Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences.

External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA. In MCMV-infected cells, the variant reduced mCSP expression by 92% and inhibited viral growth by 8,000-fold. In MCMV-infected mice hydrodynamically transfected with EGS-expressing constructs, the EGS variant was more effective in reducing mCSP expression, decreasing viral production, and enhancing animal survival than the EGS originating from a natural tRNA. These results provide direct evidence that engineered EGS variants with higher targeting activity in vitro are also more effective in reducing gene expression in animals. Furthermore, our findings imply the possibility of engineering potent EGS variants for therapy of viral infections

Polysaccharide-based nanomedicines for cancer immunotherapy: a review

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.info:eu-repo/semantics/publishedVersio

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE

Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo

CGMP: cloud-assisted green multimedia processing

With continued advancements of mobile computing and communications, emerging novel multimedia services and applications have attracted lots of attention and been developed for mobile users, such as mobile social network, mobile cloud medical treatment, mobile cloud game. However, because of limited resources on mobile terminals, it is of great challenge to improve the energy efficiency of multimedia services. In this paper, we propose a cloud-assisted green multimedia processing architecture (CGMP) based on mobile cloud computing. Specifically, the tasks of multimedia processing with energy-extensive consumption can be offloaded to the cloud, and the face recognition algorithm with improved principal component analysis and nearest neighbor classifier is realized on CGMP based cloud platform. Experimental results show that the proposed scheme can effectively save the energy consumption of the equipment

9 W average power, 150 kHz repetition rate diamond Raman laser at 1519 nm, pumped by a Yb fibre amplifier

Commercially available pulsed fibre lasers at ~1.5 μm have many uses in imaging, defense, communications and light radar (LIDAR) [1]. For 3D scanning LIDAR, higher signal-to-noise ratio requires lasers with high average power and high pulse repetition rate (ideally several MHz) for faster scanning rate, whereas to improve distance resolution requires pulse durations <10 ns [2,3]. One limitation of the pulsed fibre lasers at ~1.5 μm is scaling to high average powers [4]. Raman frequency conversion of high average power fibre master oscillator power amplifier (MOPA) systems at ~1 μm is a potential alternative. The large Raman shift and Raman gain of diamond allows two-stage Raman conversion to ~1.5 μm for ~1 μm pumping [5]. Excellent thermal properties make diamond suitable for high average powers [6]. Much work has been done on conversion of 1.064 μm lasers to 1.485 μm using diamond [7]; however, the “eye-safety” requirements for LIDAR typically call for wavelengths above 1.5 μm, due to the order of magnitude higher Maximum Permissible Exposure limit [8]. Developing such a diamond Raman laser (DRL) was the major motivation for this research

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

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