Environmental,geographical and time-related impacts on avian malaria infections in native and introduced populations of house sparrows (Passer domesticus), a globally invasive species

Aim

The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations.

Location

Global.

Time period

2002–2019.

Major taxa studied

Avian Plasmodium parasites in house sparrows.

Methods

We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests.

Results

Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected.

Main conclusions

Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows.     

Pentabromopseudilin: a myosin V inhibitor suppresses TGF-β activity by recruiting the type II TGF-β receptor to lysosomal degradation

Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial–mesenchymal transition in epithelial cells. PBrP inhibits TGF-β signalling by reducing the cell-surface expression of type II TGF-β receptor (TβRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TβRII turnover and the subsequent reduction of TGF-β signalling. Because, TGF-β signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.     

Large-scale recording of neurons by movable silicon probes in behaving rodents

A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of neurons and circuits requires methods with the spatial selectivity and temporal resolution appropriate for mechanistic analysis of neural ensembles in the behaving animal, i.e. recording of representatively large samples of isolated single neurons. Ensemble monitoring of neuronal activity has progressed remarkably in the past decade in both small and large-brained animals, including human subjects. Multiple-site recording with silicon-based devices are particularly effective because of their scalability, small volume and geometric design. Here, we describe methods for recording multiple single neurons and local field potential in behaving rodents, using commercially available micro-machined silicon probes with custom-made accessory components. There are two basic options for interfacing silicon probes to preamplifiers: printed circuit boards and flexible cables. Probe supplying companies (http://www.neuronexustech.com/; http://www.sbmicrosystems.com/; http://www.acreo.se/) usually provide the bonding service and deliver probes bonded to printed circuit boards or flexible cables. Here, we describe the implantation of a 4-shank, 32-site probe attached to flexible polyimide cable, and mounted on a movable microdrive. Each step of the probe preparation, microdrive construction and surgery is illustrated so that the end user can easily replicate the process.     

Enzyme activity in the crowded milieu

The cytosol of a cell is a concentrated milieu of a variety of different molecules, including small molecules (salts and metabolites) and macromolecules such as nucleic acids, polysaccharides, proteins and large macromolecular complexes. Macromolecular crowding in the cytosolic environment is proposed to influence various properties of proteins, including substrate binding affinity and enzymatic activity. Here we chose to use the synthetic crowding agent Ficoll, which is commonly used to mimic cytosolic crowding conditions to study the crowding effect on the catalytic properties of glycolytic enzymes, namely phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, and acylphosphatase. We determined the kinetic parameters of these enzymes in the absence and in the presence of the crowding agent. We found that the Michaelis constant, K(m), and the catalytic turnover number, k(cat), of these enzymes are not perturbed by the presence of the crowding agent Ficoll. Our results support earlier findings which suggested that the Michaelis constant of certain enzymes evolved in consonance with the substrate concentration in the cell to allow effective enzyme function in bidirectional pathways. This conclusion is further supported by the analysis of nine other enzymes for which the K(m) values in the presence and absence of crowding agents have been measured.     

Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients

A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163(+) anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy.     

Impedance of the electrogenic Cl− pump inAcetabularia: Electrical frequency entrainements,voltage-sensitivity,and reaction kinetic interpretation

Summary Reaction kinetic analysis of the electrical properties of the electrogenic Cl^– pump inAcetabularia has been extended from steady-state to nonsteady-state conditions: electrical frequency responses of theAcetabularia membrane have been measured over the range from 1 Hz to 10 kHz at transmembrane potential differences across the plasmalemma (V _m ) between –70 and –240 mV using voltage-clamp techniques. The results are well described by an electrical equivalent circuit with three parallel limbs: a conventional membrane capacitancec _m , a steadystate conductanceg _o (predominantly of the pump pathway plus a minor passive ion conductance) and a conductanceg _s in series with a capacitancec _p which are peculiar to the temporal behavior of the pump. The absolute values and voltage sensitivities of these four elements have been determined:c _m of about 8 mF m^–2 turned out to be voltage insensitive; it is considered to be normal.g _o is voltage sensitive and displays a peak of about 80 S m^–2 around –180 mV. Voltage sensitivity ofg _s could not be documented due to large scatter ofg _s (around 80 S m^–2).c _p behaved voltage sensitive with a notch of about 20 mF m^–2 around –180 mV, a peak of about 40 mF m^–2 at –120 mV and vanishing at –70 mV. When these data are compared with the predictions of nonsteady-state electrical properties of charge transport systems (U.-P. Hansen, J. Tittor, D. Gradmann, 1983,J. Membrane Biol. in press), model A (redistribution of states within the reaction cycle) consistently provides magnitude and voltage sensitivity of the elementsg _o ,g _s andc _p of the equivalent circuit, when known kinetic parameters of the pump are used for the calculations. This analysis results in a density of pump elements in theAcetabularia plasmalemma of about 50 nmol m^–2. The dominating rate constants for the redistribution of the individual states of the pump in the electric field turn out to be in the range of 500 sec^–1, under normal conditions.     

High surface hydrophobicity ofStaphylococcus aureus as revealed by hydrophobic interaction chromatography

Hydrophobic interaction chromatography (HIC) on Octyl Sepharose^R in a column procedure was used to compare the relative surface hydrophobicity ofStaphylococcus aureus reference strains, protein A-negative mutants, and strains isolated from bovine mastitis. High protein A-producing strains (Cowan 1 and clinical isolate SA 17970) showed a higher relative surface hydrophobicity than did strains producing a low amount of protein A. One encapsulatedS. aureus strain (Smith diffuse) did not bind to the gel, while an unencapsulated variant showed binding properties similar to weak protein A-producing strains. Studies onS. aureus strains isolated from bovine mastitis revealed a good correlation between adsorption to Octyl Sepharose and the production of protein A. Results indicate that protein A and probably other surface proteins such as fibronectin-binding protein contribute to the high relative surface hydrophobicity ofS. aureus.