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

B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Dendritic cells and the control of immunity

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

/pdf/exosome-mediated-transfer-of-mrnas-and-micrornas-is-a-novel-9o52kfcb0e.pdf

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells

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

The Hallmarks of Aging

688 Identification of human liver myeloid (CD11C+) and lymphoid (CD123+) dendritic cells and their roles in autoimmune liver diseases and liver viral hepatitis

It has been estimated that worldwide 600,000 babies are born annually with significant congenital heart disease (1). Congenital heart and related vascular defects cause increased flow and pulmonary pressure leading to unfavorable vascular remodeling that results in pulmonary arterial hypertension (1). Developing tissue engineered replacements that mimic the growth and remodeling behavior of native tissue is the optimal approach in treatment of congenital arterial anomalies. The understanding of the underlying mechanisms leading to pulmonary arterial hypertension as well as replicating native pulmonary artery functionality in engineered replacements requires knowledge of native tissue mechanics and growth behavior. In the present study, we report novel information on the changes in the structure-mechanics behavior of the growing pulmonary artery.Copyright © 2012 by ASME

Regional Biomechanical and Microstructural Alterations of the Ovine Main Pulmonary Artery During Postnatal Growth

The NLRP3 inflammasome is a caspase-1-containing complex involved in the maturation of pro-inflammatory cytokines IL-1β and IL-18. NLRP3, independent of its inflammasome functions, also plays a role in a cathepsin B-dependent, caspase-1-independent necrotic cell death process known as pyronecrosis. We have previously shown that the cholesterol-dependent, pore-forming toxin tetanolysin O (TLO) triggers IL-1β release from LPS-primed murine bone marrow-derived macrophages (BMDM) in a NLRP3 inflammasome- and cathepsin B-dependent manner. The work contained herein supports an additional role for TLO in the necrosis of LPS-primed BMDM. Both a low and a high TLO dose induce release of lactate dehydrogenase (LDH) and high mobility group box 1 (HMGB1) and this release is NLRP3-dependent for the low toxin dose. Low dose TLO-induced HMGB1 release is also dependent on the activities of caspase-1 and cathepsin B, suggesting a novel form of cell death that is distinct from caspase-1-independent pyronecrosis. We also observe via fixed cell microscopy that TLO causes HMGB1 to move from the nucleus to the cytoplasm in LPS-primed BMDM and that HMGB1 release is dependent on NLRP3 activity. To our knowledge, this is the first study to visualize HMGB1 localization in cells lacking NLRP3. These results provide information on the regulation of HMGB1 release and could eventually lead to new therapeutic approaches to target HMGB1, which contributes to many inflammatory diseases.

NLRP3 inflammasome-dependent HMGB1 release induced by a bacterial pore-forming toxin (136.15)

Development of a Small-Scale Aeroacoustic Open Jet, Open Return Wind Tunnel for Cavity Noise and Component Testing

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link cortical actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies genes with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify genes with evolutionary histories similar to shotgun (shg), which encodes the Drosophila E-cadherin (DE-Cad) ortholog. Core adherens junction components ?-catenin and p120-catenin displayed strong ERC correlations with shg, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the shg ERC profile revealed a collection of genes not previously associated with shg function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidate genes by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-Cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol (“to split” in Russian) and show that it regulates DE-Cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-Cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.

https://www.biorxiv.org/content/biorxiv/early/2018/09/27/429472.full.pdf

Simon C. Watkins

Papers

688 Identification of human liver myeloid (CD11C+) and lymphoid (CD123+) dendritic cells and their roles in autoimmune liver diseases and liver viral hepatitis

Regional Biomechanical and Microstructural Alterations of the Ovine Main Pulmonary Artery During Postnatal Growth

NLRP3 inflammasome-dependent HMGB1 release induced by a bacterial pore-forming toxin (136.15)

Development of a Small-Scale Aeroacoustic Open Jet, Open Return Wind Tunnel for Cavity Noise and Component Testing

Evolutionary rate covariation analysis of E-cadherin identifies Raskol as regulator of cell adhesion and actin dynamics in Drosophila