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M. José Feito Mercedes Jiménez Concha Fernández-Cabrera Germán Rivas Guillermo Giménez-Gallego Rosa M. Lozano 《Analytical biochemistry》2011,411(1):1
Here we describe, for the first time, the design and characterization of a bona fide fluorescently labeled mutant of the human acidic fibroblast growth factor (aFGF). The aFGF–Cys2 mutant was recombinantly synthesized by substituting the second amino acid with a reactive cysteine whose sulfhydryl group’s side chain reactivity facilitated the covalent binding of a fluorescent probe as a thiolyte monobromobimane. Using a combination of biophysical and functional assays, we found that the fluorescently labeled mutant aFGF is characterized by essentially the same global folding, mitogenic activity, and association behavior with heparin, its physiological activator, as the unlabeled wild-type protein. We used this new tracer protein mutant to determine the association behavior of aFGF with heparin in the presence of high concentrations of albumin that mimicked more closely the plasma medium in which aFGF is naturally located and in which it has evolved to function. By exposing the aFGF–Cys2–heparin complex to increasing concentrations of albumin up to physiological plasma levels, we were able to demonstrate that macromolecular crowding does not affect the stoichiometry of the interaction. In summary, the dimeric aFGF–Cys2–heparin complex might represent a biologically relevant complex in physiological media. 相似文献
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Juan Ignacio Ruiz Kaamel Nuhu Justin Tyler McDaniel Federico Popoff Ariel Izcovich Juan Martin Criniti 《PloS one》2015,10(10)
Background
Maternal and infant mortality are highly devastating, yet, in many cases, preventable events for a community. The human development of a country is a strong predictor of maternal and infant mortality, reflecting the importance of socioeconomic factors in determinants of health. Previous research has shown that the Human Development Index (HDI) predicts infant mortality rate (IMR) and the maternal mortality ratio (MMR). Inequality has also been shown to be associated with worse health in certain populations. The main purpose of the present study was to determine the correlation and predictive power of the Inequality Adjusted Human Development Index (IHDI) as a measure of inequality with the Infant Mortality Rate (IMR), Maternal Mortality Rate (MMR), Early Neonatal Mortality Rate (ENMR), Late Neonatal Mortality Rate (LNMR), and the Post Neonatal Mortality Rate (PNMR).Methods and Findings
Data for the present study were downloaded from two sources: infant and maternal mortality data were downloaded from the Global Burden of Disease 2013 Cause of Death Database and the Human Development Index (HDI) and Inequality-Adjusted Human Development Index (IHDI) data were downloaded from the United Nations Development Program (UNDP). Pearson correlation coefficients were estimated, following logarithmic transformations to the data, to examine the relationship between HDI and IHDI with MMR, IMR, ENMR, LNMR, and PNMR. Steiger’s Z test for the equality of two dependent correlations was utilized in order to determine whether the HDI or IHDI was more strongly associated with the outcome variables. Lastly, we constructed OLS regression models in order to determine the predictive power of the HDI and IHDI in terms of the MMR, IMR, ENMR, LNMR, and PNMR.Maternal and infant mortality were both strongly and negatively correlated with both HDI and IHDI; however, Steiger’s Z test for the equality of two dependent correlations revealed that IHDI was more strongly correlated than HDI with MMR (Z = 4.897, p < 0.001), IMR (Z = 2.524, p = 0.012), ENMR (Z = 2.936, p = 0.003), LNMR (Z = 2.272, p = 0.023), and PNMR (Z = 2.277, p = 0.023). Furthermore, side-by-side OLS regression models revealed that, when IHDI was used as the predictor variable instead of HDI, the R 2 value was 0.053 higher for MMR, 0.025 higher for IMR, 0.038 higher for ENMR, 0.029 higher for LNMR, and 0.026 higher for PNMR.Conclusions
Even when both the HDI and the IHDI correlate with the infant and maternal mortality rates, the IHDI is a better predictor for these two health indicators. Therefore, these results add more evidence that inequality is playing an important role in determining the health status of various populations in the world and more efforts should be put into programs to fight inequality. 相似文献15.
Giraud A Arous S De Paepe M Gaboriau-Routhiau V Bambou JC Rakotobe S Lindner AB Taddei F Cerf-Bensussan N 《PLoS genetics》2008,4(1):e2
While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments. 相似文献
16.
lvaro Dugo‐Cota Carles Vil Ariel Rodríguez Alejandro Gonzalez‐Voyer 《Ecology letters》2019,22(5):884-893
Replicate radiations, the repeated multiplication of species associated with ecological divergence, have attracted much attention and generated as much debate. Due to the few well‐studied cases, it remains unclear whether replicate radiations are an exceptional result of evolution or a relatively common example of the power of adaptation by natural selection. We examined the case of Eleutherodactylus frogs, which radiated in the Caribbean islands resulting in more than 160 species that occupy very diverse habitats. A time‐calibrated phylogeny revealed that these frogs independently diversified on all larger islands producing species that occupy a broad range of microhabitats in different islands. Using phylogenetic comparative methods, we found an association between morphological traits and particular microhabitats, and for most microhabitats detected significant morphological convergence. Our results indicate Caribbean Eleutherodactylus are a novel example of replicate radiations, and highlight the predictability of evolutionary processes, as similar ecological opportunities can lead to similar outcomes. 相似文献
17.
Background
To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke. 相似文献18.
19.
Methods for quantitative characterization of heterologous protein-protein interactions by means of analytical ultracentrifugation (AUC) include sedimentation equilibrium, tracer sedimentation equilibrium, sedimentation velocity, and analytical band sedimentation. Fundamental principles governing the behavior of macromolecules in a centrifugal field are summarized, and the application of these principles to the interpretation of data obtained from each type of experiment is reviewed. Instrumentation and software for the acquisition and analysis of data obtained from different types of AUC experiments are described. 相似文献
20.
Pura Díaz-Veiga Mayte Sancho Álvaro García Esther Rivas Elixabet Abad Nerea Suárez Gabriela Mondragón Cristina Buiza Ana Orbegozo Javier Yanguas 《Revista espa?ola de geriatría y gerontología》2014