Structural basis of the zinc- and terbium-mediated inhibition of ferroxidase activity in Dps ferritin-like proteins

Streptococcus suis Dpr is an iron-binding protein involved in oxidative stress resistance. It belongs to the bacterial Dps protein family whose members form dodecameric assemblies. Previous studies have shown that zinc and terbium inhibit iron incorporation in Listeria innocua Dps protein. In order to gain structural insights into the inhibitory effect of zinc and terbium, the crystal structures of Streptococcus suis Dpr complexes with these ions were determined at 1.8 A and 2.1 A, respectively. Both ions were found to bind at the ferroxidase center and in the same location as iron. In addition, a novel zinc-binding site formed by His40 and His44 was identified. Both His residues were found to be present within all known Streptococcus suis Dpr variants and in Streptococcus pneumoniae, Streptococcus gordonii, and Streptococcus sanguinis Dpr proteins. Amino acid sequence alignment of Dpr with other Dps family members revealed that His44 is highly conserved, in contrast to His40. The inhibitory effect of zinc and terbium on iron oxidation in Dpr was studied in vitro, and it was found that both ions at concentrations >0.2 mM almost completely abolish iron binding. These results provide a structural basis for the inhibitory effect of zinc and terbium in the Dps family of proteins, and suggest a potential role of the Dps proteins in zinc detoxification mechanisms involving the second zinc-binding site.     

Comparison between the allergenic airborne pollen in Trieste and at Lozzo di Cadore (Italy) in 1989

Summary A comparative study was carried out between aeroallergenic pollen spectra in Trieste and at Lozzo di Cadore. The two localities were found to be different on a five-day running mean basis as to the 8 pollen taxa monitored by the National Aerobiological Monitoring Network managed by the Italian Association of Aerobiology (AIA). In the zone of Lozzo the pollination curve of the spring flowering taxa showed a lag of about one month due to the colder climate. Lozzo di Cadore showed a poor airborne pollen content,Corylus and Graminaceae being prevailing. Trieste has a higher airborne pollen diversity and longer pollination times because of its higher floristic and vegetational complexity. In Trieste the allergenic pollen spectrum showed great quantities ofOstrya, Quercus, Oleaceae, Graminaceae and of ruderal taxa, widespread over the area, due to man's influence.     

Functional selective oxytocin-derived agonists discriminate between individual G protein family subtypes

We used a bioluminescence resonance energy transfer biosensor to screen for functional selective ligands of the human oxytocin (OT) receptor. We demonstrated that OT promoted the direct engagement and activation of G(q) and all the G(i/o) subtypes at the OT receptor. Other peptidic analogues, chosen because of specific substitutions in key OT structural/functional residues, all showed biased activation of G protein subtypes. No ligand, except OT, activated G(oA) or G(oB), and, with only one exception, all of the peptides that activated G(q) also activated G(i2) and G(i3) but not G(i1), G(oA), or G(oB), indicating a strong bias toward these subunits. Two peptides (DNalOVT and atosiban) activated only G(i1) or G(i3), failed to recruit β-arrestins, and did not induce receptor internalization, providing the first clear examples of ligands differentiating individual G(i/o) family members. Both analogs inhibited cell proliferation, showing that a single G(i) subtype-mediated pathway is sufficient to prompt this physiological response. These analogs represent unique tools for examining the contribution of G(i/o) members in complex biological responses and open the way to the development of drugs with peculiar selectivity profiles. This is of particular relevance because OT has been shown to improve symptoms in neurodevelopmental and psychiatric disorders characterized by abnormal social behaviors, such as autism. Functional selective ligands, activating a specific G protein signaling pathway, may possess a higher efficacy and specificity on OT-based therapeutics.     

Specific interactions between Epac1, β-arrestin2 and PDE4D5 regulate β-adrenergic receptor subtype differential effects on cardiac hypertrophic signaling

β1 and β2 adrenergic receptors (βARs) are highly homologous but fulfill distinct physiological and pathophysiological roles. Here we show that both βAR subtypes activate the cAMP-binding protein Epac1, but they differentially affect its signaling. The distinct effects of βARs on Epac1 downstream effectors, the small G proteins Rap1 and H-Ras, involve different modes of interaction of Epac1 with the scaffolding protein β-arrestin2 and the cAMP-specific phosphodiesterase (PDE) variant PDE4D5. We found that β-arrestin2 acts as a scaffold for Epac1 and is necessary for Epac1 coupling to H-Ras. Accordingly, knockdown of β-arrestin2 prevented Epac1-induced histone deacetylase 4 (HDAC4) nuclear export and cardiac myocyte hypertrophy upon β1AR activation. Moreover, Epac1 competed with PDE4D5 for interaction with β-arrestin2 following β2AR activation. Dissociation of the PDE4D5–β-arrestin2 complex allowed the recruitment of Epac1 to β2AR and induced a switch from β2AR non-hypertrophic signaling to a β1AR-like pro-hypertrophic signaling cascade. These findings have implications for understanding the molecular basis of cardiac myocyte remodeling and other cellular processes in which βAR subtypes exert opposing effects.     

