The signature of competition in ecomorphological traits across the avian radiation

Competition for shared resources represents a fundamental driver of biological diversity. However, the tempo and mode of phenotypic evolution in deep-time has been predominantly investigated using trait evolutionary models which assume that lineages evolve independently from each other. Consequently, the role of species interactions in driving macroevolutionary dynamics remains poorly understood. Here, we quantify the prevalence for signatures of competition between related species in the evolution of ecomorphological traits across the bird radiation. We find that mechanistic trait models accounting for the effect of species interactions on phenotypic divergence provide the best fit for the data on at least one trait axis in 27 out of 59 clades ranging between 21 and 195 species. Where it occurs, the signature of competition generally coincides with positive species diversity-dependence, driven by the accumulation of lineages with similar ecologies, and we find scarce evidence for trait-dependent or negative diversity-dependent phenotypic evolution. Overall, our results suggest that the footprint of interspecific competition is often eroded in long-term patterns of phenotypic diversification, and that other selection pressures may predominantly shape ecomorphological diversity among extant species at macroevolutionary scales.     

Inactivation of Nitric Oxide by Uric Acid

The 1980 identification of nitric oxide (NO) as an endothelial cell-derived relaxing factor resulted in an unprecedented biomedical research of NO and established NO as one of the most important cardiovascular, nervous and immune system regulatory molecule. A reduction in endothelial cell NO levels leading to “endothelial dysfunction” has been identified as a key pathogenic event preceding the development of hypertension, metabolic syndrome, and cardiovascular disease. The reduction in endothelial NO in cardiovascular disease has been attributed to the action of oxidants that either directly react with NO or uncouple its substrate enzyme. In this report, we demonstrate that uric acid (UA), the most abundant antioxidant in plasma, reacts directly with NO in a rapid irreversible reaction resulting in the formation of 6-aminouracil and depletion of NO. We further show that this reaction occurs preferentially with NO even in the presence of oxidants peroxynitrite and hydrogen peroxide and that the reaction is at least partially blocked by glutathione. This study shows a potential mechanism by which UA may deplete NO and cause endothelial dysfunction, particularly under conditions of oxidative stress in which UA is elevated and intracellular glutathione is depleted.     

Synthesis,structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3?+?2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo- and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer.     

The impact of rate heterogeneity on inference of phylogenetic models of trait evolution

Rates of trait evolution are known to vary across phylogenies; however, standard evolutionary models assume a homogeneous process of trait change. These simple methods are widely applied in small‐scale phylogenetic studies, whereas models of rate heterogeneity are not, so the prevalence and patterns of potential rate variation in groups up to hundreds of species remain unclear. The extent to which trait evolution is modelled accurately on a given phylogeny is also largely unknown because studies typically lack absolute model fit tests. We investigated these issues by applying both rate‐static and variable‐rates methods on (i) body mass data for 88 avian clades of 10–318 species, and (ii) data simulated under a range of rate‐heterogeneity scenarios. Our results show that rate heterogeneity is present across small‐scaled avian clades, and consequently applying only standard single‐process models prompts inaccurate inferences about the generating evolutionary process. Specifically, these approaches underestimate rate variation, and systematically mislabel temporal trends in trait evolution. Conversely, variable‐rates approaches have superior relative fit (they are the best model) and absolute fit (they describe the data well). We show that rate changes such as single internal branch variations, rate decreases and early bursts are hard to detect, even by variable‐rates models. We also use recently developed absolute adequacy tests to highlight misleading conclusions based on relative fit alone (e.g. a consistent preference for constrained evolution when isolated terminal branch rate increases are present). This work highlights the potential for robust inferences about trait evolution when fitting flexible models in conjunction with tests for absolute model fit.     

Nitric oxide binding properties of neuroglobin. A characterization by EPR and flash photolysis

Neuroglobin is a recently discovered member of the globin superfamily. Combined electron paramagnetic resonance and optical measurements show that, in Escherichia coli cell cultures with low O(2) concentration overexpressing wild-type mouse recombinant neuroglobin, the heme protein is mainly in a hexacoordinated deoxy ferrous form (F8His-Fe(2+)-E7His), whereby for a small fraction of the protein the endogenous protein ligand is replaced by NO. Analogous studies for mutated neuroglobin (mutation of E7-His to Leu, Val, or Gln) reveal the predominant presence of the nitrosyl ferrous form. After sonication of the cells wild-type neuroglobin oxidizes rapidly to the hexacoordinated ferric form, whereas NO ligation initially protects the mutants from oxidation. Flash photolysis studies of wild-type neuroglobin and its E7 mutants show high recombination rates (k(on)) and low dissociation rates (k(off)) for NO, indicating a high intrinsic affinity for this ligand similar to that of other hemoglobins. Since the rate-limiting step in ligand combination with the deoxy-hexacoordinated wild-type form involves the dissociation of the protein ligand, NO binding is slower than for the related mutants. Structural and kinetic characteristics of neuroglobin and its mutants are analyzed. NO production in rapidly growing E. coli cell cultures is discussed.     

