Novel Approaches To Improve DNA Vaccine Induced Responses Against Difficult Infectious Disease Targets

Vaccines have significantly improved human health through decreasing morbidity and mortality associated with infectious diseases. Through the use of vaccines, we have seen the eradication of Small Pox and the control of numerous other diseases which once crippled the society. However, older vaccine technologies have not been successful in tackling many remaining infectious diseases including Human Immunodeficiency Virus (HIV), Malaria, Tuberculosis (TB), emerging diseases or therapeutically impacting cancer. Due to the complexity of these targets, novel vaccine platforms are needed. DNA vaccines were first reported in the early 1990s and demonstrated significant success in small animals. However, due to their lack of robust immunogenicity in large animals and human subjects, excitement was quickly tempered. After years of optimizations and improvements, DNA vaccines can now generate responses as high or higher than other vaccine platforms in these species. Here we explore some of the strength of DNA vaccine technology to improve vaccine-induced responses further. First, due to the ease of production and ability to formulate multiple plasmids into a single immunization, we explore the relationship between vaccine breadth and the coverage of induced responses. Formulations of multiple plasmids encoding the HIV-1 surface protein, Envelope, were able to induce superior responses compared to a single plasmid formulation. These responses were further improved by including small clusters of plasmids, limiting the diversity within a single immunization. We also explore the use of plasmid encoded immune adjuvants to enhance or tailor the vaccine responses. Two sets of adjuvants, mucosal chemokines and various forms of CD40L, display a range of adjuvanting effects and can increase protection against challenge. Overall, these improvements in DNA vaccine performance will progress the translational development of new studies aimed at impacting important, however, difficult infectious diseases

Vector Mosquito Surveillance Using Centers For Disease Control and Prevention Autocidal Gravid Ovitraps In San Antonio, Texas

Mosquito surveillance in large urban areas of the southern USA that border Mexico has become increasingly important due to recent transmission of Zika virus and chikungunya virus in the Americas as well as the continued threat of dengue and West Nile viruses. The vectors of these viruses, Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus, co-occur in residential areas, requiring vector control entities to deploy several different trap types, often expensive and labor-intensive, to surveil these ecologically different species. We evaluated the use of a single trap type, the US Centers for Disease Control and Prevention autocidal gravid ovitraps (AGOs), to monitor all 3 vector species across residential neighborhoods in San Antonio, TX, over 12 wk (epiweeks 24–35). Mosquito abundance was highest early in our surveillance period (epiweek 25) and was driven largely by Cx. quinquefasciatus. The AGOs collected significantly more Cx. quinquefasciatus than both Aedes species, with more Ae. aegypti collected than Ae. albopictus. The average number of Ae. aegypti captured per trap was consistent across most neighborhoods except for 2 areas where one had significantly the highest and the other with the lowest mosquitoes collected per trap. The average number of Ae. albopictus captured per trap varied with no clear pattern, and Cx. quinquefasciatus were trapped most often near forested hill country neighborhoods. These results indicate that AGOs are appropriate for detecting and tracking the relative abundance of Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus across a large and diverse urban landscape over time and therefore may be an inexpensive and streamlined option for vector surveillance programs in large cities

Genetic Elimination of Dengue Vector Mosquitoes

An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was engineered to have a repressible female-specific flightless phenotype. This strain circumvents the need for radiation-induced sterilization, allows genetic sexing resulting in male-only releases, and permits the release of eggs instead of adult mosquitoes. OX3604C males introduced weekly into large laboratory cages containing stable target mosquito populations at initial ratios of 8.5-10:1 OX3604C:target eliminated the populations within 10-20 weeks. These data support the further testing of this strain in contained or confined field trials to evaluate mating competitiveness and environmental and other effects. Successful completion of the field trials should facilitate incorporation of this approach into areawide dengue control or elimination efforts as a component of an integrated vector management strategy

Development of a Semi-Field System for Contained Field Trials With Aedes Aegypti in Southern Mexico

Development of new genetic approaches to either interfere with the ability of mosquitoes to transmit dengue virus or to reduce vector population density requires progressive evaluation from the laboratory to contained field trials, before open field release. Trials in contained outdoor facilities are an important part of this process because they can be used to evaluate the effectiveness and reliability of modified strains in settings that include natural environmental variations without releasing mosquitoes into the open field. We describe a simple and cost-effective semi-field system designed to study Aedes aegypti carrying a dominant lethal gene (fsRIDL) in semi-field conditions. We provide a protocol for establishing, maintaining, and monitoring stable Ae. aegypti population densities inside field cages

Adaptation of a microbial detection array as a monitoring tool revealed the presence 2 of mosquito-borne viruses and insect-specific viruses in field-collected mosquitoes

