17 research outputs found

    Land Contract or Mortgage?

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    The use of land contracts in buying and selling farms is increasing in Iowa. The contract is basically different from the traditional deed and mortgage, and advantages and disadvantages should be weighed carefully

    Exploiting the labile site in dinuclear [Pd2L2]n+ metallo-cycles: multi-step control over binding affinity without alteration of core host structure

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    While Nature often controls supramolecular processes through regulation giving multiple levels of activity, synthetic metallosupramolecular systems have generally been binary (e.g. on/off) when they have control over molecular recognition events, and have often relied upon drastic chemical transformations or complete disassembly to enforce this control. We report here a new low symmetry ligand with a bidentate and a monodentate site (L). In combination with Pd2+, this ligand forms a [2 + 2] metallo-macrocycle, [Pd2L2L′2]n+, where L′ is the monodentate ancillary ligand that occupies the fourth and final coordination site of the metal ions. This assembly is structurally simple, but displays nuanced, multi-step binding affinity toward a neutral diplatinate guest employed for proof-of-concept. This complexity is introduced through varying the identity of L′, which can either be solvent (DMSO) or the halides chloride, bromide or iodide. The identity of L′ alters the cationic charge of the complex (neutral DMSO versus monoanionic halides) or otherwise influences the electron deficiency of the binding site of the host through varied strength of halide-ligand intra-molecular hydrogen bonding. Cycling between these different complexes was demonstrated, except for L′ = chloride which is non-reversible. This system therefore is able to interact with a platinate guest with four different graduations of affinity in response to stimuli, while still retaining the same simple core cationic structure. In addition to multi-setting binding affinity, we believe this is the first example of the use of variable intramolecular hydrogen bonding strength in switchable ancillary ligands to alter the electronic character and hence the π-π recognition characteristics of a metallosupramolecular host.DP would like to thank the ARC for a DECRA Fellowship, and the Royal Society of New Zealand for a Rutherford Postdoctoral Fellowship. BH would like to gratefully acknowledge the MBIE Catalyst Fund for a PhD scholarship. RV would like to thank the University of Otago for a PhD scholarship. The authors would like to thank the Australia National University, the University of Canterbury, the University of Otago, and the MacDiarmid Institute for additional funding. The authors acknowledge the contribution of the NeSI high performance computing facilities to the results of this research. New Zealand’s national facilities are provided by the New Zealand eScience Infrastructure and funded jointly by NeSI’s collaborator institutions and through the Ministry of Business, Innovation & Employment’s Research Infrastructure program. https://www.nesi.org.nz

    Pre-Release Consumption of Methyl Eugenol Increases the Mating Competitiveness of Sterile Males of the Oriental Fruit Fly, Bactrocera dorsalis, in Large Field Enclosures

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    The sterile insect technique may be implemented to control populations of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), when environmental concerns preclude widespread use of chemical attractants or toxicants. The goal of the present study was to evaluate whether the mating competitiveness of sterile B. dorsalis males could be increased via pre-release feeding on methyl eugenol. Males of the oriental fruit fly are strongly attracted to this plant-borne compound, which they ingest and use in the synthesis of the sex pheromone. Previous studies conducted in the laboratory and small field-cages have shown that males given methyl eugenol produce a more attractive pheromone for females and have a higher mating success rate than males denied methyl eugenol. Here, levels of egg sterility were compared following the release of wild-like flies and either methyl eugenol-fed (treated) or methyl eugenol-deprived (control) sterile males in large field enclosures at four over flooding ratios ranging from 5:1 to 60:1 (sterile: wild-like males). Treated sterile males were fed methyl eugenol for 1–4 h (depending on the over flooding ratio tested) 3 d prior to release. Eggs were dissected from introduced fruits (apples), incubated in the laboratory, and scored for hatch rate. The effect of methyl eugenol was most pronounced at lower over flooding ratios. At the 5:1 and 10:1 over flooding ratios, the level of egg sterility observed for treated, sterile males was significantly greater than that observed for control, sterile males. In addition, the incidence of egg sterility reported for treated sterile males at these lower over flooding ratios was similar to that noted for treated or control sterile males at the 30:1 or 60:1 over flooding ratios. This latter result, in particular, suggests that pre-release feeding on methyl eugenol allows for a reduction in the number of sterile flies that are produced and released, thus increasing the cost-effectiveness of the sterile insect technique

    Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir during Suppressive Antiretroviral Therapy

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    Background: Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men. Methods: ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells. Results: We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes. Conclusions: Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy

    The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial virus infection independent of TLR activation

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    Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. However, it is unclear why most primary RSV infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. Since RSV hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR) agonists influence RSVA2- GFP infection in human primary cells or cell lines. The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal when lipopeptides and virus were added simultaneously, whereas addition of Pam3CSK4 immediately after infection had no effect. We have identified two structurally related lipopeptides without TLR-signaling capacity that also modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and conclude that modulation of infection is independent of TLR activation. A similar TLR-independent enhancement of infection could also be demonstrated for wild-type RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its target cells. The Npalmitoylated cystein

    Genetic diversity fuels gene discovery for tobacco and alcohol use

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    Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

    Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir During Suppressive Antiretroviral Therapy.

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    BackgroundPersistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men.MethodsART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells.ResultsWe did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes.ConclusionsDifferences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy
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