The changing of the guard: Molecular diversity and rapid evolution of β-defensins

Summary Defensins are small cationic peptides involved in innate immunity and are components of the first line of defence against invading pathogens. β-defensins are a subgroup of the defensin family that display a particular cysteine spacing and pattern of intramolecular bonding. These molecules are produced mostly by epithelia lining exposed surfaces and appear to have both antimicrobial and cell signalling functions. The unusually high degree of sequence variation in the mature peptide produced by the paralogous and in some cases orthologous genes implies extensive specialisation and species specific adaptation. Here we review recent functional data that are an important addition to our knowledge of the innate immune response and novel antibiotic design. We also consider the organisation and evolution of the genomic loci harbouring these genes where radical and rapid changes in β-defensin sequences have been shown to result from the interplay of both positive and negative selection. Consequently these genes provide some unusually clear glimpses of the processes of duplication and specialisation that have shaped the mammalian genome.     

Development of Fish Immunity and the Role of β-Glucan in Immune Responses

Administration of β-glucans through various routes, including immersion, dietary inclusion, or injection, have been found to stimulate various facets of immune responses, such as resistance to infections and resistance to environmental stress. β-Glucans used as an immunomodulatory food supplement have been found beneficial in eliciting immunity in commercial aquaculture. Despite extensive research involving more than 3000 published studies, knowledge of the receptors involved in recognition of β-glucans, their downstream signaling, and overall mechanisms of action is still lacking. The aim of this review is to summarize and discuss what is currently known about of the use of β-glucans in fish.     

Chemistry of Lipid A: At the Heart of Innate Immunity

In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD‐2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.     

pH Responsive Poly(Amino Acid) Nanoparticles as Potent Carrier Adjuvants for Enhancing Cellular Immunity

Adjuvants are widely used in vaccine to improve the protection or treatment efficacy. However, so far they inevitably produce side effects and are hard to induce cellular immunity in practical application. Herein, two kinds of amphiphilic poly(glutamic acid) nanoparticles (α-PGA-F and γ-PGA-F NPs) as nanocarrier adjuvants are fabricated to induce an effective cellular immune response. Amphiphilic PGA are synthesized by grafting phenylalanine ethyl ester to form biodegradable self-assembly nanoadjuvants in a water solution. The model antigen, chicken ovalbumin (OVA), can be loaded into PGA-F NPs (OVA@PGA-F NPs) with the high loading ratio >12%. Moreover, compared with γ-PGA-F NPs, the acidic environment can induce the α-helical secondary structure of α-PGA NPs, promoting membrane fusion and more fast antigen lysosomal escape. Hence, the antigen presenting cells treated with OVA@α-PGA-F NPs show higher secretion of inflammatory cytokines, and higher expression of major biological histocompatibility complex class I and CD80 than those of OVA@γ-PGA-F NPs. Overall, this work indicates that pH responsive α-PGA-F NPs as a carrier adjuvant can effectively improve the ability of cellular immune responses, leading to it being a potent candidate for vaccine applications.     

Potency of Attenuated Eimeria tenella in Protective Immunity Induction on Homologous and Heterologous Challenges

The aim of this study was to know the protective immunity of broilers immunized with attenuated Eimeria tenella (E. tenella) on homologous and heterologous challenges. The protective immunity was represented by oocyst production and histopathological changes of cecum. The previous experiment already produced attenuated E. tenella through serial passages of precocious lines in naive chicken. Four groups of chickens were separately divided into two non-immunized control groups and two immunized with attenuated E. tenella groups, and each group was challenged with homologous and heterologous strains. The results showed significant difference in oocysts production (p<0.01) and histopathological changes between control and immunized groups.     

关联白噪声对抗肿瘤体系免疫效果的影响

在免疫监视的Logistic肿瘤生长动力学模型中引入关联的乘性白噪声,并考虑抗肿瘤体系的免疫系统激活阈值存在差异,对上述动力学生长方程进行数值仿真计算.发现噪声关联强度能够调节抗肿瘤体系个体的免疫效果,但调节的结果存在差异;噪声关联强度λ的取值存在一个最佳区间,在该区间内更多的抗肿瘤体系个体能实现最大免疫效果. 关键词： Logistic生长模型 随机涨落 肿瘤 免疫     

一种新颖的高灵敏度光纤光栅带宽调谐机构

设计了一种由一直梁和两个半圆拱组成的开口环结构,并将均匀光纤布拉格光栅斜贴于直梁中间的表面处。对两半圆拱施加与直梁方向平行的应力作用时,光纤光栅受到线性应力场的作用,光纤布拉格光栅即转化为啁啾光纤光栅。该机构实现了光纤光栅带宽的线性调谐,线性度高达0．9982,实验结果与理论分析一致。与以往的带宽调谐机构相比,该机构具有很高的应力灵敏度,在20N力的作用下,可产生约7nm的带宽反射,灵敏度达0．34nm／N。利用环境温度对带宽调谐无影响的特性,采用带宽编码技术,研制出具有温度自动补偿特性、高灵敏度的带宽调谐装置。     

小儿支气管哮喘与微量元素临床研究

为探讨微量元素与小儿支气管哮喘的发病关系,以及观察用微量元素治疗小儿支气管哮喘的效果,随机选择支气管哮喘患儿病例72例,进行了全血微量元素Zn、Cu、Fe、Ca的检测,同时使用Zn及Ca制剂治疗,观察其疗效。结果表明,小儿支气管哮喘与Zn、Ca缺乏及免疫功能低下有密切关系,补充上述两种元素对提高其免疫功能进而提高本病疗效有重要价值。     

一类带有潜伏期和部分免疫的传染病模型的全局分析

通过假设被接种者具有部分免疫,建立了一类具有潜伏期和接种的SEIR传染病模型,借助再生矩阵得到了确定此接种模型动力学行为的基本再生数.当基本再生数小于1时,模型只有无病平衡点;当基本再生数大于1时,除无病平衡点外,模型还有唯一的地方病平衡点.借助Liapunov函数,证明了无病平衡点和地方病平衡点的全局稳定性.     

Enzymatic kinetic resolution of 1,1-dioxo-2,3-dihydro-1H-1λ-thiophen-3-ol via temporary derivatisation

Following the thio-conjugate addition of (±)-9, its enantiomers were extremely efficiently discriminated using Novozym 435^®. The thio-differentiating unit may then be removed either under reductive conditions, using Raney nickel, or following an oxidation-elimination sequence. In this manner enantioenriched derivatives of 1,1-dioxo-2,3-dihydro-1H-1λ⁶-thiophen-3-ol 9 may be accessed.