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Silver Spring, MD, United States

Lindroth E.,WRAIR | Hunt T.E.,Haskell Agricultural Laboratory | Skoda S.R.,Knipling Bushland Us Livestock Insects Research Laboratory | Culy M.D.,Dow AgroSciences | And 2 more authors.
Annals of the Entomological Society of America | Year: 2012

The western bean cutworm, Striacosta albicosta (Smith), is a secondary pest of maize (Zea mays L.) and dry beans (Phaseolus vulgaris L.) in the western United States. Recently, this insect has undergone a major territory expansion into the eastern United States and has become a pest throughout much of the Corn Belt. This study was instigated to examine the population genetics of this pest to facilitate control and resistance management, as well as to shed light on the current habitat expansion. S. albicosta individuals were collected from 24 different locations across the traditional and expanded range and amplified fragment length polymorphism analysis was conducted to assess genetic variability. In total, 90 markers were analyzed, encompassing >90% of genetic variation. Gst across all locations was moderately high (Gst = 0.5032). AMOVA analysis revealed that the majority of genetic variation was within locations (54%) and among locations within groups (45%) indicating genetic differentiation of subpopulations. The Mantel test revealed no correlation between geographic and genetic distance (n = 548; r = 0.0045; P = 0.4350). Locations sampled in the eastern United States did not exhibit any reduction in genetic variation in comparison to locations sampled in the western United States, so we conclude that no bottleneck event has occurred with this territory expansion. © 2012 Entomological Society of America. Source

Young C.,Naval Undersea Medical Institute | Oladipo O.,20 John Paul Jones Circle | Frasier S.,United Road Services | Putko R.,United Road Services | And 2 more authors.
Military Medicine | Year: 2012

A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, β-alanine, creatine monohydrate, and L-arginine α-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine. The product has no readily apparent disclaimer or warning regarding the risks or lack of data regarding the components. Jack3d is sold as a nutritional supplement and is therefore not subject to same FDA regulation and scrutiny that a pharmaceutical receives. The potential adverse effect was reported to the FDA via MedWatch in accordance with the recently passed Dietary Supplement and Nonprescription Drug Consumer Protection Act. Source

Bergmann-Leitner E.S.,U.S. Army | Hosie H.,U.S. Army | Trichilo J.,Vital Probes, Inc. | DeRiso E.,U.S. Army | And 10 more authors.
Frontiers in Immunology | Year: 2013

Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide a strong danger signal thus circumventing the requirement for potent extraneous adjuvants. E. coli expressing malarial antigens resulted in the induction of either Th1 or Th2 biased responses that were dependent on both antigen and sub-cellular localization. Some of these constructs induced higher quality humoral responses compared to recombinant protein and most importantly they were able to induce sterile protection against sporozoite challenge in a murine model of malaria. In light of these encouraging results, two major Plasmodium falciparum pre-erythrocytic malaria vaccine targets, the Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS) fused to the Maltose-binding protein in the periplasmic space and the Circumsporozoite Protein (CSP) fused to the Outer membrane (OM) protein A in the OM were expressed in a clinically relevant, attenuated Shigella strain (Shigella flexneri 2a). This type of live-attenuated vector has previously undergone clinical investigations as a vaccine against shigellosis. Using this novel delivery platform for malaria, we find that vaccination with the whole-organism represents an effective vaccination alternative that induces protective efficacy against sporozoite challenge. Shigella GeMI-Vax expressing malaria targets warrant further evaluation to determine their full potential as a dual disease, multivalent, self-adjuvanting vaccine system, against both shigellosis, and malaria. © 2013 Bergmann-Leitner, Hosie, Trichilo, DeRiso, Ranallo, Alefantis, Savranskaya, Grewal, Ockenhouse, Venkatesan, DelVecchio and Angov. Source

Paranavitana C.,WRAIR | Zelazowska E.,WRAIR | Dasilva L.,U.S. Army | Pittman P.R.,U.S. Army | Nikolich M.,WRAIR
Journal of Interferon and Cytokine Research | Year: 2010

To determine whether cytokines and T-cell subsets other than Th1 cells contribute to secondary immune responses against Francisella species, we investigated production of Th17-associated cytokines IL-17 and IL-22 in a recall response to Francisella tularensis. Peripheral blood mononuclear cells (PBMCs) from volunteers previously immunized with the F. tularensis live vaccine strain (LVS) were stimulated in vitro with bacterial lysates of LVS or a nonpathogenic type A B38 strain. Gene expression analysis by real-time PCR showed that IL-17 and IL-22 transcripts were induced in immune PBMCs at a significantly higher level than in cells from nonvaccinated volunteers stimulated with LVS or B38 antigens at 24?h. In addition, we detected both cell-associated and secreted IL-22 at 24?h after stimulation and IL-17 at 72?h post-stimulation. Intracellular IL-22 and IL-17 were observed in memory CD4+ cells and less in memory CD8+ cells. These findings suggest that Th17 responses in addition to the Th1 response may play an important role in adaptive immunity against Francisella. © Mary Ann Liebert, Inc. Source

Stoddard M.B.,WRAIR | Stoddard M.B.,University of Alabama at Birmingham | Pinto V.,WRAIR | Keiser P.B.,WRAIR | Zollinger W.,WRAIR
Clinical and Vaccine Immunology | Year: 2010

Bacterial endotoxin interacts with the human immune system via complex immunological pathways. The evaluation of endotoxicity is important in the development of safe vaccines and immunomodulatory therapeutics. The Limulus amebocyte lysate (LAL) assay is generally accepted by the FDA for use for the quantification of lipopolysaccharide (LPS), while the rabbit pyrogen test (RPT) is used to estimate pyrogenicity during early development and production. Other in vitro assays, such as cytokine release assays with human whole blood (WB) or peripheral blood mononuclear cells (PBMCs), have also been used and may better estimate the human immunological response to products containing novel LPS molecules. In this study, WB and PBMC interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) release assays were used to estimate the endotoxic activities of purified LPS and native outer membrane vesicle (NOMV) vaccines derived from wild-type (hexa-acylated lipid A) and genetically detoxified (penta- and tetra-acylated lipid A) group B Neisseria meningitidis. A method for quantification of the differences in endotoxicity observed in the WB and PBMC assays is elucidated. The LAL assay was shown to be relatively insensitive to lipid A variations, and the RPT was less sensitive than the cytokine release assay with WB. The IL-6 and TNF-α assays with WB but not the assays with PBMCs distinguished between vaccines containing LPS from penta- and tetra-acylated strains. The high degree of sensitivity of the WB system to LPS variations and the presumed relevance of the use of human tissues to predict toxicity in humans suggest that this assay may be particularly well suited for the safety evaluation of vaccines and therapeutics containing acylation variants of LPS. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source

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