High rates of conspecific brood parasitism revealed by microsatellite analysis in a diving duck,the common pochard Aythya ferina

Conspecific brood parasitism (CBP) is a reproductive tactic whereby a parasitic female lays its eggs into the nests of other conspecific females. Genetic‐based data on the occurrence of CBP in birds, however, is still relatively scarce. We analysed prevalence of CBP in a ground‐nesting diving duck, the common pochard Aythya ferina, using a set of 17 microsatellites. Compared to related species, our population showed a relatively high level of CBP, with 39% of genotyped pochard eggs laid parasitically and 89% of nests containing ≥ 1 parasitic egg. In addition, we observed relatively high rates of interspecific brood parasitism (13% of eggs), caused predominantly by mallard Anas plathyrhynchos and tufted duck Aythya fuligula. CBP eggs had decreased hatching success compared to host eggs, with 65% of CBP and 95% of non‐CBP genotyped eggs hatching successfully. Our data suggest that this was probably due to improper timing of parasitic egglaying, which compromised synchronised hatching of CBP and host‐eggs. Despite high rates of CBP in our pochard popu lation, fitness costs associated with this reproductive tactic appear to be low for host females since neither clutch size nor host‐egg hatching probability were reduced due to CBP.     

Design,synthesis and structure–activity relationships of zwitterionic spirocyclic compounds as potent CCR1 antagonists

A series of zwitterionic spirocyclic compounds were synthesised. In vitro data revealed that these compounds were potent CCR1 antagonists. In particular, 2, 4, 11 and 20 inhibited CCR1 mediated chemotaxis of THP-1 cells in a functional assay.     

Remodelling of skeletal tissues bone and structural specialisations in an elasmosaurid (Sauropterygia: Plesiosauroidea) from the Upper Cretaceous of Patagonia,Argentina

Elasmosauridae were cosmopolitan Late Cretaceous plesiosaurs with conspicuous morphological diversity. Within this group, vertebral morphology is a criterion for estimating relative age in plesiosaur. On the other hand, the microstructure of plesiosaur bone is considered as indicative of ontogenetic stage. However, knowledge about ontogenetic tissue transformation in different elements of the skeleton is poorly known. Resorption and remodelling of skeletal tissues are required for development and growth, mechanical adaptation, repair and mineral homeostasis of the vertebrate skeleton. This contribution analyses different postcranial elements of a Late Cretaceous elasmosaurid from Patagonia. Characterisation of bone microstructure indicates the presence of compact bone inner organisation in an adult derived plesiosaur from the Cretaceous and that the distribution of bone specialisations depicts conspicuous variations within a single skeleton depending on the skeletal element considered. Bone compactness or degree of remodelling in elasmosaurids is not necessarily correlated with the ontogenetic age of the animal or to costal versus pelagic lifestyles. The available data are still scarce, but we propose a topic of discussion: perhaps the degree of remodelling and compactness also may be related to the activity level and increased mechanical load in different skeletal elements.     

Subcellular localization of proflavine derivative and induction of oxidative stress—In vitro studies

Acridines have been studied for several decades because of their numerous biological effects, especially anticancer activity. Recently, cytotoxicity of novel acridine derivatives, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was confirmed for leukemic cell lines [Bioorg. Med. Chem. 2011, 19, 1790]. The mechanism of action of the most cytotoxic hexyl-AcrDIM was studied in this paper focusing attention on a subcellular distribution of the drug. Accumulation of hexyl-AcrDIM in mitochondria was confirmed after labeling mitochondria with MitoRED using ImageStream Imaging Flow Cytometer. The derivative significantly decreased intracellular ATP level (reduction of ATP level was decreased by vitamin E), and induced oxidative stress (ROS production detected by DHE assay) as well as cell cycle arrest in the S-phase (flow cytometry analysis) already after short-time incubation and induction of apoptosis. Cytotoxicity of hexyl-AcrDIM is closely connected with induction of oxidative stress in cells.     

Synthesis and biological evaluation of 4,5-dihydro-1H-pyrazole derivatives as potential nNOS/iNOS selective inhibitors. Part 2: Influence of diverse substituents in both the phenyl moiety and the acyl group

In a preliminary article, we reported a series of 4,5-dihydro-1H-pyrazole derivatives as neuronal nitric oxide synthase (nNOS) inhibitors. Here we present the data about the inhibition of inducible nitric oxide synthase (iNOS) of these compounds. In general, we can confirm that these pyrazoles are nNOS selective inhibitors. In addition, taking these compounds as a reference, we have designed and synthesized a series of new derivatives by modification of the heterocycle in 1-position, and by introduction of electron-donating or electron-withdrawing substituents in the aromatic ring. These derivatives have been evaluated as nNOS and iNOS inhibitors in order to identify new compounds with improved activity and selectivity. Compound 3r, with three methoxy electron-donating groups in the phenyl moiety, is the most potent nNOS inhibitor, showing good selectivity nNOS/iNOS.     

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.     

Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: Synthesis,crystallography, modeling,kinetic and cellular based studies

Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a series of hydroxamates derived from 1-adamantylacetohydroxamic acid (3a) were prepared. From this group of compounds, an improved potency of about 17-fold was observed for two derivatives. Detailed mechanistic studies on these structures revealed a competitive inhibition model, with a K_i = 27 nM, which makes these compounds some of the most potent small molecule, non-peptidic BoNT/A LC inhibitors reported to date.     

Dynamics of Influenza Virus and Human Host Interactions During Infection and Replication Cycle

The replication and life cycle of the influenza virus is governed by an intricate network of intracellular regulatory events during infection, including interactions with an even more complex system of biochemical interactions of the host cell. Computational modeling and systems biology have been successfully employed to further the understanding of various biological systems, however, computational studies of the complexity of intracellular interactions during influenza infection is lacking. In this work, we present the first large-scale dynamical model of the infection and replication cycle of influenza, as well as some of its interactions with the host’s signaling machinery. Specifically, we focus on and visualize the dynamics of the internalization and endocytosis of the virus, replication and translation of its genomic components, as well as the assembly of progeny virions. Simulations and analyses of the models dynamics qualitatively reproduced numerous biological phenomena discovered in the laboratory. Finally, comparisons of the dynamics of existing and proposed drugs, our results suggest that a drug targeting PB1:PA would be more efficient than existing Amantadin/Rimantaine or Zanamivir/Oseltamivir.     

Population structure and residency of whale sharks Rhincodon typus at Utila,Bay Islands,Honduras

There were 479 reported whale shark Rhincodon typus encounters between 1999 and 2011 at the island of Utila, which forms part of the Meso‐American Barrier Reef System (MBRS) in the western Caribbean Sea. The majority of R. typus were found to feed on small bait fish associated with various tuna species. Ninety‐five individual R. typus, ranging from 2 to 11 m total length (L_T), were identified through their unique spot patterns. A significant male bias (65%) was present. There was no significant difference between the mean ± s.d . L_T of female (6·66 ± 1·65 m) and male (6·25 ± 1·60 m) R. typus. Most R. typus were transient to Utila, with 78% sighted only within a single calendar year, although some individuals were sighted in up to 5 years. Mean residency time was modelled to be 11·76 days using maximum likelihood methods.