A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction

In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline‐rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N‐(2‐hydroxypropyl)methacrylamide polymer backbone. When added to GADS‐containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross‐linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins.     

Induction of a Melanoma‐Specific Antibody Response by a Monovalent,but not a Divalent,Synthetic GM2 Neoglycopeptide

Human tumor cell‐specific antibodies were induced in mice after immunization with a synthetic glycopeptide, which is based on the GM2 ganglioside carbohydrate moiety produced on a gram scale in bacteria. Such neoglycopeptides represent a promising cancer vaccine strategy for active immunotherapy targeting carbohydrates.

     

淋巴细胞的时间语义逻辑模型及其演化策略

数字序列抗原内部存在许多语义特征,针对抗原进行语义识别可以提高系统检测的准确性。基于抗原的相对时序关系,该文采用了一阶逻辑作为抗原和淋巴细胞的基本描述语言,以扩展逻辑程序构造淋巴细胞的时间语义逻辑模型,给出了淋巴细胞的逻辑表示形式。基于逻辑程序的稳定模型语义学,用稳定模型语义计算作为新的淋巴细胞的匹配算法。借鉴遗传归纳逻辑程序GILP的基本思想,给出了新的淋巴细胞的演化算法。     

食物过敏原及检测技术的研究进展

食物过敏是当前食品安全领域较为突出的问题,综述食品过敏原、过敏的免疫学发生机制及检测技术等方面的研究现状及发展展望,涉及致敏的食物种类及相应过敏原,过敏的免疫学分子发生机理,并对食物过敏原现存的检测技术做了相关的介绍。     

免疫学法检测黄曲霉毒素的研究进展

黄曲霉毒素是黄曲霉菌和寄生曲霉菌的次生代谢产物,是世界卫生组织公认的致癌物。目前,对黄曲霉毒素的检测方法有薄层层析法、高效液相色谱法和酶联免疫吸附法等,其中免疫化学方法具有特异性强、灵敏度高和快速简便等优点,在黄曲霉毒素的检测中应用广泛。建立快速、简便和无毒的检测体系将成为今后检测AFT的研究热点。     

食源性致病菌免疫及分子检测新技术研究进展

食源性致病菌是指以食物为载体,导致人类发生疾病的细菌。传统的以培养为基础的检测方法操作复杂、特异性不强、所需时间长,而近年来发展起来的免疫学方法及分子生物学方法广泛应用于食源性致病菌的检测,克服了传统检测方法的不足。目前常用的免疫学方法主要包括ELISA、免疫磁性分离技术和免疫胶体金技术等;分子生物学方法则主要有依赖PCR的DNA指纹图谱技术、多重PCR、基因芯片、定量PCR和实时荧光定量PCR等技术。     

Captopril,a Renin–Angiotensin System Inhibitor,Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy

(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin–angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b⁺Ly6C^Hi p < 0.05, CD11b⁺Ly6C^Lo p < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (T_RM)-like CD8⁺ (p < 0.001) and double-negative (CD4^-CD8^-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1⁺ hepatic T_RMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.     

The immunomodulatory potential of natural compounds in tumor-bearing mice and humans

Abstract

Cancer is considered a fetal disease caused by uncontrolled proliferation and progression of abnormal cells. The most efficient cancer therapies suppress tumor growth, prevent progression and metastasis, and are minimally toxic to normal cells. Natural compounds have shown a variety of chemo-protective effects alone or in combination with standard cancer therapies. Along with better understanding of the dynamic interactions between our immune system and cancer development, nutritional immunology—the use of natural compounds as immunomodulators in cancer patients—has begun to emerge. Cancer cells evolve strategies that target many aspects of the immune system to escape or even edit immune surveillance. Therefore, the immunesuppressive tumor microenvironment is a major obstacle in the development of cancer therapies. Because interaction between the tumor microenvironment and the immune system is a complex topic, this review focuses mainly on human clinical trials and animal studies, and it highlights specific immune cells and their cytokines that have been modulated by natural compounds, including carotenoids, curcumin, resveratrol, EGCG, and β-glucans. These natural compounds have shown promising immune-modulating effects, such as inhibiting myeloid-derived suppressor cells and enhancing natural killer and cytolytic T cells, in tumor-bearing animal models, but their efficacy in cancer patients remains to be determined.     

疫苗算法及其在车辆故障检测中的应用

根据免疫学原理提出了一种适合于故障诊断的算法--疫苗算法.当出现未知抗原时提取系统内记忆的此类抗原特征并对其进行分析，再将此人工抗原输入到系统中刺激系统并产生相应的抗体，当此抗原再次出现时作出免疫应答.论述了抗体和抗原结构的数学模型以及抗体数据的产生机理.运用此算法开发了具有边检测边学习功能的检测系统，能够充分捕捉反映被测车辆状态的信号特征.将此算法应用于汽车驱动桥的故障检测中，准确率达到95％.工程应用表明，此算法在小样本获取、连续学习、数据压缩等方面具有明显的优越性和有效性.     

Occam’s razor gets a new edge: the use of symmetries in model selection

We demonstrate the power of using symmetries for model selection in the context of mechanistic modelling. We analyse two different models called the power law model (PLM) and the immunological model (IM) describing the increase in cancer risk with age, due to mutation accumulation or immunosenescence, respectively. The IM fits several cancer types better than the PLM implying that it would be selected based on minimizing residuals. However, recently a symmetry-based method for model selection has been developed, which has been successfully used in an in silico setting to find the correct model when traditional model fitting has failed. Here, we apply this method in a real-world setting to investigate the mechanisms of carcinogenesis. First, we derive distinct symmetry transformations of the two models and then we select the model which not only fits the original data but is also invariant under transformations by its symmetry. Contrary to the initial conclusion, we conclude that the PLM realistically describes the mechanism underlying the colon cancer dataset. These conclusions agree with experimental knowledge, and this work demonstrates how a model selection criterion based on biological properties can be implemented using symmetries.