Leukocyte kinetics and bacterial clearance during pneumonia and contributions of ICAM-1.

is a leading cause of community-acquired pneumonia. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is highly expressed on the pulmonary capillary endothelium, alveolar epithelium, and other cell types within the lung. ICAM-1 plays important roles in leukocyte adhesion, migration, and motility.

JASPER: Fast, powerful, multitrait association testing in structured samples gives insight on pleiotropy in gene expression.

Joint association analysis of multiple traits with multiple genetic variants can provide insight into genetic architecture and pleiotropy, improve trait prediction, and increase power for detecting association. Furthermore, some traits are naturally high-dimensional, e.g.

The evolution of passive dispersal versus habitat selection have differing emergent consequences in metacommunities.

Dispersal among local communities is fundamental to the metacommunity concept but is only important to the metacommunity structure if dispersal causes distortions of species abundances away from what local ecological conditions favour. We know from much previous work that dispersal can cause such abundance distortions. However, almost all previous theoretical studies have only considered one species alone or two interacting species (e.

The complex circuitry of interactions determining coexistence among plants and mycorrhizal fungi.

We present a mechanistic model of coexistence among a mycorrhizal fungus and one or two plant species that compete for a single nutrient. Plant-fungal coexistence is more likely if the fungus is better at extracting the environmental nutrient than the plant and the fungus acquires carbon from the plant above a minimum rate. When they coexist, their interaction can shift from mutualistic to parasitic at high nutrient availability.

ADELLE: A global testing method for Trans-eQTL mapping.

Understanding the genetic regulatory mechanisms of gene expression is a challenging and ongoing problem. Genetic variants that are associated with expression levels are readily identified when they are proximal to the gene (i.e.

Overcoming the "feast or famine" effect: improved interaction testing in genome-wide association studies.

In genetic association analysis of complex traits, detection of interaction (either GxG or GxE) can help to elucidate the genetic architecture and biological mechanisms underlying the trait. Detection of interaction in a genome-wide interaction study (GWIS) can be methodologically challenging for various reasons, including a high burden of multiple comparisons when testing for epistasis between all possible pairs of a set of genomewide variants, as well as heteroscedasticity effects occurring in the presence of GxG or GxE interaction. In this paper, we address the problem of an even more striking phenomenon that we call the "feast or famine" effect that occurs when testing interaction in a genomewide context.

JASPER: fast, powerful, multitrait association testing in structured samples gives insight on pleiotropy in gene expression.

Joint association analysis of multiple traits with multiple genetic variants can provide insight into genetic architecture and pleiotropy, improve trait prediction and increase power for detecting association. Furthermore, some traits are naturally high-dimensional, e.g.

BRASS: Permutation methods for binary traits in genetic association studies with structured samples.

In genetic association analysis of complex traits, permutation testing can be a valuable tool for assessing significance when the distribution of the test statistic is unknown or not well-approximated. This commonly arises, e.g, in tests of gene-set, pathway or genome-wide significance, or when the statistic is formed by machine learning or data adaptive methods.

Neutrophils sing "IL[-10] be seeing you" in the lungs during pneumonia.

Mechanisms of regulating the beneficial and harmful capabilities of neutrophils include IL-10/IL-10RA signaling in neutrophils that limits clearance of Streptococcus pneumoniae and accumulation of neutrophils in pneumonic lung tissue.

Eco-evolutionary feedbacks among pollinators, herbivores, and their plant resources.

Eco-evolutionary feedbacks among multiple species occur when one species affects another species' evolution via its effects on the abundance and traits of a shared partner species. What happens if those two species enact opposing effects on their shared partner's population growth? Furthermore, what if those two kinds of interactions involve separate traits? For example, many plants produce distinct suites of traits that attract pollinators (mutualists) and deter herbivores (antagonists). Here, we develop a model to explore how pollinators and herbivores may influence each other's interactions with a shared plant species via evolutionary effects on the plant's nectar and toxin traits.

Environmental Conditions during Development Affect Sexual Selection through Trait-Fitness Relationships.

AbstractSexual selection can be shaped by spatial variation in environmental features among populations. Differences in sexual selection among populations generated through the effects of the environment could be shaped via four paths: differences in mean absolute fitness, differences in the means or variances of phenotypes, or differences in the absolute fitness-trait function relationship. Because sexual selection occurs only during the adult life stage, most studies have focused on identifying environmental features that influence these metrics of fitness and trait distributions among adults.

MicroRNAs as Indicators into the Causes and Consequences of Whole-Genome Duplication Events.

Whole-genome duplications (WGDs) have long been considered the causal mechanism underlying dramatic increases to morphological complexity due to the neo-functionalization of paralogs generated during these events. Nonetheless, an alternative hypothesis suggests that behind the retention of most paralogs is not neo-functionalization, but instead the degree of the inter-connectivity of the intended gene product, as well as the mode of the WGD itself. Here, we explore both the causes and consequences of WGD by examining the distribution, expression, and molecular evolution of microRNAs (miRNAs) in both gnathostome vertebrates as well as chelicerate arthropods.

The M2a Macrophage Phenotype Accompanies Pulmonary Granuloma Resolution in Knock-Out Mice Instilled with Multiwall Carbon Nanotubes.

