A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits Broad Neutralizing Antibody Response in Pigs.

BACKGROUND Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in Southeast Asia. Vaccination of domestic pigs has been suggested as a "one health" strategy to reduce viral disease transmission to humans. The efficiency of two lentiviral TRIP/JEV vectors expressing the JEV envelope prM and E glycoproteins at eliciting protective humoral response was assessed in a mouse model and piglets. METHODOLOGY/PRINCIPAL FINDINGS A gene encoding the envelope proteins prM and E from a genotype 3 JEV strain was inserted into a lentiviral TRIP vector. Two lentiviral vectors TRIP/JEV were generated, each expressing the prM signal peptide followed by the prM protein and the E glycoprotein, the latter being expressed either in its native form or lacking its two C-terminal transmembrane domains. In vitro transduction of cells with the TRIP/JEV vector expressing the native prM and E resulted in the efficient secretion of virus-like particles of Japanese encephalitis virus. Immunization of BALB/c mice with TRIP/JEV vectors resulted in the production of IgGs against Japanese encephalitis virus, and the injection of a second dose one month after the prime injection greatly boosted antibody titers. The TRIP/JEV vectors elicited neutralizing antibodies against JEV strains belonging to genotypes 1, 3, and 5. Immunization of piglets with two doses of the lentiviral vector expressing JEV virus-like particles led to high titers of anti-JEV antibodies, that had efficient neutralizing activity regardless of the JEV genotype tested. CONCLUSIONS/SIGNIFICANCE Immunization of pigs with the lentiviral vector expressing JEV virus-like particles is particularly efficient to prime antigen-specific humoral immunity and trigger neutralizing antibody responses against JEV genotypes 1, 3, and 5. The titers of neutralizing antibodies elicited by the TRIP/JEV vector are sufficient to confer protection in domestic pigs against different genotypes of JEV and this could be of a great utility in endemic regions where more than one genotype is circulating.

Bufferless Compression of Asynchronously Sampled ECG Signals in Cubic Hermitian Vector Space.

Asynchronous level crossing sampling analog-to-digital converters (ADCs) are known to be more energy efficient and produce fewer samples than their equidistantly sampling counterparts. However, as the required threshold voltage is lowered, the number of samples and, in turn, the data rate and the energy consumed by the overall system increases. In this paper, we present a cubic Hermitian vector-based technique for online compression of asynchronously sampled electrocardiogram signals. The proposed method is computationally efficient data compression. The algorithm has complexity O(n), thus well suited for asynchronous ADCs. Our algorithm requires no data buffering, maintaining the energy advantage of asynchronous ADCs. The proposed method of compression has a compression ratio of up to 90% with achievable percentage root-mean-square difference ratios as a low as 0.97. The algorithm preserves the superior feature-to-feature timing accuracy of asynchronously sampled signals. These advantages are achieved in a computationally efficient manner since algorithm boundary parameters for the signals are extracted a priori.

Interstellar neutral helium in the heliosphere from Interstellar Boundary Explorer observations. III. Mach number of the flow, velocity vector, and temperature from the first six years of measurements

We analyzed observations of interstellar neutral helium (ISN He) obtained from the Interstellar Boundary Explorer (IBEX) satellite during its first six years of operation. We used a refined version of the ISN He simulation model, presented in the companion paper by Sokol et al. (2015b), along with a sophisticated data correlation and uncertainty system and parameter fitting method, described in the companion paper by Swaczyna et al. We analyzed the entire data set together and the yearly subsets, and found the temperature and velocity vector of ISN He in front of the heliosphere. As seen in the previous studies, the allowable parameters are highly correlated and form a four-dimensional tube in the parameter space. The inflow longitudes obtained from the yearly data subsets show a spread of similar to 6 degrees, with the other parameters varying accordingly along the parameter tube, and the minimum chi(2) value is larger than expected. We found, however, that the Mach number of the ISN He flow shows very little scatter and is thus very tightly constrained. It is in excellent agreement with the original analysis of ISN He observations from IBEX and recent reanalyses of observations from Ulysses. We identify a possible inaccuracy in the Warm Breeze parameters as the likely cause of the scatter in the ISN He parameters obtained from the yearly subsets, and we suppose that another component may exist in the signal or a process that is not accounted for in the current physical model of ISN He in front of the heliosphere. From our analysis, the inflow velocity vector, temperature, and Mach number of the flow are equal to lambda(ISNHe) = 255 degrees.8 +/- 0 degrees.5, beta(ISNHe) = 5 degrees.16 +/- 0 degrees.10, T-ISNHe = 7440 +/- 260 K, nu(SNHe) = 25.8 +/- 0.4 km s(-1), and M-ISNHe = 5.079 +/- 0.028, with uncertainties strongly correlated along the parameter tube.

