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

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

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Modern Applied Statistics With S

Translation termination is the final step in protein biosynthesis when the synthesized polypeptide is released from the ribosome. Understanding this complex process is important for treatment of many human disorders caused by nonsense mutations in important genes. Here, we present a new method for the analysis of translation termination rate in cell-free systems, CTELS (for C-terminally extended luciferase-based system). This approach was based on a continuously measured luciferase activity during in vitro translation reaction of two reporter mRNA, one of which encodes a C-terminally extended luciferase. This extension occupies a ribosomal polypeptide tunnel and lets the completely synthesized enzyme be active before translation termination occurs, i.e., when it is still on the ribosome. In contrast, luciferase molecule without the extension emits light only after its release. Comparing the translation dynamics of these two reporters allows visualization of a delay corresponding to the translation termination event. We demonstrated applicability of this approach for investigating the effects of cis- and trans-acting components, including small molecule inhibitors and read-through inducing sequences, on the translation termination rate. With CTELS, we systematically assessed negative effects of decreased 3′ UTR length, specifically on termination. We also showed that blasticidin S implements its inhibitory effect on eukaryotic translation system, mostly by affecting elongation, and that an excess of eRF1 termination factor (both the wild-type and a non-catalytic AGQ mutant) can interfere with elongation. Analysis of read-through mechanics with CTELS revealed a transient stalling event at a “leaky” stop codon context, which likely defines the basis of nonsense suppression.

CTELS: A Cell-Free System for the Analysis of Translation Termination Rate.

When selenocysteine (Sec) tRNA[Ser]Sec was originally discovered, it was proposed to be the first nonsense suppressor tRNA found in mammalian and avian tissues, since it exclusively decoded the nonsense codon, UGA, which normally dictates the cessation of protein synthesis. This tRNA was subsequently shown to be Sec tRNA, which inserted Sec into protein as the 21st proteinogenic amino acid. Once it was established that this tRNA was aminoacylated with serine by seryl-tRNA synthetase and served as the scaffold for Sec synthesis, Sec tRNA was appropriately named Sec tRNA[Ser]Sec. The mammalian Sec-tRNA[Ser]Sec population consists of two isoforms that differ from each other by a single 2′-O-methyl moiety on the uridine at position 34, designated Um34. The non-Um34 isoform is involved in the synthesis of a subclass of selenoproteins, called housekeeping selenoproteins, while the Um34 isoform supports synthesis of stress-related selenoproteins. These novel functions and other unique features of Sec tRNA are the subjects of this chapter, supporting the idea that this tRNA is the quintessential constituent in selenoprotein biosynthesis.

Selenocysteine tRNA [Ser]Sec : From Nonsense Suppressor tRNA to the Quintessential Constituent in Selenoprotein Biosynthesis

/pdf/chapter-25-selenium-in-biology-and-human-health-40ea7fu0dj.pdf

Chapter 25. Selenium in biology and human health: Controversies and perspectives

Identification of pathways of drug metabolism provides critical information regarding efficacy and safety of these compounds. Particularly challenging cases involve stereospecific processes. We found that broad classes of compounds containing methylsulfinyl groups are reduced to methylsulfides specifically by methionine sulfoxide reductase A, which acts on the S-stereomers of methionine sulfoxides, whereas the R-stereomers of these compounds could not be efficiently reduced by any methionine sulfoxide reductase in mammals. The findings of efficient reduction of S-methylsulfinyls and deficiency in the reduction of R-methylsulfinyls by methionine sulfoxide reductases suggest strategies for improved efficacy and decreased toxicity of drugs and natural compounds containing methylsulfinyls through targeted use of their enantiomers.

/pdf/selective-reduction-of-methylsulfinyl-containing-compounds-3qn8o7wo08.pdf

Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy.

DNA methylation of a defined set of CpG dinucleotides emerged as a critical and precise biomarker of the aging process. Multi-variate machine learning models, known as epigenetic clocks, can exploit quantitative changes in the methylome to predict the age of bulk tissue with remarkable accuracy. However, intrinsic sparsity and digitized methylation in individual cells have so far precluded the assessment of aging in single cell data. Here, we present scAge, a probabilistic approach to determine the epigenetic age of single cells, and validate our results in mice. scAge tissue-specific and multi-cell type single cell clocks correctly recapitulate chronological age of the original tissue, while uncovering the inherent heterogeneity that exists at the single-cell level. The data suggest that while tissues age in a coordinated fashion, some cells age more or less rapidly than others. We show that individual embryonic stem cells exhibit an age close to zero, that certain stem cells in a tissue show a reduced age compared to their chronological age, and that early embryogenesis is associated with the reduction of epigenetic age of individual cells, the latter supporting a natural rejuvenation event during gastrulation. scAge is both robust against the low coverage that is characteristic of single cell sequencing techniques and is flexible for studying any cell type and vertebrate organism of interest. This study demonstrates for the first time the potential for accurate epigenetic age profiling at single-cell resolution.

/pdf/profiling-epigenetic-age-in-single-cells-qw0lebrkrf.pdf

Vadim N. Gladyshev

Papers

CTELS: A Cell-Free System for the Analysis of Translation Termination Rate.

Selenocysteine tRNA [Ser]Sec : From Nonsense Suppressor tRNA to the Quintessential Constituent in Selenoprotein Biosynthesis

Chapter 25. Selenium in biology and human health: Controversies and perspectives

Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy.

Profiling epigenetic age in single cells