Dual Targeted Therapy with p53 siRNA and Epigallocatechingallate in a Triple Negative Breast Cancer Cell Model

Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG). RT²Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated) in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment.     

Aerobic capacity of Peruvian Quechua: A test of the developmental adaptation hypothesis

High altitude natives are reported to have outstanding work capacity in spite of the challenge of oxygen transport and delivery in hypoxia. To evaluate the developmental effect of lifelong exposure to hypoxia on aerobic capacity, VO_2peak was measured on two groups of Peruvian Quechua subjects (18–35 years), who differed in their developmental exposure to altitude. Male and female volunteers were recruited in Lima, Peru (150 m), and were divided in two groups, based on their developmental exposure to hypoxia, those: a) Born at sea‐level individuals (BSL), with no developmental exposure to hypoxia (n = 34) and b) Born at high‐altitude individuals (BHA) with full developmental exposure to hypoxia (n = 32), but who migrated to sea‐level as adults (>16‐years‐old). Tests were conducted both in normoxia (BP = 750 mm Hg) and normobaric hypoxia at sea‐level (BP = 750 mm Hg, FiO₂ = 0.12, equivalent to 4,449 m), after a 2‐month training period (in order to control for initial differences in physical fitness) at sea‐level. BHA had a significantly higher VO_2peak at hypoxia (40.31 ± 1.0 ml/min/kg) as compared to BSL (35.78 ± 0.96 ml/min/kg, P = 0.001), adjusting for sex. The decrease of VO_2peak at HA relative to SL (ΔVO_2peak) was not different between groups, controlling for baseline levels (VO_2peak at sea‐level) and sex (BHA = 0.35 ± 0.04 l/min, BSL = 0.44 ± 0.04 l/min; P = 0.12). Forced vital capacity (controlling for height) and the residuals of VO_2peak (controlling for weight) had a significant association in the BHA group only (r = 0.155; P = 0.031). In sum, results indicate that developmental exposure to altitude constitutes an important factor to determine superior exercise performance. Am J Phys Anthropol 156:363–373, 2015. © 2014 Wiley Periodicals, Inc.     

Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11beta-HSD1 in the Syrian hamster.

Recent findings indicate that elevated levels of glucocorticoids (GC), governed by the expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and GC receptors (GR), in visceral adipose tissue and skeletal muscle lead to increased insulin resistance and the metabolic syndrome. Paradoxically, evidence indicates that aerobic exercise attenuates the development of the metabolic syndrome even though it stimulates acute increases in circulating GC levels. To investigate the hypothesis that training alters peripheral GC action to maintain insulin sensitivity, young male hamsters were randomly divided into sedentary (S) and trained (T) groups (n = 8 in each). The T group had 24-h access to running wheels over 4 wk of study. In muscle, T hamsters had lower 11beta-HSD1 protein expression (19.2 +/- 1.40 vs. 22.2 +/- 0.96 optical density, P < 0.05), similar 11beta-HSD1 enzyme activity (0.9 +/- 0.27% vs. 1.1 +/- 0.26), and lower GR protein expression (9.7 +/- 1.86 vs. 15.1 +/- 1.78 optical density, P < 0.01) than S hamsters. In liver, 11beta-HSD1 protein expression tended to be lower in T compared with S (19.2 +/- 0.56 vs. 21.4 +/- 1.05, P = 0.07), whereas both enzyme activity and GR protein expression were similar. In contrast, visceral adipose tissue contained approximately 2.7-fold higher 11beta-HSD1 enzyme activity in T compared with S (12.9 +/- 3.3 vs. 4.8 +/- 1.5% conversion, P < 0.05) but was considerably smaller in mass (0.24 +/- 0.02 vs. 0.71 +/- 0.06 g). Thus the intracellular adaptation of GC regulators to exercise is tissue specific, resulting in decreases in GC action in skeletal muscle and increases in GC action in visceral fat. These adaptations may have important implications in explaining the protective effects of aerobic exercise on insulin resistance and other symptoms of the metabolic syndrome.