Spontaneous and electric field–controlled front–rear polarization of human keratinocytes

It has long been known that electrical fields (EFs) are able to influence the direction of migrating cells, a process commonly referred to as electrotaxis or galvanotaxis. Most studies have focused on migrating cells equipped with an existing polarity before EF application, making it difficult to delineate EF-specific pathways. Here we study the initial events in front–rear organization of spreading keratinocytes to dissect the molecular requirements for random and EF-controlled polarization. We find that Arp2/3-dependent protrusive forces and Rac1/Cdc42 activity were generally required for both forms of polarization but were dispensable for controlling the direction of EF-controlled polarization. By contrast, we found a crucial role for extracellular pH as well as G protein coupled–receptor (GPCR) or purinergic signaling in the control of directionality. The normal direction of polarization toward the cathode was reverted by lowering extracellular pH. Polarization toward the anode was also seen at neutral pH when GPCR or purinergic signaling was inhibited. However, the stepwise increase of extracellular pH in this scenario led to restoration of cathodal polarization. Overall our work puts forward a model in which the EF uses distinct polarization pathways. The cathodal pathway involves GPCR/purinergic signaling and is dominant over the anodal pathway at neutral pH.     

Pathways activated during human asthma exacerbation as revealed by gene expression patterns in blood

Background

Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations.

Methodology/Principal Findings

Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations.

Conclusions/Significance

This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.     

Prevalence of malaria and related haemosporidian parasites in two shorebird species with different winter habitat distribution

Parasites can have strong effects on host life-history and behaviour, and result in changes in host population dynamics and community structure. We applied a PCR-based technique and examined prevalence of malaria and related haemosporidian parasites in two arctic breeding shorebird species: the Semipalmated Sandpiper (Calidris pusilla) and the Pectoral Sandpiper (C. melanotos). During the non-breeding season, Semipalmated Sandpipers inhabit coastal marine habitats, whereas Pectoral Sandpipers are found in inland areas. In accordance with the hypothesis that the risk of parasite infection is higher in a species wintering in freshwater areas, we found Plasmodium sp. infection during the breeding season only in Pectoral Sandpipers, whereas Semipalmated Sandpipers were parasite free. However, even in Pectoral Sandpipers sampled in the arctic, prevalence of malaria parasites was very low (<3% of individuals, n = 114). Overall, three different Plasmodium sp. lineages were found, one of which has never been described before.     

The ecology of emerging infectious diseases in migratory birds: an assessment of the role of climate change and priorities for future research

Pathogens that are maintained by wild birds occasionally jump to human hosts, causing considerable loss of life and disruption to global commerce. Preliminary evidence suggests that climate change and human movements and commerce may have played a role in recent range expansions of avian pathogens. Since the magnitude of climate change in the coming decades is predicted to exceed climatic changes in the recent past, there is an urgent need to determine the extent to which climate change may drive the spread of disease by avian migrants. In this review, we recommend actions intended to mitigate the impact of emergent pathogens of migratory birds on biodiversity and public health. Increased surveillance that builds upon existing bird banding networks is required to conclusively establish a link between climate and avian pathogens and to prevent pathogens with migratory bird reservoirs from spilling over to humans.     

MalAvi: a public database of malaria parasites and related haemosporidians in avian hosts based on mitochondrial cytochrome b lineages

Research in avian blood parasites has seen a remarkable increase since the introduction of polymerase chain reaction-based methods for parasite identification. New data are revealing complex multihost-multiparasite systems which are difficult to understand without good knowledge of the host range and geographical distribution of the parasite lineages. However, such information is currently difficult to obtain from the literature, or from general repositories such as GenBank, mainly because (i) different research groups use different parasite lineage names, (ii) GenBank entries frequently refer only to the first host and locality at which each parasite was sampled, and (iii) different researchers use different gene fragments to identify parasite lineages. We propose a unified database of avian blood parasites of the genera Plasmodium, Haemoproteus and Leucocytozoon identified by a partial region of their cytochrome b sequences. The database uses a standardized nomenclature to remove synonymy, and concentrates all available information about each parasite in a public reference site, thereby facilitating access to all researchers. Initial data include a list of host species and localities, as well as genetic markers that can be used for phylogenetical analyses. The database is free to download and will be regularly updated by the authors. Prior to publication of new lineages, we encourage researchers to assign names to match the existing database. We anticipate that the value of the database as a source for determining host range and geographical distribution of the parasites will grow with its size and substantially enhance the understanding of this remarkably diverse group of parasites.     

