Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance

Recognition of self-antigen-derived epitopes presented by major histocompatibility complex class II (MHC II) molecules on thymic epithelial cells (TECs) is critical for the generation of a functional and self-tolerant CD4 T-cell repertoire. Whereas haematopoietic antigen-presenting cells generate MHC-II-peptide complexes predominantly through the processing of endocytosed polypeptides, it remains unknown if and how TECs use unconventional pathways of antigen presentation. Here we address the role of macroautophagy, a process that has recently been shown to allow for endogenous MHC II loading, in T-cell repertoire selection in the mouse thymus. In contrast to most other tissues, TECs had a high constitutive level of autophagy. Genetic interference with autophagy specifically in TECs led to altered selection of certain MHC-II-restricted T-cell specificities and resulted in severe colitis and multi-organ inflammation. Our findings indicate that autophagy focuses the MHC-II-peptide repertoire of TECs on their intracellular milieu, which notably comprises a wide array of otherwise strictly 'tissue-specific' self antigens. In doing so, it contributes to T-cell selection and is essential for the generation of a self-tolerant T-cell repertoire.     

Peptidergic transmitters in synaptic boutons of sympathetic ganglia

In sympathetic ganglia of the bullfrog, a slow synaptic potential lasting for minutes--the late slow excitatory postsynaptic potential (e.p.s.p.)--was discovered. This slow response, unlike other previously known synaptic potentials in the autonomic nervous system, is not mediated by acetylcholine or monoamines. Similar non-cholinergic, non-adrenergic slow synaptic potentials have since been found in several other vertebrate autonomic ganglia. We found that the late slow e.p.s.p. is probably mediated by a peptide that is identical to, or closely resembles, mammalian luteinizing hormone releasing hormone (LHRH), because (1) when applied directly to sympathetic neurones, LHRH and its agonists elicit a slow depolarization, associated with similar changes in membrane conductance and excitability as those occurring during the late slow e.p.s.p. Furthermore, both peptide-induced and nerve-evoked responses are blocked by antagonists of LHRH; and (2) radioimmunoassays indicate that a chain of sympathetic ganglia contains 100-800 pg of a LHRH-like peptide. Its distribution among spinal nerves, the great reduction of this substance following denervation, and its release from ganglia following isotonic KCl treatment or nerve stimulation suggest that the LHRH-like material is contained in preganglionic nerve fibres. Here we report that immunohistochemical staining of sympathetic ganglia shows that LHRH-like immunoreactivity is indeed present in synaptic boutons. We also show that the two types of ganglion cells (B cells and C cells) receive strikingly different patterns of peptidergic innervation.     

一种改进的启发式属性约简算法

文章对现有启发式属性约简算法进行分析,通过实例说明一般启发式算法求得的相对约简有冗余属性存在的问题.针对这一不足,在算法中加入消除冗余属性的二次约简过程,得到一种改进的启发式属性约简算法.提供了实例分析,验证了该改进算法具有较好的约简效果.     

运筹学线性规划模型求解的计算机应用

结合一特定的线性规划数学模型,在转换为计算机能够识别的格式的基础上,用Excel的solver得出其结果报告及灵敏度分析报告,并简单地对其进行分析,从而为解决线性规划模型手工操作精度低、周期长的问题提供了一条有效途径。     

基于从头算量化参数的BPx网络模型在吡啶类化合物pKa中的应用

用量子化学从头算RHF方法在6-31G水平下对吡啶类分子进行构型全优化,并用优化得到的量化参数作为反向传播人工神经网络的输入向量,并将此模型（人工神经网络）应用到吡啶类化合物pKa值的预测。将预测结果与多元线性回归算法的结果相比较。研究表明,所构造的人工神经网模型在预测吡啶类化合物的pKa值中得到满意的结果．     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

用基因芯片技术分析干旱胁迫下生殖生长期大麦的基因表达

耐旱性是干旱地区稳定和增加大麦产量的一个关键因素。鉴定出与耐旱性相关的功能基因,一方面可了解大麦的耐旱机理,同时还可以促进利用生物技术来改良大麦的耐旱性。在研究中,2个在耐旱性上具有明显差异的大麦品种Tadmor(耐旱)和WI2291(干旱敏感)被选作材料,采用22000个ESTs(基因表达序列标签)的Affymetrix大麦基因芯片Barley1来分析生殖生长期干旱胁迫下2个大麦材料的差异表达基因。研究结果表明,干旱胁迫下2个大麦材料中有77个共调节基因,其中部分基因已被报道过可能与抗旱性相关。这些基因中已有功能注释的基因按其生物学功能被分为14组,猜测它们是干旱胁迫的响应基因,在抗旱性上可能不起重要作用,或者是必需的但单独不足以提高大麦的抗旱性。进一步比较2个材料差异表达的基因,发现二材料之间有372个受干旱调节基因的差异。这些基因中有功能注释基因的生物学功能中可分为15组,其中一些已被认为与抗旱性相关;而对那些未知功能的基因,推测可能亦在大麦的抗旱性上扮演一定的角色。研究所得结果可为阐述生殖生长期大麦的耐旱性机理提供新的认识。     

Fenton氧化工艺处理石油树脂生产废水研究

试验研究了难生物降解石油树脂生产废水Fenton氧化处理效果,考查了各影响因子最佳工艺条件.结果表明,在pH值为2.5、FeSO4投加量为800 mg·L-1、H2O2投加量为3000 mg·L-1、反应时间为2 h、反应温度为50～55℃的条件下,Fenton氧化工艺COD去除率为73%左右.将Fenton氧化处理水同低浓度含油废水混合后经进一步混凝沉淀处理,处理水COD值可降低至350 mg·L-1左右,达到了污水三级排放标准(COD<500 mg·L-1).     

咪唑类离子液体的亲疏水性对电润湿器件性能的影响

文中研究离子液体应用于电润湿显示器件的导电流体性能. 选取极性较大的乙基咪唑为离子液体的阳离子,改变阴离子的亲疏水性,对比了几种离子液体的温度窗口、粘度等物理性质,并重点研究了离子液体亲疏水性对电润湿特性、油墨萃取、器件响应等方面的影响. 同时,在1-乙基-3-甲基咪唑四氟硼酸盐离子液体的阳离子上添加羟基基团,得到具有更强亲水性的离子液体. 结果表明：亲水性高的离子液体在介电材料含氟聚合物表面的初始接触角比较大,对油墨中染料的萃取程度比疏水性离子液体弱,证明了电润湿器件更适合选取亲水性高的离子液体作为导电流体. 最后,以1-乙基-3-甲基咪唑二腈胺盐离子液体作为导电流体制备的电润湿器件得到了较佳的电学和光学响应性能.     

Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins

The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8–12, while the bulk of the plasma proteins was present in fractions 11–28. Vesicle markers peaked in fractions 7–11; however, the same fractions also contained lipoprotein particles. The purity of EVs was improved by combining a density cushion with SEC to further separate lipoprotein particles from the vesicles, which reduced the contamination of lipoprotein particles by 100-fold. Using this novel isolation procedure, a total of 1187 proteins were identified in plasma EVs by mass spectrometry, of which several proteins are known as EV-associated proteins but have hitherto not been identified in the previous proteomic studies of plasma EVs. This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery.