Immune and Stress Responses Covary with Melanin-Based Coloration in the Barn Swallow

Eumelanin and pheomelanin are the main endogenous pigments in animals and melanin-based coloration has multiple functions. Melanization is associated with major life-history traits, including immune and stress response, possibly because of pleiotropic effects of genes that control melanogenesis. The net effects on pheo- versus eumelanization and other life-history traits may depend on the antagonistic effects of the genes that trigger the biosynthesis of either melanin form. Covariation between melanin-based pigmentation and fitness traits enforced by pleiotropic genes has major evolutionary implications particularly for socio-sexual communication. However, evidence from non-model organisms in the wild is limited to very few species. Here, we tested the hypothesis that melanin-based coloration of barn swallow (Hirundo rustica) throat and belly feathers covaries with acquired immunity and activation of the hypothalamic–pituitary–adrenal (HPA) axis, as gauged by corticosterone plasma levels. Individuals of both sexes with darker brownish belly feathers had weaker humoral immune response, while darker males had higher circulating corticosterone levels only when parental workload was experimentally reduced. Because color of belly feathers depends on both eu- and pheomelanin, and its darkness decreases with an increase in the concentration of eu- relative to pheomelanin, these results are consistent with our expectation that relatively more eu- than pheomelanized individuals have better immune response and smaller activation of the HPA-axis. Covariation of immune and stress response arose for belly but not throat feather color, suggesting that any function of color as a signal of individual quality or of alternative life-history strategies depends on plumage region.     

DEFENSE TRAITS OF LARVAL DROSOPHILA MELANOGASTER EXHIBIT GENETICALLY BASED TRADE‐OFFS AGAINST DIFFERENT SPECIES OF PARASITOIDS

Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species‐specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade‐offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade‐off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade‐off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits.     

The extremo-α-carbonic anhydrase (CA) from Sulfurihydrogenibium azorense,the fastest CA known,is highly activated by amino acids and amines

The α-carbonic anhydrase (CA, EC 4.2.1.1) from the extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) was recently shown to be the fastest CA known. Here we investigated this enzyme for its activation with a series of amino acids and amines. The best SazCA activators were d-Phe, l-DOPA, l- and d-Trp, dopamine and serotonin, which showed activation constants in the range of 3–23 nM. l- and d-His, l-Phe, l-Tyr, 2-pyridyl-methylamine and L-adrenaline were also effective activators (K_As in the range of 62–90 nM), whereas d-Dopa, d-Tyr and several heterocyclic amines showed activity in the micromolar range. The good thermal stability, robustness, very high catalytic activity and propensity to be activated by simple amino acids and amines, make SazCA a very interesting candidate for biomimetic CO₂ capture processes.     

A highly catalytically active γ-carbonic anhydrase from the pathogenic anaerobe Porphyromonas gingivalis and its inhibition profile with anions and small molecules

Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the γ-class are present in archaea, bacteria and plants but, except the Methanosarcina thermophila enzymes CAM and CAMH, they were poorly characterized so far. Here we report a new such enzyme (PgiCA), the γ-CA from the oral cavity pathogenic bacterium Porphyromonas gingivalis, the main causative agent of periodontitis. PgiCA showed a good catalytic activity for the CO₂ hydration reaction, comparable to that of the human (h) isoform hCA I. Inorganic anions such as thiocyanate, cyanide, azide, hydrogen sulfide, sulfamate and trithiocarbonate were effective PgiCA inhibitors with inhibition constants in the range of 41–97 μM. Other effective inhibitors were diethyldithiocarbamate, sulfamide, and phenylboronic acid, with K_Is of 4.0–9.8 μM. The role of this enzyme as a possible virulence factor of P. gingivalis is poorly understood at the moment but its good catalytic activity and the possibility to be inhibited by a large number of compounds may lead to interesting developments in the field.     

Nucleophosmin mutations in acute myeloid leukemia: A tale of protein unfolding and mislocalization

Nucleophosmin (NPM1) is an abundant, ubiquitously expressed protein mainly localized at nucleoli but continuously shuttling between nucleus and cytoplasm. NPM1 plays a role in several cellular functions, including ribosome biogenesis and export, centrosome duplication, chromatin remodeling, DNA repair, and response to stress stimuli. Much of the interest in this protein arises from its relevance in human malignancies. NPM1 is frequently overexpressed in solid tumors and is the target of several chromosomal translocations in hematologic neoplasms. Notably, NPM1 has been characterized as the most frequently mutated gene in acute myeloid leukemia (AML). Mutations alter the C‐terminal DNA‐binding domain of the protein and result in its aberrant nuclear export and stable cytosolic localization. In this review, we focus on the leukemia‐associated NPM1 C‐terminal domain and describe its structure, function, and the effect exerted by leukemic mutations. Finally, we discuss the possibility to target NPM1 for the treatment of cancer and, in particular, of AML patients with mutated NPM1 gene.     

Population genomics from pool sequencing

Next generation sequencing of pooled samples is an effective approach for studies of variability and differentiation in populations. In this paper we provide a comprehensive set of estimators of the most common statistics in population genetics based on the frequency spectrum, namely the Watterson estimator , nucleotide pairwise diversity Π, Tajima's D, Fu and Li's D and F, Fay and Wu's H, McDonald‐Kreitman and HKA tests and , corrected for sequencing errors and ascertainment bias. In a simulation study, we show that pool and individual θ estimates are highly correlated and discuss how the performance of the statistics vary with read depth and sample size in different evolutionary scenarios. As an application, we reanalyse sequences from Drosophila mauritiana and from an evolution experiment in Drosophila melanogaster. These methods are useful for population genetic projects with limited budget, study of communities of individuals that are hard to isolate, or autopolyploid species.     

Synthesis,antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes

A convenient synthetic route and the characterization of complexes trans-[PtCl₂(L)(PPh₃)] (L = Et₂NH (2), (PhCH₂)₂NH (3), (HOCH₂CH₂)₂NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration.     

The glutathione S-transferase gene superfamily: an in silico approach to study the post translational regulation

The use of plants to reclaim contaminated soils and groundwater, known as phytoremediation, is a promising biotechnological strategy which has gained a lot of attention in the last few years. Plants have evolved sophisticated detoxification systems against the toxin chemicals: following the uptake, the compounds are activated so that certain functional groups can conjugate hydrophilic molecules, such as thiols. The resulting conjugates are recognized by the tonoplast transporters and sequestered into the vacuoles. The xenobiotic conjugation with glutathione is mediated by enzymes which belong to the superfamily of glutathione S-transferases (GSTs) catalyzing the nucleophylic attack of the sulphur of glutathione on the electrophilic groups of the cytotoxic substrates therefore playing a crucial role in their degradation. This study was designed to identify the putative correlation between structural and functional characteristics of plant GST classes belonging to different plant species. Consequently, the protein sequences of the expressed GSTs have been retrieved from UniGene, classified and then analyzed in order to assess the evolutionary trend and to predict secondary structure. Moreover, the fingerprint analysis was performed with SCAN Prosite in the attempt to correlate meaningful signature profile and biological information. The results evidenced that all the soluble GSTs have a tendency to assume the α-helix secondary structure followed by random coil and β-sheet. The fingerprint analysis revealed that specific signature profiles related mainly to protein phosphorylation are in the GST classes of all considered species thus suggesting that they might be subjected to reversible activation by phosphorylation-mediated regulation. This approach provides the knowledge of the relationship between presence of conserved signature profile and biological function in the view of future selection of GSTs which might be employed in either mutagenesis or genetic engineering studies.     

Atrioventricular nodal function during atrial fibrillation: Model building and robust estimation

Statistical modeling of atrioventricular (AV) nodal function during atrial fibrillation (AF) is revisited for the purpose of defining model properties and improving parameter estimation. The characterization of AV nodal pathways is made more detailed and the number of pathways is now determined by the Bayesian information criterion, rather than just producing a probability as was previously done. Robust estimation of the shorter refractory period (i.e., of the slow pathway) is accomplished by a Hough-based technique which is applied to a Poincaré plot of RR intervals. The performance is evaluated on simulated data as well as on ECG data acquired from AF patients during rest and head-up tilt test. The simulation results suggest that the refractory period of the slow pathway can be accurately estimated even in the presence of many artifacts. They also show that the number of pathways can be accurately determined. The results from ECG data show that the refined AV node model provides significantly better fit than did the original model, increasing from 85 ± 5% to 88 ± 4% during rest, and from 86 ± 5% to 87 ± 3% during tilt. When assessing the effect of sympathetic stimulation, the AF frequency increased significantly during tilt (6.25 ± 0.58 Hz vs. 6.32 ± 0.61 Hz, p < 0.05, rest vs. tilt) and the prolongation of the refractory periods of both pathways decreased significantly (slow pathway: 0.23 ± 0.20 s vs. 0.11 ± 0.10 s, p < 0.001, rest vs. tilt; fast pathway: 0.24 ± 0.31 s vs. 0.16 ± 0.19 s, p < 0.05, rest vs. tilt). The results show that AV node characteristics can be assessed noninvasively for the purpose of quantifying changes induced by autonomic stimulation.