Several mosquito-borne diseases affecting humans are emerging or re-emerging in the United States. The early detection of pathogens in mosquito populations is essential to prevent and control the spread of these diseases. In this study, we tested the potential applicability of the Lawrence Livermore Microbial Detection Array (LLMDA) to enhance bio-surveillance by detecting microbes present in Aedes aegypti, Aedes albopictus and Culex mosquitoes that are major vector species globally, including in Texas. The sensitivity and reproducibility of the LLMDA was tested in mosquito samples spiked with different concentrations of dengue virus (DENV) revealing a detection limit of \u3e100 but \u3c1000 pfu/mL. Additionally, field-collected mosquitoes from Chicago, Illinois and College Station, Texas of known infection status (West Nile virus (WNV) and Culex flavivirus (CxFLAV) positive) were tested on the LLMDA to confirm its efficiency. Mosquito field samples of unknown infection status, collected in San Antonio, TX and the Lower Rio Grande Valley (LRGV), TX were run on the LLMDA and further confirmed by PCR or qPCR. The analysis of the field samples with the LLMDA revealed the presence of cell fusing agent virus (CFAV) in Ae. aegypti populations. Wolbachia was also detected in several of the field samples (Ae. albopictus and Culex spp.) by the LLMDA. Our findings demonstrated that the LLMDA can be used to detect multiple arboviruses of public health importance including viruses that belong to the Flavivirus, Alphavirus and Orthobunyavirus genera. Additionally, insect-specific viruses and bacteria were also detected from field-collected mosquitoes. Another strength of this array is its ability to detect multiple viruses in the same mosquito pool allowing for the detection of co-circulating pathogens in an area, and the identification of potential ecological associations between different viruses. This array can aid in the bio-surveillance of mosquito borne viruses circulating in specific geographical areas

Kate 2008 Spring

Each year, kate seeks to: explore ideas about normative gender, sex, and sexuality work against oppression and hierarchies of power in any and all forms serve as a voice for race and gender equity as well as queer positivity encourage the silent to speak and feel less afraid build a zine and community that we care about and trusthttps://digitalcommons.otterbein.edu/kate/1008/thumbnail.jp

The Grizzly, November 17, 2005

Morgan Tyler McKinney Christened in Bomberger • Brewer\u27s Festival • March of Dimes / A.I.R. Awards • Say Hello to Carmella Greco • Sexual Engineering • The Examined Life Brings Memories of CIE • Opinions: A Call for Justice: The Fight Against Satire at Ursinus; It\u27s Your Bed, So Make It; Life: The Eight o\u27Clock Spanish Class; Why This Liberal Supports Samuel Alito • Bears Advance to Final Four • Spirits Still High After Season Opening Losshttps://digitalcommons.ursinus.edu/grizzlynews/1700/thumbnail.jp

The Grizzly, October 13, 2005

Rain Dampens, But Fails to Quench, Family Day • UC Tuition Series Part 3: Financial Aid and Scholarships • All in the Timing Opens with Great Aplomb • Program Spotlight: International Film Festival • Internet Feud • Don Asher Speaks on Getting Into Grad School • Interview with The Abercrombie Couple • Texas Hold \u27Em Wins Over Ursinus Students • Why Run When You Can Walk? • Taking Care of an Embarrassing Problem • A New Band of Brothers Comes to Ursinus • Trail Travel • A Great Halloween Costume is Right Around the Corner • Child Development Expert Lectures • Atlantic Monthly\u27s James Fallows to Speak at Ursinus • Opinions: Look, Mom, No Hips!; Laughter is the Best Medicine; Cronyism; I Wonder How Long This One Will Last • Independent Film Producer Nadine Patterson to Speak at Ursinus • Baney Boots Bears Over Newport News • Field Hockey Ranked #1 in Nation • Women\u27s Rugby Drenches Lebanon Valleyhttps://digitalcommons.ursinus.edu/grizzlynews/1696/thumbnail.jp

Genetic association and characterization of FSTL5 in isolated clubfoot

ACKNOWLEDGEMENTS: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The authors thank the staff and participants of the ARIC study for their important contributions. Funding for GENEVA was provided by National Human Genome Research Institute grant U01HG004402 (E.Boerwinkle). We thank H. Hobbs and J. Cohen for contributing control samples for replication genotyping, Nadav Ahituv for sharing RNA-seq data for both bat and mouse embryonic limb buds, Tommy Hyatt for designing the custom genotyping assay, and members of the UT Southwestern Transgenic Core facility, including John Ritter, Mylinh Nguyen, and Robert Hammer. Publicly available mouse embryonic expression analysis results were provided online at https://oncoscape.v3.sttrcancer.org/atlas.gs.washington.edu.mouse.rna/landing (24). The authors acknowledge the contributions and support of the Center for Excellence in Clubfoot Research at Scottish Rite for Children, including Shawne Faulks and Kristhen Atala. Fstl5 mutant rats were produced by the NIH Mutant Rat Resource at UT Southwestern Medical Center (R24RR03232601, R24OD011108, R01HD036022, and (5R01HD053889). This study was supported by funding from the Scottish Rite for Children Research Fund (J.J.R.), Shriners Hospital for Children (J.T.H), and the National Institutes of Health award R01HD043342 (J.T.H.).Peer reviewedPostprin

Cold, clumpy accretion onto an active supermassive black hole

Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales. The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas. Recent theory and simulations instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds - a departure from the "hot mode" accretion model - although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z=0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma. Under the right conditions, thermal instabilities can precipitate from this hot gas, producing a rain of cold clouds that fall toward the galaxy's centre, sustaining star formation amid a kiloparsec-scale molecular nebula that inhabits its core. The observations show that these cold clouds also fuel black hole accretion, revealing "shadows" cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole in the galaxy centre, which serves as a bright backlight. Corroborating evidence from prior observations of warmer atomic gas at extremely high spatial resolution, along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it