20 research outputs found

    Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response

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    Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria. © 2014 Pernas et al

    Self-Reported Interest to Participate in a Health Survey if Different Amounts of Cash or Non-Monetary Incentive Types Were Offered

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    The objective of this study was to assess monetary and non-monetary factors that can influence the decision to participate in a future health survey. A questionnaire was administered to eligible, low-income participants (n = 1502) of the 2012 Los Angeles County Health and Nutrition Examination Survey (LAHANES-II). Multivariable regression analyses were performed to describe factors potentially associated with future intent to participate in similar survey designs. The results of the survey suggest that, overall, female participants had a greater interest in participating under a variety of incentive scenarios. Compared to the 25-34 age group, older participants (35-44, 45-84) reported more interest to participate if 10cash[prepaidgift/debitcard],acouponforproduct/travel,orasmallitem[e.g.,granolabar,tshirt,pen]wasoffered,whereasyoungerparticipants(1824)reportedgreaterinterestfor10 cash [prepaid gift/debit card], a coupon for product/travel, or a small item [e.g., granola bar, t-shirt, pen] was offered, whereas younger participants (18-24) reported greater interest for 25 cash or a coupon for product/travel. Non-Whites, when compared to Whites/Non-Hispanics, reported greater interest to participate if any of the incentives was offered. High school graduates, when compared to those with some college education, reported greater interest to participate if $10 cash, a small item, or a lottery ticket was offered. Presence of two or more chronic conditions increased interest while concerns about participation in LAHANES-II was associated with reduced interest to participate in future health-related surveys. The results suggest that both incentives and non-monetary considerations (e.g., personal concerns about participating and individual level characteristics) can influence the decision to participate in health-related surveys and offer insights into strategies that can improve response rates for these assessments that are often used to inform community planning
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