Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 310-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 310-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with upstream ligands

Effectiveness of an HIV Prevention Program for Women Visiting Their Incarcerated Partners: The HOME Project

Having an incarcerated partner presents a unique HIV risk for women, particularly low-income women of color. We developed a population-specific risk reduction intervention for women visiting men in prison that was peer educator-based and included individual and community-level intervention components. Women who were assessed prior to the intervention period had a positive association between the number of unprotected penetrative intercourse (UPI) episodes prior to their partners’ incarceration and the number of UPI episodes following partners’ release from prison. However, this association was negated among women assessed during the intervention. Intervention participants also were more likely to be tested for HIV, to have partners who got tested, and to talk with their partners about significantly more HIV-related topics. Conducting intervention and evaluation activities with women visiting incarcerated men is feasible and is a useful model for reaching more at-risk women

Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1

We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1

Construction of high-resolution genetic maps of Zoysia matrella (L.) Merrill and applications to comparative genomic analysis and QTL mapping of resistance to fall armyworm

BACKGROUND: Zoysia matrella, widely used in lawns and sports fields, is of great economic and ecological value. Z. matrella is an allotetraploid species (2n = 4x = 40) in the genus zoysia under the subfamily Chloridoideae. Despite its ecological impacts and economic importance, the subfamily Chloridoideae has received little attention in genomics studies. As a result, limited genetic and genomic information are available for this subfamily, which have impeded progress in understanding evolutionary history of grasses in this important lineage. The lack of a high-resolution genetic map has hampered efforts to improve zoysiagrass using molecular genetic tools. RESULTS: We used restriction site-associated DNA sequencing (RADSeq) approach and a segregating population developed from the cross between Z. matrella cultivars ‘Diamond’ and ‘Cavalier’ to construct high-resolution genetic maps of Z. matrella. The genetic map of Diamond consists of 2,375 Single Nucleotide Polymorphism (SNP) markers mapped on 20 linkage groups (LGs) with a total length of 1754.48 cM and an average distance between adjacent markers at 0.74 cM. The genetic map of Cavalier contains 3,563 SNP markers on 20 LGs, covering 1824.92 cM, with an average distance between adjacent markers at 0.51 cM. A higher level of genome collinearity between Z. matrella and rice than that between Z. matrella and sorghum was revealed by comparative genomic analysis. Pairwise comparison revealed that two independent nested chromosome fusion events occurred after Z. matrella and sorghum split from a common ancestor. The high-resolution linkage maps were applied into mapping QTLs associated with fall armyworm (FAW) resistance and six loci located on LGs 8 and 20 were detected to be significantly associated with FAW resistance. CONCLUSION: The high-resolution linkage maps provide anchor points for comparative genomics analysis between Z. matrella and other grass species. Our comparative genomic analysis suggested that the chromosome number reduction from 12 to 10 had occurred independently via a single-step in the subfamilies Chloridoideae and Panicoideae. The high-resolution genetic maps provide an essential framework for mapping QTLs associated with economically and agronomically important traits. The major QTLs mapped on LG8 of the Cavalier map provide a starting point for cloning FAW resistance genes and further studies for a better understanding of FAW resistance in zoysiagrass. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2969-7) contains supplementary material, which is available to authorized users