Dusp5 negatively regulates IL‐33‐mediated eosinophil survival and function

Mitogen-activated protein kinase (MAPK) activation controls diverse cellular functions including cellular survival, proliferation, and apoptosis. Tuning of MAPK activation is counter-regulated by a family of dual-specificity phosphatases (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL-33Rα (ST2L)/IL-1α accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-κB pathways. We demonstrate here that DUSP5 is expressed in eosinophils, is upregulated following IL-33 stimulation and regulates IL-33 signaling. Dusp5^−/− mice have prolonged eosinophil survival and enhanced eosinophil effector functions following infection with the helminth Nippostrongylus brasiliensis. IL-33-activated Dusp5^−/− eosinophils exhibit increased cellular ERK1/2 activation and BCL-X_L expression that results in enhanced eosinophil survival. In addition, Dusp5^−/− eosinophils demonstrate enhanced IL-33-mediated activation and effector functions. Together, these data support a role for DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival.     

Impacts of nest predators and weather on reproductive success and population limitation in a long‐distance migratory songbird

Although avian nesting success is much studied, little is known about the relative importance of the factors that contribute to annual reproductive success and population limitation, especially for long‐distance migratory songbird species. We combined a field experiment limiting access to nests by mammalian predators with modeling of long‐term field data of American redstarts (Parulidae: Setophaga ruticilla) to assess the effects of multiple environmental variables on breeding success and population limitation. Experimental treatment (baffles placed around tree boles beneath active nests; n = 71) increased nesting success of this single‐brooded species significantly (77 vs 50% in controls; n = 343), demonstrating that scansorial mammals, primarily red squirrels Tamiasciurus hudsonicus and eastern chipmunks Tamias striatus, reduced reproductive success. Based on unbaffled nests (n = 466), daily nest survival varied annually, and was positively influenced by May temperature and negatively by sciurid nest predator abundance. Daily nest survival was also influenced positively by June rainfall, and declined with nest age but not with calendar date. Since nest failure was overwhelmingly caused by nest predation, these significant climate and nest‐age effects in our models are indirect, likely influencing nest predator and/or nesting bird behaviors that in turn influenced nest predation. Redstart population density had no effect on nesting success, after accounting for other factors. Annual reproductive success accounted for 34% of the variability in annual population change in redstarts in our study area. Our findings document 1) breeding season population limitation in this species, 2) a link between tree masting and bird population dynamics via mammal population fluctuations, 3) the independent contributions of summer versus winter population processes in a migratory species, and 4) the potential complexity of climate‐biotic interactions.     

The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations

Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), is estimated to infect a new host every second. While analyses of genetic data from natural populations of M.tb have emphasized the role of genetic drift in shaping patterns of diversity, the influence of natural selection on this successful pathogen is less well understood. We investigated the effects of natural selection on patterns of diversity in 63 globally extant genomes of M.tb and related pathogenic mycobacteria. We found evidence of strong purifying selection, with an estimated genome-wide selection coefficient equal to −9.5×10⁻⁴ (95% CI −1.1×10⁻³ to −6.8×10⁻⁴); this is several orders of magnitude higher than recent estimates for eukaryotic and prokaryotic organisms. We also identified different patterns of variation across categories of gene function. Genes involved in transport and metabolism of inorganic ions exhibited very low levels of non-synonymous polymorphism, equivalent to categories under strong purifying selection (essential and translation-associated genes). The highest levels of non-synonymous variation were seen in a group of transporter genes, likely due to either diversifying selection or local selective sweeps. In addition to selection, we identified other important influences on M.tb genetic diversity, such as a 25-fold expansion of global M.tb populations coincident with explosive growth in human populations (estimated timing 1684 C.E., 95% CI 1620–1713 C.E.). These results emphasize the parallel demographic histories of this obligate pathogen and its human host, and suggest that the dominant effect of selection on M.tb is removal of novel variants, with exceptions in an interesting group of genes involved in transportation and defense. We speculate that the hostile environment within a host imposes strict demands on M.tb physiology, and thus a substantial fitness cost for most new mutations. In this respect, obligate bacterial pathogens may differ from other host-associated microbes such as symbionts.     

