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•This is the first study on metals pollution in this Mediterranean Bay.•Environmental quality guidelines were used to assess the potential ecological risks.•The fractionation analysis ...of sediments showed the bioavailability of the metals.•Statistical analyses aided to better understanding of pollution sources.•Statistical analyses aided to localize the areas more polluted.
Concentrations of heavy metals were measured in sediment and water from Málaga Bay (South Spain). In the later twentieth century, cities such as Málaga, have suffered the impact of mass summer tourism. The ancient industrial activities, and the actual urbanization and coastal development, recreation and tourism, wastewaters treatment facilities, have been sources of marine pollution. In sediments, Ni was the most disturbing metal because Ni concentrations exceeded the effects range low (ERL), concentration at which toxicity could start to be observed in 85% of the samples analyzed. The metal bioavailability decreased in the order: Cd>Ni>Pb>Cu>Cr. In the sea water samples, Cd and Pb were the most disturbing metals because they exceeded the continuous criteria concentration (CCC) of US EPA in a 22.5% and 10.0% of the samples, respectively. Statistical analyses (ANOVA, PCA, CA) were performed.
Genome-wide association (GWA) studies offer the opportunity to identify genes that contribute to naturally occurring variation in quantitative traits. However, GWA relies exclusively on statistical ...association, so functional validation is necessary to make strong claims about gene function. We used a combination of gene-disruption platforms (Tnt1 retrotransposons, hairpin RNA-interference constructs, and CRISPR/Cas9 nucleases) together with randomized, well-replicated experiments to evaluate the function of genes that an earlier GWA study in Medicago truncatula had identified as candidates contributing to variation in the symbiosis between legumes and rhizobia. We evaluated ten candidate genes found in six clusters of strongly associated single nucleotide polymorphisms, selected on the basis of their strength of statistical association, proximity to annotated gene models, and root or nodule expression. We found statistically significant effects on nodule production for three candidate genes, each validated in two independent mutants. Annotated functions of these three genes suggest their contributions to quantitative variation in nodule production occur through processes not previously connected to nodulation, including phosphorous supply and salicylic acid-related defense response. These results demonstrate the utility of GWA combined with reverse mutagenesis technologies to discover and validate genes contributing to naturally occurring variation in quantitative traits. The results highlight the potential for GWA to complement forward genetics in identifying the genetic basis of ecologically and economically important traits.
Ongoing interest in the discovery of selective JAK3 inhibitors led us to design novel covalent inhibitors that engage the JAK3 residue Cys909 by cyanamide, a structurally and mechanistically ...differentiated electrophile from other cysteine reacting groups previously incorporated in JAK3 covalent inhibitors. Through crystallography, kinetic, and computational studies, interaction of cyanamide 12 with Cys909 was optimized leading to potent and selective JAK3 inhibitors as exemplified by 32. In relevant cell-based assays and in agreement with previous results from this group, 32 demonstrated that selective inhibition of JAK3 is sufficient to drive JAK1/JAK3-mediated cellular responses. The contribution from extrahepatic processes to the clearance of cyanamide-based covalent inhibitors was also characterized using metabolic and pharmacokinetic data for 12. This work also gave key insights into a productive approach to decrease glutathione/glutathione S-transferase-mediated clearance, a challenge typically encountered during the discovery of covalent kinase inhibitors.
