetles.

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    A basic aim of ecology is to understand the determinants of organismal distribution, the niche concept and species distribution models providing key frameworks to approach the problem. As temperature is one of the most important factors affecting species distribution, the estimation of thermal limits is crucially important for inferring range constraints. It is expectable that thermal physiology data derived from laboratory experiments and species' occurrences may express different aspects of the species' niche. However, there is no study systematically testing this prediction in a given taxonomic group while controlling by potential phylogenetic inertia. We estimate the thermal niches of twelve Palaearctic diving beetles species using physiological data derived from experimental analyses in order to examine the extent to which these coincided with those estimated from distribution models based on observed occurrences. We found that thermal niche estimates derived from both approaches lack general congruence, and these results were similar before and after controlling by phylogeny. The congruence between potential distributions obtained from the two different procedures was also explored, and we found again that the percentage of agreement were not very high (~60%). We confirm that both thermal niche estimates derived from geographical and physiological data are likely to misrepresent the true range of climatic variation that these diving beetles are able to tolerate, and so these procedures could be considered as incomplete but complementary estimations of an inaccessible reality

    Normal growth and development in mice over-expressing the CCN family member WISP3

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    Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the Wisp3 knockout mice has constrained studies of the protein’s in vivo function. Over-expression experiments in zebrafish indicated that WISP3 may function as a BMP and Wnt signaling modulator. To determine whether these biologic activities are retained in mice, we created two strains of transgenic mice that over-express WISP3 in a broad array of tissues. Despite strong and persistent protein over-expression, the transgenic mice remained phenotypically indistinguishable from their non-transgenic littermates. Surprisingly, WISP3 contained in conditioned medium recovered from transgenic mouse primary kidney cell cultures was able to bind BMP and to inhibit BMP signaling in vitro. Factors that account for the difference between the in vitro and in vivo activities of WISP3 remain unknown. At present, the mouse remains a challenging model organism in which to explore the biologic function of WISP3

    Contribution of spatially explicit models to climate change adaptation and mitigation plans for a priority forest habitat

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    Climate change will impact forest ecosystems, their biodiversity and the livelihoods they sustain. Several adaptation and mitigation strategies to counteract climate change impacts have been proposed for these ecosystems. However, effective implementation of such strategies requires a clear understanding of how climate change will influence the future distribution of forest ecosystems. This study uses maximum entropy modelling (MaxEnt) to predict environmentally suitable areas for cork oak (Quercus suber) woodlands, a socio-economically important forest ecosystem protected by the European Union Habitats Directive. Specifically, we use two climate change scenarios to predict changes in environmental suitability across the entire geographical range of the cork oak and in areas where stands were recently established. Up to 40 % of current environmentally suitable areas for cork oak may be lost by 2070, mainly in northern Africa and southern Iberian Peninsula. Almost 90 % of new cork oak stands are predicted to lose suitability by the end of the century, but future plantations can take advantage of increasing suitability in northern Iberian Peninsula and France. The predicted impacts cross-country borders, showing that a multinational strategy, will be required for cork oak woodland adaptation to climate change. Such a strategy must be regionally adjusted, featuring the protection of refugia sites in southern areas and stimulating sustainable forest management in areas that will keep long-term suitability. Afforestation efforts should also be promoted but must consider environmental suitability and land competition issues

    Evolutionary diversity is associated with wood productivity in Amazonian forests

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    Higher levels of taxonomic and evolutionary diversity are expected to maximize ecosystem function, yet their relative importance in driving variation in ecosystem function at large scales in diverse forests is unknown. Using 90 inventory plots across intact, lowland, terra firme, Amazonian forests and a new phylogeny including 526 angiosperm genera, we investigated the association between taxonomic and evolutionary metrics of diversity and two key measures of ecosystem function: aboveground wood productivity and biomass storage. While taxonomic and phylogenetic diversity were not important predictors of variation in biomass, both emerged as independent predictors of wood productivity. Amazon forests that contain greater evolutionary diversity and a higher proportion of rare species have higher productivity. While climatic and edaphic variables are together the strongest predictors of productivity, our results show that the evolutionary diversity of tree species in diverse forest stands also influences productivity. As our models accounted for wood density and tree size, they also suggest that additional, unstudied, evolutionarily correlated traits have significant effects on ecosystem function in tropical forests. Overall, our pan-Amazonian analysis shows that greater phylogenetic diversity translates into higher levels of ecosystem function: tropical forest communities with more distantly related taxa have greater wood productivity

    Lack of interaction between ErbB2 and insulin receptor substrate signaling in breast cancer

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    BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models. METHODS: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTV-IRS2 bigenic mice. Signaling crosstalk between ErbB2 and IRSs was examined in vitro by knockdown or overexpression followed by western blot analysis for downstream signaling intermediates and growth assays. RESULTS: A cross between MMTV-ErbB2 and MMTV-IRS2 mice demonstrated no enhancement of ErbB2 mediated mammary tumorigenesis or metastasis by elevated IRS2. Substantiating this, overexpression or knockdown of IRS1 or IRS2 in MMTV-ErbB2 mammary cancer cell lines had little effect upon ErbB2 signaling. Similar results were obtained in human mammary epithelial cells (MCF10A) and breast cancer cell lines. CONCLUSION: Despite previous evidence suggesting that ErbB receptors can bind and activate IRSs, our findings indicate that ErbB2 does not cooperate with the IRS pathway in these models to promote mammary tumorigenesis
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