Coevolutionary immune system dynamics driving pathogen speciation

We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.Comment: main article: 16 pages, 5 figures; supporting information: 3 page

Resistance to Gray Leaf Spot of Maize: Genetic Architecture and Mechanisms Elucidated through Nested Association Mapping and Near-Isogenic Line Analysis

Citation: Benson, J. M., Poland, J. A., Benson, B. M., Stromberg, E. L., & Nelson, R. J. (2015). Resistance to Gray Leaf Spot of Maize: Genetic Architecture and Mechanisms Elucidated through Nested Association Mapping and Near-Isogenic Line Analysis. Plos Genetics, 11(3), 23. https://doi.org/10.1371/journal.pgen.1005045Gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is one of the most important diseases of maize worldwide. The pathogen has a necrotrophic lifestyle and no major genes are known for GLS. Quantitative resistance, although poorly understood, is important for GLS management. We used genetic mapping to refine understanding of the genetic architecture of GLS resistance and to develop hypotheses regarding the mechanisms underlying quantitative disease resistance (QDR) loci. Nested association mapping (NAM) was used to identify 16 quantitative trait loci (QTL) for QDR to GLS, including seven novel QTL, each of which demonstrated allelic series with significant effects above and below the magnitude of the B73 reference allele. Alleles at three QTL, qGLS1.04, qGLS2.09, and qGLS4.05, conferred disease reductions of greater than 10%. Interactions between loci were detected for three pairs of loci, including an interaction between iqGLS4.05 and qGLS7.03. Near-isogenic lines (NILs) were developed to confirm and fine-map three of the 16 QTL, and to develop hypotheses regarding mechanisms of resistance. qGLS1.04 was fine-mapped from an interval of 27.0 Mb to two intervals of 6.5 Mb and 5.2 Mb, consistent with the hypothesis that multiple genes underlie highly significant QTL identified by NAM. qGLS2.09, which was also associated with maturity (days to anthesis) and with resistance to southern leaf blight, was narrowed to a 4-Mb interval. The distance between major leaf veins was strongly associated with resistance to GLS at qGLS4.05. NILs for qGLS1.04 were treated with the C. zeae-maydis toxin cercosporin to test the role of host-specific toxin in QDR. Cercosporin exposure increased expression of a putative flavin-monooxygenase (FMO) gene, a candidate detoxification-related gene underlying qGLS1.04. This integrated approach to confirming QTL and characterizing the potential underlying mechanisms advances the understanding of QDR and will facilitate the development of resistant varieties

Molecular Events in the Cell Types of the Olfactory Epithelium during Adult Neurogenesis

BACKGROUND: Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium. RESULTS: Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs. CONCLUSIONS: Many of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns were consistent with the transition into a neuronal morphology (neuritogenesis) and later patterns with neuronal homeostasis. Overall, gene expression patterns during adult olfactory neurogenesis showed substantial similarity to those of embryonic brain

Site Conditions Determine a Key Native Plant’s Contribution to Invasion Resistance in Grasslands

Many plant invasion studies in grasslands suggest that resident plants that share functional traits with invaders can reduce invasion by competing for limiting resources. However, since invasion studies often occur in highly controlled plots or microcosms, it is unclear how heterogeneous site conditions alter competitive interactions under realistic scenarios. To explore how landscape heterogeneity affects biotic resistance provided by competitive resident plants, we conducted a field‐based experiment across four sites in California grasslands. Plots contained naturally occurring populations of native Hemizonia congesta, but differed in other characteristics, including litter cover, annual grass cover, soil moisture, and species richness. We invaded plots with the functionally similar nonnative Centaurea solstitalis (yellow starthistle) and, at one site, supplemented one‐half of the established plots with water to test the effects of increasing a limiting resource. As in simplified plots and microcosms, increasing H. congesta abundance reduced starthistle biomass by competing for limited soil moisture, but only in plots with high starthistle germination. We conclude that higher abundances of native H. congesta can reduce starthistle invasion in heterogeneous grasslands, but competition is also affected by both abiotic (soil moisture) and biotic (starthistle germination number) conditions that vary across sites

The persistence of a chlorophyll spectral biosignature from Martian evaporite and spring analogues under Mars-like conditions

