A motif in the alphabeta T-cell receptor controls positive selection by modulating ERK activity

Positive selection allows thymocytes that recognize an individual's own major histocompatibility complex (self-MHC) molecules to survive and differentiate, whereas negative selection removes overtly self-reactive thymocytes. Although both forms of thymic selection are mediated by the alphabeta T-cell receptor (TCR) and require self-MHC recognition, an important question is whether they are controlled by distinct signalling cascades. We have shown that mutation of an essential motif within the TCR alpha-chain-connecting peptide domain (alpha-CPM) profoundly affects positive but not negative selection. Using transgenic mice expressing a mutant alpha-CPM TCR we examined the contribution of several mitogen-activated protein kinase (MAPK) cascades to thymic selection. Here we show that in thymocytes expressing a mutant alpha-CPM receptor, a positively selecting peptide failed to activate the extracellular signal-regulated kinase (ERK), although other MAPK cascades were induced normally. The defect in ERK activation was associated with impaired recruitment of the activated tyrosine kinases Lck and ZAP-70, phosphorylated forms of the TCR component CD3zeta and the adaptor protein LAT to detergent-insoluble glycolipid-enriched microdomains (DIGs). Therefore, an intact DIG-associated signalosome is essential for sustained ERK activation, which leads to positive selection.     

Identification of a new class of steroid hormone receptors

The gonads and adrenal glands produce steroids classified into five major groups which include the oestrogens, progestins, androgens, glucocorticoids and mineralocorticoids. Gonadal steroids control the differentiation and growth of the reproductive system, induce and maintain sexual characteristics and modulate reproductive behaviour. Adrenal steroids also influence differentiation as well as being metabolic regulators. The effects of each steroid depend primarily on its specific receptors, the nature of which could therefore provide a basis for classification of steroid hormone action. The successful cloning, sequencing and expression of the human glucocorticoid (hGR) (ref. 1), oestrogen (hER), progesterone (hPR), and mineralocorticoid (hMR) receptors, complementary DNA, plus homologues from various species, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis show structural features common to all groups of steroid hormone receptors. The receptors share a highly conserved cysteine-rich region which functions as the DNA-binding domain. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe. In this study, using the DNA-binding domain of the human oestrogen receptor cDNA as a hybridization probe, we have isolated two cDNA clones encoding polypeptides with structural features suggestive of cryptic steroid hormone receptors which could participate in a new hormone response system.     

A human retinoic acid receptor which belongs to the family of nuclear receptors

A cDNA encoding a protein that binds retinoic acid with high affinity has been cloned. The protein is homologous to the receptors for steroid hormones, thyroid hormones and vitamin D3, and appears to be a retinoic acid-inducible trans-acting enhancer factor, suggesting that the molecular mechanisms of the effect of retinoids (vitamin A) on embryonic development, differentiation and tumour cell growth are similar to those described for other members of this nuclear receptor family.     

微分反馈控制与延迟微分反馈控制

证明了微分反馈控制洛伦兹系统在三个平衡点S0,S1和S2的可控性,提出了延迟微分反馈控制DDFC,DDFC利用可测变量的微商进行反馈,理论证明DDFC加于洛伦兹系统的第3个方程时3个平衡点均不稳定可控,而加于洛伦兹系统的第2个方程时平衡点S0不可控而平衡点Sl和S2稳定可控,用Matlab进行数值仿真,调节延迟时间τ和控制增益k,DDFC系统能自动寻找和稳定不同的不稳定周期轨道UPO,实现混沌控制。     

The limits of the nuclear landscape

In 2011, 100 new nuclides were discovered. They joined the approximately 3,000 stable and radioactive nuclides that either occur naturally on Earth or are synthesized in the laboratory. Every atomic nucleus, characterized by a specific number of protons and neutrons, occupies a spot on the chart of nuclides, which is bounded by 'drip lines' indicating the values of neutron and proton number at which nuclear binding ends. The placement of the neutron drip line for the heavier elements is based on theoretical predictions using extreme extrapolations, and so is uncertain. However, it is not known how uncertain it is or how many protons and neutrons can be bound in a nucleus. Here we estimate these limits of the nuclear 'landscape' and provide statistical and systematic uncertainties for our predictions. We use nuclear density functional theory, several Skyrme interactions and high-performance computing, and find that the number of bound nuclides with between 2 and 120 protons is around 7,000. We find that extrapolations for drip-line positions and selected nuclear properties, including neutron separation energies relevant to astrophysical processes, are very consistent between the models used.     

大学生就业网上行——网络招聘刍议

IT产业的飞速发展给我们的经济、管理生活带来了前所未有的变化。在此背景下,网络招聘以它独特的优势受到了越来越多的人的欢迎。网络招聘具有覆盖面广、信息量大且更新快、招聘网络平台功能强大、效率高、可以更好地维护招聘的公正性以及成本低等优势,同时又存在招聘信息“水分”较多、缺少互动、信息反馈少、竞争更加激烈等劣势。对此,大学生在进行网络招聘时应采取相应的对策。     

原子核衰变与原子核反应的统一

提出把原子核的衰变视为一种特殊的核反应，则衰变能就是这种特殊的核反应过程的反应能．而原子核衰变中的出射粒子动能与衰变能之间的定量关系，就是这种特殊的核反应过程的Q方程；并提出了原子核衰变与原子核反应两部分内容的教学建议．