Historical diversification of migration patterns in a passerine bird

Migratory strategies of birds require complex orientation mechanisms, morphological adaptations, and life-history adjustments. From an evolutionary perspective, it is important to know how fast this complex combination of traits can evolve. We analyzed mitochondrial control-region DNA sequences in 241 blackcaps (Sylvia atricapilla) from 12 populations with different migratory behaviors. The sample included sedentary populations in Europe and Atlantic archipelagos and migratory populations with different distances of migration, from regional to intercontinental migrations, and different heading directions (due to a migratory divide in central Europe). There was no genetic structure between migratory and sedentary populations, or among populations from different biogeographic areas (Atlantic islands, the Iberian Peninsula, or the continent), however we found evidence of a genetic structure when comparing populations located on either side of the migratory divide. These findings support an independent evolution of highly divergent migratory strategies in blackcaps, occurring after a postglacial colonization of the continent along western and eastern routes. Accordingly, mismatch-distribution analyses suggested an expansion of blackcaps from a very small population size, and time estimates dated such an expansion during the last postglacial period. However, the populations in Gibraltar, located in a putative Mediterranean refuge, appeared to be independent of these processes, showing evidence of restricted gene flow with other populations and demonstrating insignificant historical changes in effective population size. Our results show that the interruption of gene flow between migratory and sedentary populations is not necessary for the maintenance of such a polymorphism, and that even the most divergent migratory strategies of a bird species are susceptible to evolution in response to historical environmental changes.     

Nestling growth and song repertoire size in great reed warblers: evidence for song learning as an indicator mechanism in mate choice

Females of many songbird species show a preference for mating with males that have larger song repertoires, but the advantages associated with this preference are uncertain. We tested the hypothesis that song complexity can serve as an indicator of male quality because the development of the brain regions underlying song learning and production occurs when young birds typically face nutritional and other stresses, so that song reflects how well a male fared during post-hatch development. A key prediction of this hypothesis is that variation in nestling condition should correspond to variation in the adult song repertoires of individuals. We used data from a long-term study of the great reed warbler (Acrocephalus arundinaceus) to test this prediction, correlating two measures of nestling development with subsequent repertoire size of males. We found that the length of the innermost primary feather, a standard measure of development, significantly predicted first-year repertoire size. The relationship between repertoire size and body mass was nearly significant, in spite of the large variance inherent in this measure. These data support the idea that song may provide females with information about a male's response to developmental stress, which in turn is expected to correlate with indirect or direct benefits she might receive.     

Population differentiation in the redshank (<Emphasis Type="Italic">Tringa totanus</Emphasis>) as revealed by mitochondrial DNA and amplified fragment length polymorphism markers

The redshank (Tringa totanus) is declining throughout Europe and to implement efficient conservation measures, it is important to obtain information about the population genetic structure. The aim of the present study was two-fold. First, we analysed the genetic variation within and between populations in the Baltic region in southern Scandinavia. Evidence of genetic structure would suggest that different populations might require separate management strategies. Second, in an attempt to study large-scale genetic structure we compared the Baltic populations with redshanks from northern Scandinavia and Iceland. This analysis could reveal insights into phylogeography and long-term population history. DNA samples were collected from six breeding sites in Scandinavia presumed to include two subspecies (totanus and britannica) and a further sample from Iceland (subspecies robusta). Two methods were used to study the population genetic structure. Domain II and III of the mitochondrial control region was analysed by DNA sequencing and nuclear DNA was analysed by screening amplified fragment length polymorphism (AFLP) markers. Mitochondrial DNA showed no variation between individuals in domain II. When analysing an 481 bp fragment of domain III seven haplotypes were found among birds. On the basis of mtDNA sequences, redshanks showed some evidence of a recent expansion from a bottlenecked refugial population. Bayesian analyses of AFLP data revealed a significant genetic differentiation between suggested subspecies but not between populations within the Baltic region. Our results indicate that populations of redshanks in Europe constitute at least three separate management units corresponding to the recognised subspecies.     

Temporal and spatial variation of hematozoans in Scandinavian willow warblers

We examined temporal and geographical distribution of Haemoproteus sp. and Plasmodium sp. parasites in Swedish willow warblers, Phylloscopus trochilus. Parasite lineages were detected with molecular methods in 556 birds from 41 sites distributed at distances up to 1,500 km. Two mitochondrial lineages of Haemoproteus sp. were detected, WW1 in 56 birds and WW2 in 75 birds, that differed by 5.2% sequence divergence. We discuss the reasons behind the observed pattern of variation and identify 3 possible causes: (1) variation in the geographic distribution of the vector species, (2) the degree of parasite sharing with other bird species coexisting with the willow warbler, and (3) timing of transmission. Our results support a fundamental and rarely tested assumption of the now classical Hamilton-Zuk hypothesis of sexual selection, namely, that these parasites vary in both time and space. Such fluctuations of parasites and the selection pressure they supposedly impose on the host population are likely to maintain variation in immune system genes in the host population.