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肥胖与癌症;隐形与解剖;免疫与硬化症;ClampFISH与核酸检测;高通量&单细胞&T细胞受体

已有 3835 次阅读 2018-11-13 22:33 |个人分类:百日千篇|系统分类:科研笔记

Plump mice help to unravel the tangled ties between obesity and cancer

immunology 3.4 18Nov. https://www.nature.com/articles/d41586-018-07390-1

【summery】PD-1蛋白在肥胖小鼠中的含量更高,下游作用于荷尔蒙leptin,促进了肿瘤的发生。

  1. PD-1蛋白由免疫T细胞表达,抑制免疫系统的反应。leptin(瘦素)增强食欲appetite。

    Plump mice;thin mice;obese mice;non-obese counterparts

    fuel tumour growth

    render tumours sensitive to

    be more vulnerable to


Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade

Nature Medicine 32.6  18 Nov.  https://www.nature.com/articles/s41591-018-0221-5

跟上一篇文章结论很像。一天online的 NoV.12。没有细看,不知道为什么发到如此悬殊的杂志上。稍微瞄了一眼,有一点,这篇文章有一些人等的数据(across multiple species and tumor models),可能是这个原因。那一篇标题就表明了,只是再mouse里。

【summery】PD-1/PD-L1,肥胖,T cell, Leptin


'Invisible' mice reveal anatomical secrets解剖学的

nature 41.6 news  18Nov.  https://www.nature.com/articles/d41586-018-07336-7    22min

Gif showing a clip of panoptic vDISCO imaging revealing nerves (green) in a mouse

【summery】透明化死亡的啮齿类动物与纳米抗体的结合,原位探究损伤后或正常难以观察到的结构与功能的关系。

  1. vDISCO技术:将死尸透明化以及坚硬化处理

  2. ‘nanobodies’: 纳米抗体,体积仅为一般抗体的1/10,同时具有抗体的与抗原结合的特性,容易通过微小血管。(antibodies that are found only in llamas美洲驼, camels骆驼 and alpacas羊驼, and are one-tenth the size of antibody molecules in other species. Similar to their larger cousins, nanobodies can be engineered to stick to specific proteins that are found only in one type of cell — while carrying fluorescent green markers that labels the chosen cells. And because nanobodies are so small, they can easily pass through tiny blood vessels and into organs.)

anatomical secrets

unprecedented view

pinpoint specific tissues

rigid and see-through;transparent and hard like plastic 

Crystal clear

soaking a mouse's body in organic solvents to strip it of fats and pigments (coloring)

shrinks by up to 60%

nanobodies

fantastic technology

vessels that run between the skull and the brain

lymphatic vessels; ~transports lymph

confirming scientists' suspicions

a mouse's torso

stick to specific proteins


Immune-cell crosstalk in multiple sclerosis多发性硬化症

nature 41.6 news and views 18 oct.  https://www.nature.com/articles/d41586-018-07063-z   17min

【summery】脑疾病多发性硬化症中T细胞与B细胞相互作用。B细胞在大脑中产生了一个蛋白RASGRP2,T细胞识别了这个蛋白。

【大意】B细胞产生蛋白RASGPR2, HLA将其呈递给T细胞受体(TCR),T细胞被激活,T细胞和B细胞都自我增殖。通过未知途径,它们通过了血脑屏障,对于大脑中表达RASGRP2蛋白的细胞产生攻击,炎症因子产生。比如,T细胞激活的IFN-γ蛋白激起巨噬细胞的作用,攻击了包裹保护神经的髓鞘,如此就可以导致多发性硬化症。所以还是属于自体免疫病。

(One factor linked3,4 to the risk of developing multiple sclerosis is the possession of a particular version of a protein called HLA. HLA proteins enable cells to display antigens — fragments of proteins — on their surfaces. If the receptor for an antigen (the T-cell receptor; TCR) on a T cell recognizes an antigen presented by an HLA protein, the T cell is activated to trigger an immune response against cells that express the antigen. Variations in the antigen-binding capacity of different HLA proteins and in the antigen-recognition capacity of TCRs enable the body to respond to a wide range of antigens associated with disease-causing microorganisms. However, there is a danger that if an HLA protein efficiently binds an antigen that is normally part of the body, and if a T cell that recognizes the HLA–antigen complex is activated, autoimmunity could develop. Such a mechanism might underlie the fact that the version of HLA called HLA-DR15 is a risk factor for multiple sclerosis3, and is estimated4 to contribute 60% of the total genetic risk for developing the condition.)

(Figure 1 | Immune-cell action associated with multiple sclerosis. Jelcic et al.2 report that B cells of the immune system present in the bloodstream make a protein called RASGRP2. These cells use a protein called HLA to present a peptide fragment (an antigen) of RASGRP2 on their cell surface. If this antigen is recognized by the T-cell receptor (TCR) of another immune cell called a T cell, this interaction leads to the proliferation of both the T cells and the B cells, a phenomenon that the authors call autoproliferation. Their evidence indicates that these autoproliferating T cells can, by an unknown route, cross the blood–brain barrier to enter the brain. RASGRP2 is also found in brain tissue. If neurons or other brain cells express RASGRP2, this might trigger T cells that infiltrate the brain to orchestrate an autoimmune attack by producing inflammatory mediators. For example, the production of IFN-γ proteins by activated T cells could stimulate the macrophages of the immune system, which are known6,7 to attack the myelin-sheath structure that protects nerve fibres and supports neuronal function. This in turn could lead to the development of multiple sclerosis.)

are implicated in

It emerges that

brain disease multiple sclerosis

are more prone to 


ClampFISH detects individual nucleic acid molecules using click chemistry–based amplification

NBT  35.7  18 Nov.   https://www.nature.com/articles/nbt.4286     15min

image.png

【summery】ClampFISH通过形成类似双螺旋的结构,利用基于化学的放大信号方法,实现高精度与强度检测单个核苷酸。可以用于组织样本中的检测。

  1. fluorescence in situ hybridization (FISH):Methods for detecting single nucleic acids in cell and tissues, are limited by relatively low signal intensity and nonspecific probe binding.

  2. click-amplifying FISH (clampFISH), a method for fluorescence detection of nucleic acids that achieves high specificity and high-gain (>400-fold) signal amplification. 

are ligated together


High-throughput determination of the antigen specificities of T cell receptors in single cells

NBT 35.7 18 NOV.  https://www.nature.com/articles/nbt.4282

image.png

Workflow for generation of DNA-BC pMHC tetramers

我们提出了四聚体相关T细胞受体序列( tetcr - seq ),以高通量将T细胞受体序列与它们在单细胞中的同源抗原连接起来。结合是通过体外转录和翻译快速产生的DNA条形码抗原四聚体文库来确定的。我们应用tetcr - seq来鉴定TCR与癌症新抗原交叉反应的模式,并快速分离与野生型抗原没有交叉反应的新抗原特异性TCR。

哈哈,没看懂,着急实验以及回去休息,要早起,不想看了,要去做实验了/吐舌头。

就是利用T细胞受体的一些序列与抗原序列,扩增,检测序列特性,进行抗原分类吧。


OHTER VOCABULARY GATHERED WHEN READING PAPERS

stochastic choice

indelible marking

adeno-associated viral vectors

jellyfish GFP fluoresces

disproportionate expression

plasma membrane

drawbacks and advantages

microbial   growth

multi-sample   algorithm 

contigs and   coverage values

metagenomic sample

high-speed   multispectral imaging

high-throughput   strategy

Fecal microbiota




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