Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.

Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36p(-)), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36p(-) sporozoites abort during development within the hepatocyte. Immunization with p36p(-) sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36p(-) sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36p(-) sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine.

Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Protective services for adults : a guide to exemplary practice in states providing protective services to adults in OHDS programs /

"Spring 1982."

Limited-use chemical protective clothing for EPA Superfund activities /

Mode of access: Internet.

Manual of protective action guides and protective actions for nuclear incidents.

"EPA 520/1-75-001-A"--Cover.

Evaluation of commercially available laser protective eyeware /

Mode of access: Internet.

Personal protective equipment.

"OSHA 3077."

Development of criteria and test methods for eye and face protective devices /

Mode of access: Internet.

Sources of statistical data: textiles & apparel

"Original guide published in 1964."

The C.H.P.A. cook book : choice recipes from the members and friends of Cleveland Health Protective Ass'n /

Includes household hints; samples of menus; table of seasons for foodstuffs; some recipes include wine or liquor as an ingredient; recipes for English, French, and Cuban dishes. Sample recipes: Roast goose, Codfish on toast (Cuban style), Gingerbread pudding.

Performance evaluation of respiratory protective equipment used in paint spraying operations /

Mode of access: Internet.

Protect labor : an address to the working men by the editor of "America" ; to which are appended statements showing the increase of manufacturing industry and wealth under a protective tariff, rates of wages in Europe as compared with the United States, etc. /

Mode of access: Internet.

School bus occupant-retrofit protective materials. Volume I: summary report. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

School bus occupant-retrofit protective materials. Volume II: technical report. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Material development study for a hazardous chemical protective clothing outfit : final report /

"Report no. CG-D-58-80."