Sarcoidosis is a chronic disease with unknown etiology and pathophysiology, characterized by granuloma formation. Matrix Metalloproteinase-12 (MMP12) is an elastase implicated in active granulomatous sarcoidosis. Previously, we reported that oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) into C57Bl/6 mice induced sarcoid-like granulomas and upregulation of MMP12.

The Evolution of Resource Provisioning in Pollination Mutualisms.

AbstractResource dynamics influence the contemporary ecology of consumer-resource mutualisms. Suites of resource traits, such as floral nectar components, also evolve in response to different selective pressures, changing the ecological dynamics of the interacting species at the evolutionary equilibrium. Here we explore the evolution of resource-provisioning traits in a biotically pollinated plant that produces nectar as a resource for beneficial consumers.

When Ecology Fails: How Reproductive Interactions Promote Species Coexistence.

That species must differ ecologically is often viewed as a fundamental condition for their stable coexistence in biological communities. Yet, recent work has shown that ecologically equivalent species can coexist when reproductive interactions and sexual selection regulate population growth. Here, we review theoretical models and highlight empirical studies supporting a role for reproductive interactions in maintaining species diversity.

Matrix Metalloproteinase-12 Is Required for Granuloma Progression.

Background: Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by granuloma formation. Mechanisms for chronic persistence of granulomas are unknown. Matrix Metalloproteinase-12 (MMP12) degrades extracellular matrix elastin and enables infiltration of immune cells responsible for inflammation and granuloma formation.

Impaired mitochondrial function of alveolar macrophages in carbon nanotube-induced chronic pulmonary granulomatous disease.

Human exposure to carbon nanotubes (CNT) has been associated with the development of pulmonary sarcoid-like granulomatous disease. Our previous studies demonstrated that multi-walled carbon nanotubes (MWCNT) induced chronic pulmonary granulomatous inflammation in mice. Granuloma formation was accompanied by decreased peroxisome proliferator-activated receptor gamma (PPARγ) and disrupted intracellular lipid homeostasis in alveolar macrophages.

Disentangling ecologically equivalent from neutral species: The mechanisms of population regulation matter.

The neutral theory of biodiversity explored the structure of a community of ecologically equivalent species. Such species are expected to display community drift dynamics analogous to neutral alleles undergoing genetic drift. While entire communities of species are not ecologically equivalent, recent field experiments have documented the existence of guilds of such neutral species embedded in real food webs.

Increased levels of superoxide dismutase suppress meiotic segregation errors in aging oocytes.

The risk of meiotic segregation errors increases dramatically during a woman's thirties, a phenomenon known as the maternal age effect. In addition, several lines of evidence indicate that meiotic cohesion deteriorates as oocytes age. One mechanism that may contribute to age-induced loss of cohesion is oxidative damage.

Limiting Similarity? The Ecological Dynamics of Natural Selection among Resources and Consumers Caused by Both Apparent and Resource Competition.

Much of ecological theory presumes that natural selection should foster species coexistence by phenotypically differentiating competitors so that the stability of the community is increased, but whether this will actually occur is a question of the ecological dynamics of natural selection. I develop an evolutionary model of consumer-resource interactions based on MacArthur's and Tilman's classic works, including both resource and apparent competition, to explore what fosters or retards the differentiation of resources and their consumers. Analyses of this model predict that consumers will differentiate only on specific ranges of environmental gradients (e.

Alveolar Macrophage ABCG1 Deficiency Promotes Pulmonary Granulomatous Inflammation.

Pulmonary granuloma formation is a complex and poorly understood response to inhaled pathogens and particulate matter. To explore the mechanisms of pulmonary granuloma formation and maintenance, our laboratory has developed a multiwall carbon nanotube (MWCNT)-induced murine model of chronic granulomatous inflammation. We have demonstrated that the MWCNT model closely mimics pulmonary sarcoidosis pathophysiology, including the deficiency of alveolar macrophage ATP-binding cassette (ABC) lipid transporters ABCA1 and ABCG1.

PPAR-gamma pathways attenuate pulmonary granuloma formation in a carbon nanotube induced murine model of sarcoidosis.

Peroxisome proliferator activated receptor gamma (PPARγ), a ligand activated nuclear transcription factor, is constitutively expressed in alveolar macrophages of healthy individuals. PPARγ deficiencies have been noted in several lung diseases including the alveolar macrophages of pulmonary sarcoidosis patients. We have previously described a murine model of multiwall carbon nanotubes (MWCNT) induced pulmonary granulomatous inflammation which bears striking similarities to pulmonary sarcoidosis, including the deficiency of alveolar macrophage PPARγ.

Female mate preferences on high-dimensional shape variation for male species recognition traits.

Females in many animal species must discriminate between conspecific and heterospecific males when choosing mates. Such mating preferences that discriminate against heterospecifics may inadvertently also affect the mating success of conspecific males, particularly those with more extreme phenotypes. From this expectation, we hypothesized that female mate choice should cause Enallagma females (Odonata: Coenagrionidae) to discriminate against conspecific males with more extreme phenotypes of the claspers males use to grasp females while mating - the main feature of species mate recognition in these species.