A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice

published_or_final_versio

The α2δ-like Protein Cachd1 Increases N-type Calcium Currents and Cell Surface Expression and Competes with α2δ-1

Voltage-gated calcium channel auxiliary α2δ subunits are important for channel trafficking and function. Here, we compare the effects of α2δ-1 and an α2δ-like protein called Cachd1 on neuronal N-type (CaV2.2) channels, which are important in neurotransmission. Previous structural studies show the α2δ-1 VWA domain interacting with the first loop in CaV1.1 domain-I via its metal ion-dependent adhesion site (MIDAS) motif and additional Cache domain interactions. Cachd1 has a disrupted MIDAS motif. However, Cachd1 increases CaV2.2 currents substantially (although less than α2δ-1) and increases CaV2.2 cell surface expression by reducing endocytosis. Although the effects of α2δ-1 are abolished by mutation of Asp122 in CaV2.2 domain-I, which mediates interaction with its VWA domain, the Cachd1 responses are unaffected. Furthermore, Cachd1 co-immunoprecipitates with CaV2.2 and inhibits co-immunoprecipitation of α2δ-1 by CaV2.2. Cachd1 also competes with α2δ-1 for effects on trafficking. Thus, Cachd1 influences both CaV2.2 trafficking and function and can inhibit responses to α2δ-1

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Luminescent Organic–Inorganic Hybrids of Functionalized Mesoporous Silica SBA-15 by Thio-Salicylidene Schiff Base

Novel organic–inorganic mesoporous luminescent hybrid material N, N′-bis(salicylidene)-thiocarbohydrazide (BSTC-SBA-15) has been obtained by co-condensation of tetraethyl orthosilicate and the organosilane in the presence of Pluronic P123 surfactant as a template. N,N′-bis(salicylidene)-thiocarbohydrazide (BSTC) grafted to the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TESPIC) was used as the precursor for the preparation of mesoporous materials. In addition, for comparison, SBA-15 doped with organic ligand BSTC was also synthesized, denoted as BSTC/SBA-15. This organic–inorganic hybrid material was well-characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy (HRTEM), and photoluminescence spectra, which reveals that they all have high surface area, uniformity in the mesostructure. The resulting materials (BSTC-SBA-15 and BSTC/SBA-15) exhibit regular uniform microstructures, and no phase separation happened for the organic and the inorganic compounds was covalently linked through Si–O bonds via a self-assemble process. Furthermore, the two materials have different luminescence range: BSTC/SBA-15 presents the strong dominant green luminescence, while BSTC-functionalized material BSTC-SBA-15 shows the dominant blue emission

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size

Longitudinal seroepidemiologic study of the 2009 pandemic influenza A (H1N1) infection among health care workers in a children's hospital

<p>Abstract</p> <p>Background</p> <p>To probe seroepidemiology of the 2009 pandemic influenza A (H1N1) among health care workers (HCWs) in a children's hospital.</p> <p>Methods</p> <p>From August 2009 to March 2010, serum samples were drawn from 150 HCWs in a children's hospital in Taipei before the 2009 influenza A (H1N1) pandemic, before H1N1 vaccination, and after the pandemic. HCWs who had come into direct contact with 2009 influenza A (H1N1) patients or their clinical respiratory samples during their daily work were designated as a high-risk group. Antibody levels were determined by hemagglutination inhibition (HAI) assay. A four-fold or greater increase in HAI titers between any successive paired sera was defined as seroconversion, and factors associated with seroconversion were analyzed.</p> <p>Results</p> <p>Among the 150 HCWs, 18 (12.0%) showed either virological or serological evidence of 2009 pandemic influenza A (H1N1) infection. Of the 90 unvaccinated HCWs, baseline and post-pandemic seroprotective rates were 5.6% and 20.0%. Seroconversion rates among unvaccinated HCWs were 14.4% (13/90), 22.5% (9/40), and 8.0% (4/50) for total, high-risk group, and low-risk group, respectively. Multivariate analysis revealed being in the high-risk group is an independent risk factor associated with seroconversion.</p> <p>Conclusion</p> <p>The infection rate of 2009 pandemic influenza A (H1N1) in HCWs was moderate and not higher than that for the general population. The majority of unvaccinated HCWs remained susceptible. Direct contact of influenza patients and their respiratory samples increased the risk of infection.</p