다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

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Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

/pdf/circular-rnas-are-a-large-class-of-animal-rnas-with-3ah6n8c4c0.pdf

Circular RNAs are a large class of animal RNAs with regulatory potency

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

Natural RNA circles function as efficient microRNA sponges

L'invention concerne des methodes et des trousses pour detecter plusieurs sequences polynucleotidiques indiquant un pronostic sombre de B-CLL. Tous les polynucleotides sont transcrits a partir d'une zone 12p21-22 du chromosome humain. La plupart de ces polynucleotides ne codent pas des grands polypeptides, mais codent de petits peptides, ils peuvent fonctionner en tant qu'ARN. Quatre polynucleotides codent une nouvelle proteine, qui, dans un mode de realisation prefere de l'invention, peut etre utilisee en tant que cytokine, de preference en tant qu'interleukine. En outre, l'invention concerne des methodes et des compositions de traitement de B-CLL, en particulier B-CLL a pronostic sombre.

Methodes et trousses pour le diagnostic et le traitement de la leucemie lymphoide chronique de cellule b (b-cll)

Magnetic Correlations in Uranium-Platinum (UPt3) and Uranium-Thorium-Platinum (U1-xThxPt3)

The characterization of alternatively spliced RNA is a frequently performed task in the molecular biology laboratory. Several methods have been established to characterize specific transcripts, of which microarrays, northern analysis, RT-PCR and nuclease protection assays are the most frequently performed methods in the laboratory. Here, we describe the analysis of alternatively spliced RNA by using 5(')-end labelled DNA oligonucleotide probes and S1 nuclease. The method is sensitive, allowing detection of as little as a few hundred femtograms of a specific RNA, and useful for the quantitation of alternatively spliced mRNA isoforms. Because of its insensitivity towards RNA secondary structures and partially degraded RNA, it may perform better in the quantitation of RNA than northern analysis or RT-PCR, especially when long transcripts are studied.

S1 nuclease analysis of alternatively spliced mRNA.

The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across the time of cortical folding. These miRNAs were found to target Doublecortin (DCX), known to be involved in neuron migration during cortical folding of gyrencephalic brains. In vivo modulation of miRNA expression in mouse embryos confirmed that miR-34c and miR-204 can control neuronal migration and cortical morphogenesis, presumably by posttranscriptional regulation of DCX.

/pdf/cortical-morphogenesis-during-embryonic-development-is-3z937bja6v.pdf

Cortical Morphogenesis during Embryonic Development Is Regulated by miR-34c and miR-204.

Recent successes in clinical trials have provided important proof of concept that small interfering RNAs indeed constitute a new promising class of therapeutics. Although great efforts are still needed to ensure efficient means of delivery in vivo, the siRNA molecule itself has been successfully engineered by chemical modification to meet initial challenges regarding specificity, stability and immunogenicity. To date, a great wealth of siRNA architectures and types of chemical modification are available for promoting safe siRNA mediated gene silencing in vivo and, consequently, the choice of design and modification types can be challenging to individual experimenters. Here we review the literature and devise how to improve siRNA performance by structural design and specific chemical modification to ensure potent and specific gene silencing without unwarranted side effects and hereby complement the ongoing efforts to improve cell targeting and delivery by other carrier molecules.

/pdf/development-of-therapeutic-grade-small-interfering-rnas-by-euxcpqenx9.pdf

Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering.

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