Richmondcallesen6271

A plague vaccine with a fusion cassette of YscF, F1, and LcrV encoding genes in an adenovirus-5 vector (rAd5-YFV) is evaluated for efficacy and immune responses in mice. Two doses of the vaccine provides 100% protection when administered intranasally against challenge with Yersinia pestis CO92 or its isogenic F1 mutant in short- or long- term immunization in pneumonic/bubonic plague models. The corresponding protection rates drop in rAd5-LcrV monovalent vaccinated mice in plague models. The rAd5-YFV vaccine induces superior humoral, mucosal and cell-mediated immunity, with clearance of the pathogen. Immunization of mice with rAd5-YFV followed by CO92 infection dampens proinflammatory cytokines and neutrophil chemoattractant production, while increasing Th1- and Th2-cytokine responses as well as macrophage/monocyte chemo-attractants when compared to the challenge control animals. This is a first study showing complete protection of mice from pneumonic/bubonic plague with a viral vector-based vaccine without the use of needles and the adjuvant.Sacred lotus (Nelumbo nucifera, or lotus) is one of the most widely grown aquatic plant species with important uses, such as in water gardening and in vegetable and herbal medicine. A public genomic database of lotus would facilitate studies of lotus and other aquatic plant species. Here, we constructed an integrative database the Nelumbo Genome Database (NGD, http//nelumbo.biocloud.net ). This database is a collection of the most updated lotus genome assembly and contains information on both gene expression in different tissues and coexpression networks. In the NGD, we also integrated genetic variants and key traits from our 62 newly sequenced lotus cultivars and 26 previously reported cultivars, which are valuable for lotus germplasm studies. As applications including BLAST, BLAT, Primer, Annotation Search, Variant and Trait Search are deployed, users can perform sequence analyses and gene searches via the NGD. Overall, the valuable genomic resources provided in the NGD will facilitate future studies on population genetics and molecular breeding of lotus.Alternative splicing relies on the combinatorial recruitment of splicing regulators to specific RNA binding sites. Chromatin has been shown to impact this recruitment. However, a limited number of histone marks have been studied at a global level. AM1241 concentration In this work, a machine learning approach, applied to extensive epigenomics datasets in human H1 embryonic stem cells and IMR90 foetal fibroblasts, has identified eleven chromatin modifications that differentially mark alternatively spliced exons depending on the level of exon inclusion. These marks act in a combinatorial and position-dependent way, creating characteristic splicing-associated chromatin signatures (SACS). In support of a functional role for SACS in coordinating splicing regulation, changes in the alternative splicing of SACS-marked exons between ten different cell lines correlate with changes in SACS enrichment levels and recruitment of the splicing regulators predicted by RNA motif search analysis. We propose the dynamic nature of chromatin modifications as a mechanism to rapidly fine-tune alternative splicing when necessary.The nonlinear Hall effect due to Berry curvature dipole (BCD) induces frequency doubling, which was recently observed in time-reversal-invariant materials. Here we report novel electric frequency doubling in the absence of BCD on a surface of the topological insulator Bi2Se3 under zero magnetic field. We observe that the frequency-doubling voltage transverse to the applied ac current shows a threefold rotational symmetry, whereas it forbids BCD. One of the mechanisms compatible with the symmetry is skew scattering, arising from the inherent chirality of the topological surface state. We introduce the Berry curvature triple, a high-order moment of the Berry curvature, to explain skew scattering under the threefold rotational symmetry. Our work paves the way to obtain a giant second-order nonlinear electric effect in high mobility quantum materials, as the skew scattering surpasses other mechanisms in the clean limit.The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer's disease (AD) as it potently suppresses the aggregation of amyloid β (Aβ); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear. The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Aβ and phosphorylated tau accumulation, and improved cognitive function in the 3 × Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation. Feeding with RA exerted an anti-inflammatory effect not only in the central nervous system but also in the periphery. Downregulation of the JNK signaling pathway in hippocampus may be a potential mechanism underlying the inhibition of progression of pathology and cognitive deficit by RA feeding.The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells. The aim of the present study was to develop a human-compatible formulation of the PfCyRPA vaccine candidate and confirming its activity in preclinical studies. Recombinant PfCyRPA expressed in HEK 293 cells was chemically coupled to phosphoethanolamine and then incorporated into the membrane of unadjuvanted influenza virosomes approved as antigen delivery system for humans. Laboratory animals were immunised with the virosome-based PfCyRPA vaccine to determine its immunogenic properties and in particular, its capacity to elicit parasite binding and growth-inhibitory antibodies.