Spring and evaporite deposits are considered two of the most promising environments for past habitability on Mars and preservation of biosignatures. Manitoba, Canada hosts the East German Creek (EGC) hypersaline spring complex, and the post impact evaporite gypsum beds of the Lake St. Martin (LSM) impact. The EGC complex has microbial mats, sediments, algae and biofabrics, while endolithic communities are ubiquitous in the LSM gypsum beds. These communities are spectrally detectable based largely on the presence of a chlorophyll absorption band at 670 nm; however, the robustness of this feature under Martian surface conditions was unclear. Biological and biology-bearing samples from EGC and LSM were exposed to conditions similar to the surface of present day Mars (high UV flux, 100 mbar, anoxic, CO_2 rich) for up to 44 days, and preservation of the 670 nm chlorophyll feature and chlorophyll red-edge was observed. A decrease in band depth of the 670 nm band ranging from ∼16 to 80% resulted, with correlations seen in the degree of preservation and the spatial proximity of samples to the spring mound and mineral shielding effects. The spectra were deconvolved to Mars Exploration Rover (MER) Pancam and Mars Science Laboratory (MSL) Mastcam science filter bandpasses to investigate the detectability of the 670 nm feature and to compare with common mineral features. The red-edge and 670 nm feature associated with chlorophyll can be distinguished from the spectra of minerals with features below ∼1000 nm, such as hematite and jarosite. However, distinguishing goethite from samples with the chlorophyll feature is more problematic, and quantitative interpretation using band depth data makes little distinction between iron oxyhydroxides and the 670 nm chlorophyll feature. The chlorophyll spectral feature is observable in both Pancam and Mastcam, and we propose that of the proposed EXOMARS Pancam filters, the PHYLL filter is best suited for its detection

Predictors of Arterial Stiffness in Law Enforcement Officers

Background: Compare arterial stiffness among law enforcement officers (LEOs) versus general population normative values and identify predictors of arterial stiffness in LEOs. Methods: Seventy male LEOs (age: 24–54 years) completed body composition, blood pressures, physical activity level, and carotid-femoral pulse wave velocity (cfPWV) measurements. T-tests and regression analyses were utilized to compare LEO data to normative data and predict cfPWV, respectively. Results: Compared to similar age strata within the general population, cfPWV was lower among LEO’s under 30-years (mean difference = −0.6 m·s−1), but higher among LEOs 50–55-years (mean difference = 1.1 m·s−1). Utilizing regression, age, relative body fat, and diastolic blood pressure explained the greatest variance in LEO’s cfPWV (adj. R2 = 0.56, p \u3c 0.001). Conclusion: This investigation demonstrated that arterial stiffness may progress more rapidly in LEOs and LEOs’ relative body fat and blood pressure may primarily affect arterial stiffness and risk of CVD

The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen \u3cem\u3ePneumocystis murina\u3c/em\u3e Hinders the Ability of Dendritic Cells to Stimulate CD4\u3csup\u3e+\u3c/sup\u3e T Cell Responses

The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors. Trophic forms also suppressed the expression of genes related to antigen processing and presentation, including the gene encoding the major histocompatibility complex (MHC) class II transactivator, CIITA. Stimulation of dendritic cells with trophic forms, but not a mixture of trophic forms and cysts, reduced the expression of MHC class II and the costimulatory molecule CD40 on the surface of the cells. These defects in the expression of MHC class II and costimulatory molecules corresponded with a reduced capacity for trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and polarization. These data are consistent with the delayed innate and adaptive responses previously observed in immunocompetent mice inoculated with trophic forms compared to responses in mice inoculated with a mixture of trophic forms and cysts. We propose that trophic forms broadly inhibit the ability of dendritic cells to fulfill their role as antigen-presenting cells

Critical values for Lawshe's content validity ratio: revisiting the original methods of calculation

YesThe content validity ratio originally proposed by Lawshe is widely used to quantify content validity and yet methods used to calculate the original critical values were never reported. Methods for original calculation of critical values are suggested along with tables of exact binomial probabilities

Statistical implications of pooling RNA samples for microarray experiments

BACKGROUND: Microarray technology has become a very important tool for studying gene expression profiles under various conditions. Biologists often pool RNA samples extracted from different subjects onto a single microarray chip to help defray the cost of microarray experiments as well as to correct for the technical difficulty in getting sufficient RNA from a single subject. However, the statistical, technical and financial implications of pooling have not been explicitly investigated. RESULTS: Modeling the resulting gene expression from sample pooling as a mixture of individual responses, we derived expressions for the experimental error and provided both upper and lower bounds for its value in terms of the variability among individuals and the number of RNA samples pooled. Using virtual pooling of data from real experiments and computer simulations, we investigated the statistical properties of RNA sample pooling. Our study reveals that pooling biological samples appropriately is statistically valid and efficient for microarray experiments. Furthermore, optimal pooling design(s) can be found to meet statistical requirements while minimizing total cost. CONCLUSIONS: Appropriate RNA pooling can provide equivalent power and improve efficiency and cost-effectiveness for microarray experiments with a modest increase in total number of subjects. Pooling schemes in terms of replicates of subjects and arrays can be compared before experiments are conducted