We probe the merging channel of massive galaxies over the z = 0.3–1.3 redshift window by studying close pairs in a sample of 238 galaxies with stellar mass ≳1011 M⊙, from the SHARDS (Survey for ...High-z Absorption Red and Dead Sources) survey. SHARDS provides medium-band photometry equivalent to low-resolution optical spectra (R ∼ 50), allowing us to obtain extremely accurate photometric redshifts (median |Δz|/(1 + z) ∼ 0.55 per cent) and to improve the constraints on the age distribution of the stellar populations. Our data set is volume limited, probing merger progenitors with mass ratios 1:100 (μ ≡ M
sat/M
cen = 0.01) out to z = 1.3. A strong correlation is found between the age difference of host and companion galaxy and stellar mass ratio, from negligible age differences in major mergers to age differences ∼4 Gyr for 1:100 minor mergers. However, this correlation is simply a reflection of the mass–age trend in the general population. The dominant contributor to the growth of massive galaxies corresponds to mass ratios μ ≳ 0.3, followed by a decrease in the fractional mass growth rate linearly proportional to log μ, at least down to μ ∼ 0.01, suggesting a decreasing role of mergers involving low-mass companions, especially if dynamical friction time-scales are taken into account. A simple model results in an upper limit for the average mass growth rate of massive galaxies of (ΔM/M)/Δt ∼ 0.08 ± 0.02 Gyr−1, over the z ≲ 1 range, with an ∼70 per cent fractional contribution from (major) mergers with μ ≳ 0.3. The majority of the stellar mass contributed by mergers does not introduce significantly younger populations, in agreement with the small radial age gradients observed in present-day early-type galaxies.
Extremely compact massive galaxies at z ∼ 1.4 Trujillo, I.; Feulner, G.; Goranova, Y. ...
Monthly notices of the Royal Astronomical Society,
November 2006, Letnik:
373, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The optical rest-frame sizes of 10 of the most massive (∼5 × 1011 h−270 M⊙) galaxies found in the near-infrared MUNICS survey at 1.2 < z < 1.7 are analysed. Sizes are estimated in both the J and K′ ...filters. These massive galaxies are at least a factor of 4+1.9−1.0 (±1σ) smaller in the rest-frame V-band than local counterparts of the same stellar mass. Consequently, the stellar mass density of these objects is (at least) 60 times larger than that of massive ellipticals today. Although the stellar populations of these objects are passively fading, their structural properties are rapidly changing since that redshift. This observational fact disagrees with a scenario where the more massive and passive galaxies are fully assembled at z∼ 1.4 (i.e. a monolithic scenario) and points towards a dry merger scenario as the responsible mechanism for the subsequent evolution of these galaxies.
Abstract Objectives To describe uptake of breast and cervical cancer screening by women living in Spain, analyse the possible associated social and health factors, and compare uptake rates with those ...obtained in previous surveys. Study design Cross-sectional study using data from the 2011 Spanish national health survey. Methods Uptake of breast cancer screening was analysed by asking women aged 40–69 years whether they had undergone mammography in the previous two years. Uptake of cervical cancer screening was analysed by asking women aged 25–65 years whether they had undergone cervical cytology in the previous three years. Independent variables included sociodemographic characteristics, and variables related to health status and lifestyle. Results Seventy-two percent of women had undergone mammography in the previous two years. Having private health insurance increased the probability of breast screening uptake four-fold odds ratio (OR) 3.96, 95% confidence interval (CI) 2.71–5.79, and being an immigrant was a negative predictor for breast screening uptake. Seventy percent of women had undergone cervical cytology in the previous three years. Higher-educated women were more likely to have undergone cervical cancer screening (OR 2.59, 95% CI 1.97–3.40), and obese women and women living in rural areas were less likely to have undergone cervical cancer screening. There have been no relevant improvements in uptake rates of either breast or cervical cancer screening since 2006. Conclusion Uptake of breast and cervical cancer screening could be improved in Spain, and uptake rates have stagnated over recent years. Social disparities have been detected with regard to access to these screening tests, indicating that it is necessary to continue researching and optimizing prevention programmes in order to improve uptake and reduce these disparities.
Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clinical development and two FDA approved NMEs. However, despite significant ...effort during the past 2 decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within our research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which achieves JAK isoform specificity through covalent interaction with a unique JAK3 residue Cys-909. The relatively rapid resynthesis rate of the JAK3 enzyme presented a unique challenge in the design of covalent inhibitors with appropriate pharmacodynamics properties coupled with limited unwanted off-target reactivity. This effort resulted in the identification of 11 (PF-06651600), a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this JAK3-specific inhibitor 11 led to its evaluation in several human clinical studies.
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