The Runge0Lenz Vector (continued)

We continue our discussion of the Runge-Lenz vector in a quantum mechanical context. The traditional form of the Runge-Lenz vector is obtained, and the commutation relations between the Runge-Lenz vector, the Hamiltonian, and the Angular Momentum are obtained using Maple.

The biologic and signaling effects of Tiam1 overexpression in colorectal carcinoma

Cellular migration is essential to many normal cellular processes. In tumor cells, aberrant activation of the normal pathways regulating migration is one of the critical steps in the development of metastasis. Previously, I demonstrated for the first time that overexpression of Tiam1, a guanine nucleotide exchange factor (GNEF) for small G proteins in the Rho family, could alter migration in colorectal tumor cells. ^ This dissertation focuses on the roles of Tiam1 in promoting cell migration, survival, and metastasis of colorectal carcinoma cells, utilizing the model system I developed. To determine the in vivo phenotype of the migratory cell lines, athymic nude mice were injected with cells into the orthotopic site. Several of the mice injected with cells of increased migratory potential had metastases. Thus, the in vitro selection for increased migration resulted in increased metastatic potential in vivo, and therefore, the Tiam1-overexpressing cells provide a model to examine signal transduction pathways important to this process. ^ To examine effects of Tiam1 signaling on small G proteins critical to cellular functions associated with migration, I examined the activation status of the small G proteins Rac, Rho, and Cdc42. The cells of increased migratory potential have increased GTP-bound Rac and Rho, compared to control SW480 cells. Cells that overexpress Tiam1 are more migratory and are resistant to detachment-induced death, or anoikis. To determine which effects and phenotypes were Tiam1-specific, we utilized siRNA to downregulate Tiam1 expression. These results demonstrate that Tiam1 is sufficient but not required for the migration of colorectal carcinoma cells in our model system, and that the biologically selected cells have additional changes that promote migration besides the increase in Tiam1. I also show that Tiam1 protects colorectal carcinoma cells from detachment-induced death, but is not required for anoikis resistance in the biologically selected migratory cells. ^ In summary, my studies demonstrate a heretofore-unknown regulator of phenotypes critical to the development of colorectal carcinoma metastases, overexpression of Tiam1. Understanding the mechanism by which Tiam1 contributes to cellular migration and metastasis is crucial to developing desperately needed new therapies for colorectal carcinoma. ^

Perspectives on the public health implications of global climate change and the epidemiology of vector-borne disease

Global climate change is becoming an increasing concern among the public health community. Some researchers believe the earth is rapidly undergoing changes in temperature, sea level, population movement, and extreme weather phenomenon. With these geographic, meteorological, and social changes come increased threats to human health. One of these threats is the spread of vector-borne infectious diseases. The changes mentioned above are believed to contribute to increased arthropod survival, transmission, and habitation. These changes, in turn, lead to increased incidence among neighboring human populations. It is also argued that human action may play more of a role than climate change. This systematic review served to determine whether or not climate change poses a significant risk to human exposure and increased incidence of vector-borne disease. ^

TRANSOVARIAL TRANSMISSION OF YELLOW FEVER VIRUS BY A SYLVATIC VECTOR, HAEMAGOGUS EQUINUS (THEOBALD)

The potential of a sylvatic vector to act as reservoir of yellow fever virus was assessed in Haemagogus equinus (Theobald). Mosquitoes from the Maje'75 laboratory colony and a Panamanian human isolated strain of yellow fever virus were used. Female mosquitoes infected with yellow fever virus had a minimum transovarial transmission rate of 1:5745. This is the first time transovarial transmission of yellow fever virus has been demonstrated in a New World sylvatic vector. Transovarial transmission of yellow fever virus in this sylvatic mosquito species may be an alternative mechanism for biological survival of the virus during adverse periods or in the absence of susceptible vertebrate hosts. ^

Experimental evaluation of seaweeds as a vector for microplastics into marine food webs, supplementary material

The ingestion of microplastics has been shown for a great variety of marine organisms. However, benthic marine mesoherbivores such as the common periwinkle Littorina littorea have been largely disregarded in studies about the effects of microplastics on the marine biota, probably because the pathway for microplastics to this functional group of organisms was not obvious. In laboratory experiments we showed that the seaweed Fucus vesiculosus retains suspended microplastics on its surface. The numbers of microplastics that adhered to the algae correlated with the concentrations of suspended particles in the water. In choice feeding assays L. littorea did not distinguish between algae with adherent microplastics and clean algae without microplastics, indicating that the snails do not recognize solid nonfood particles in the submillimeter size range as deleterious. In periwinkles that were feeding on contaminated algae, microplastics were found in the stomach and in the gut. However, no microplastics were found in the midgut gland, which is the principle digestive organ of gastropods. Microplastics in the fecal pellets of the periwinkles indicate that the particles do not accumulate rapidly inside the animals but are mostly released with the feces. Our results provide the first evidence that seaweeds may represent an efficient pathway for microplastics from the water to marine benthic herbivores.