New World Bats Harbor Diverse Influenza A Viruses

Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.     

Effects of Prescribed Fires on Young Valley Oak Trees at a Research Restoration Site in the Central Valley of California

Woodland restoration sites planted with Quercus lobata (valley oak) often have serious invasions of nonnative annual grasses and thistles. Although prescribed fire can effectively control these exotics, restoration managers may be reluctant to use fire if it causes substantial mortality of recently planted saplings. We studied the effects of prescribed fires on the survival and subsequent growth of 5‐ and 6‐year‐old valley oak saplings at a research field near Davis, California. One set of blocks was burned in summer 2003 at a time that would control yellow star thistle, a second set of blocks was burned in spring 2004 at a time that would control annual grasses, and a third set was left unburned. Very few oaks died as a result of either fire (3–4%). Although a large proportion was top‐killed (66–72%), virtually all these were coppiced and most saplings over 300 cm tall escaped top‐kill. Tree height, fire temperature, and understory biomass were all predictive of the severity of sapling response to fire. Although the mean sapling height was initially reduced by the fires, the growth rates of burned saplings significantly exceeded the growth rates of unburned control trees for 2 years following the fires. By 2–3 years after the fires, the mean height of spring‐ and summer‐burned saplings was similar to that of the unburned control saplings. The presence of valley oak saplings does not appear to preclude the use of a single prescribed burn to control understory invasives, particularly if saplings are over 300 cm tall.     

Spatial dynamics of human-origin H1 influenza A virus in North American swine

The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human health, relatively little is known about the phylogeography of swine influenza viruses in the United States. This study utilizes an expansive data set of hemagglutinin (HA1) sequences (n = 1516) from swine influenza viruses collected in North America during the period 2003-2010. With these data we investigate the spatial dissemination of a novel influenza virus of the H1 subtype that was introduced into the North American swine population via two separate human-to-swine transmission events around 2003. Bayesian phylogeographic analysis reveals that the spatial dissemination of this influenza virus in the US swine population follows long-distance swine movements from the Southern US to the Midwest, a corn-rich commercial center that imports millions of swine annually. Hence, multiple genetically diverse influenza viruses are introduced and co-circulate in the Midwest, providing the opportunity for genomic reassortment. Overall, the Midwest serves primarily as an ecological sink for swine influenza in the US, with sources of virus genetic diversity instead located in the Southeast (mainly North Carolina) and South-central (mainly Oklahoma) regions. Understanding the importance of long-distance pig transportation in the evolution and spatial dissemination of the influenza virus in swine may inform future strategies for the surveillance and control of influenza, and perhaps other swine pathogens.     

Global metabolic phenotyping in an experimental laparotomy model of surgical trauma

Surgical trauma initiates a complex series of metabolic host responses designed to maintain homeostasis and ensure survival. (1)H NMR spectroscopy was applied to intraoperative urine and plasma samples as part of a strategy to analyze the metabolic response of Wistar rats to a laparotomy model. Spectral data were analyzed by multivariate statistical analysis. Principal component analysis (PCA) confirmed that surgical injury is responsible for the majority of the metabolic variability demonstrated between animals (R2 Urine = 81.2% R2 plasma = 80%). Further statistical analysis by orthogonal projection to latent structure discriminant analysis (OPLS-DA) allowed the identification of novel urinary metabolic markers of surgical trauma. Urinary levels of taurine, glucose, urea, creatine, allantoin, and trimethylamine-N-oxide (TMAO) were significantly increased after surgery whereas citrate and 2-oxoglutarate (2-OG) negatively correlated with the intraoperative state as did plasma levels of betaine and tyrosine. Plasma levels of lipoproteins such as VLDL and LDL also rose with the duration of surgery. Moreover, the microbial cometabolites 3-hydroxyphenylpropionate, phenylacetylglycine, and hippurate correlated with the surgical insult, indicating that the gut microbiota are highly sensitive to the global homeostatic state of the host. Metabonomic profiling provides a global overview of surgical trauma that has the potential to provide novel biomarkers for personalized surgical optimization and outcome prediction.