<Emphasis Type="Italic">Taenia arctos</Emphasis> n. sp. (Cestoda: Cyclophyllidea: Taeniidae) from its definitive (brown bear <Emphasis Type="Italic">Ursus arctos</Emphasis> Linnaeus) and intermediate (moose/elk <Emphasis Type="Italic">Alces</Emphasis> spp.) hosts

Taenia arctos n. sp. (Cestoda: Cyclophyllidea: Taeniidae) is described from the brown bear Ursus arctos Linnaeus (definitive host) and moose/elk Alces spp. (intermediate hosts) from Finland (type-locality) and Alaska, USA. The independent status of the new species and the conspecificity of its adults and metacestodes have been recently confirmed by the mtDNA sequence data of Lavikainen et al. (2011; Parasitology International, 60, 289–295). Special reference is given to morphological differences between the new species and T. krabbei Moniez, 1879 (definitive hosts primarily canines for the latter), both of which use the moose/elk (Alces spp.) as intermediate hosts (the latter also uses Rangifer and perhaps other northern ruminants), and between the new species and T. ursina Linstow, 1893, both of which use the brown bear U. arctos as a definitive host. New morphological data are also provided for adults and cysticerci of T. krabbei. The analysis includes potentially useful morphometric features that have not been previously applied to Taenia spp.     

Magnetic properties and structural characterization of iron oxide nanoparticles formed by <Emphasis Type="Italic">Streptococcus suis</Emphasis> Dpr and four mutants

Streptococcus suis Dpr belongs to the Dps family of bacterial and archaeal proteins that oxidize Fe²⁺ to Fe³⁺ to protect microorganisms from oxidative damage. The oxidized iron is subsequently deposited as ferrihydrite inside a protein cavity, resulting in the formation of an iron core. The size and the magnetic properties of the iron core have attracted considerable attention for nanotechnological applications in recent years. Here, the magnetic and structural properties of the iron core in wild-type Dpr and four cavity mutants were studied. All samples clearly demonstrated a superparamagnetic behavior in superconducting quantum interference device magnetometry and Mössbauer spectroscopy compatible with that of superparamagnetic ferrihydrite nanoparticles. However, all the mutants exhibited higher magnetic moments than the wild-type protein. Furthermore, measurement of the iron content with inductively coupled plasma mass spectrometry revealed a smaller amount of iron in the iron cores of the mutants, suggesting that the mutations affect nucleation and iron deposition inside the cavity. The X-ray crystal structures of the mutants revealed no changes compared with the wild-type crystal structure; thus, the differences in the magnetic moments could not be attributed to structural changes in the protein. Extended X-ray absorption fine structure measurements showed that the coordination geometry of the iron cores of the mutants was similar to that of the wild-type protein. Taken together, these results suggest that mutation of the residues that surround the iron storage cavity could be exploited to selectively modify the magnetic properties of the iron core without affecting the structure of the protein and the geometry of the iron core.     

Aerobiology of Urticaceae pollen in Trieste (NE Italy)

The aerobiological behaviour of Urticaceae in Trieste and the correlations with the meteorological parameters were examined. Airborne pollen was collected from 1990 to 1999 using a Hirst type spore trap (Burkard) and the data interpretation was performed according to the standard method adopted by the Italian Aeroallergen Network. The main pollen season of Urticaceae in Trieste goes from mid-April to mid-September. The highest values occur in May and June. Although different seasonal patterns are found every year, the main peak occurs on average at the beginning of May, followed by other decreasing peaks until September. Thecumulative counts vary greatly over the years, with a mean value of 18.315 p/m³. The maximum annual total pollen grains was registered in 1996 and the minimum in 1991. Spearman's correlation was used to establish the relationship between the daily pollen counts and the daily meteorological data both considering their original quantitative values and transformed values according to their day by day changes. Daily pollen concentrations present usually positive correlation with temperature, negative with rainfall and wind speed and no correlation with humidity. Better results were obtained with transformed values.     

Climate Change Promotes the Emergence of Serious Disease Outbreaks of Filarioid Nematodes

Filarioid parasites represent major health hazards with important medical, veterinary, and economic implications, and considerable potential to affect the everyday lives of tens of millions of people globally (World Health Organization, 2007). Scenarios for climate change vary latitudinally and regionally and involve direct and indirect linkages for increasing temperature and the dissemination, amplification, and invasiveness of vector-borne parasites. High latitude regions are especially influenced by global climate change and thus may be prone to altered associations and dynamics for complex host-pathogen assemblages and emergence of disease with cascading effects on ecosystem structure. Although the potential for substantial ecological perturbation has been identified, few empirical observations have emanated from systems across the Holarctic. Coincidental with decades of warming, and anomalies of high temperature and humidity in the sub-Arctic region of Fennoscandia, the mosquito-borne filarioid nematode Setaria tundra is now associated with emerging epidemic disease resulting in substantial morbidity and mortality for reindeer and moose. We describe a host-parasite system that involves reindeer, arthropods, and nematodes, which may contribute as a factor to ongoing declines documented for this ungulate species across northern ecosystems. We demonstrate that mean summer temperatures exceeding 14°C drive the emergence of disease due to S. tundra. An association between climate and emergence of filarioid parasites is a challenge to ecosystem services with direct effects on public health, sustainability of free-ranging and domestic ungulates, and ultimately food security for subsistence cultures at high latitudes.     

Predicting range expansion of an ectoparasite – the effect of spring and summer temperatures on deer ked Lipoptena cervi (Diptera: Hippoboscidae) performance along a latitudinal gradient

The range expansion of organisms towards higher latitudes and altitudes is often limited by colder temperatures and the shorter growth season. In parasites, survival outside the host is most likely to affect their potential establishment in novel environments. We conducted a large scale transplant experiment to predict the potential spread of the deer ked Lipoptena cervi (Diptera: Hippoboscidae), a blood‐feeding ectoparasite of boreal cervids. We studied the off‐host survival and pupal development of deer ked in five sites along a latitudinal gradient reaching from its current range in central Finland to northernmost Fennoscandia. We showed that the deer ked is able to survive and complete its development even in arctic environments, 500 km northwards beyond the current range. Performance deteriorated steadily towards north, where lower summer temperatures prolonged the developmental period and shortened the suitable host search time by several weeks. The relevance of the experiments for estimating the spread of deer ked to the north is discussed.