Cellular and genetic mechanisms of self tolerance and autoimmunity

The mammalian immune system has an extraordinary potential for making receptors that sense and neutralize any chemical entity entering the body. Inevitably, some of these receptors recognize components of our own body, and so cellular mechanisms have evolved to control the activity of these 'forbidden' receptors and achieve immunological self tolerance. Many of the genes and proteins involved are conserved between humans and other mammals. This provides the bridge between clinical studies and mechanisms defined in experimental animals to understand how sets of gene products coordinate self-tolerance mechanisms and how defects in these controls lead to autoimmune disease.     

Changes in carbon dioxide during an oceanic anoxic event linked to intrusion into Gondwana coals

The marine sedimentary record exhibits evidence for episodes of enhanced organic carbon burial known as 'oceanic anoxic events' (OAEs). They are characterized by carbon-isotope excursions in marine and terrestrial reservoirs and mass extinction of marine faunas. Causal mechanisms for the enhancement of organic carbon burial during OAEs are still debated, but it is thought that such events should draw down significant quantities of atmospheric carbon dioxide. In the case of the Toarcian OAE (approximately 183 million years ago), a short-lived negative carbon-isotope excursion in oceanic and terrestrial reservoirs has been interpreted to indicate raised atmospheric carbon dioxide caused by oxidation of methane catastrophically released from either marine gas hydrates or magma-intruded organic-rich rocks. Here we test these two leading hypotheses for a negative carbon isotopic excursion marking the initiation of the Toarcian OAE using a high-resolution atmospheric carbon dioxide record obtained from fossil leaf stomatal frequency. We find that coincident with the negative carbon-isotope excursion carbon dioxide is first drawn down by 350 +/- 100 p.p.m.v. and then abruptly elevated by 1,200 +/- 400 p.p.m.v, and infer a global cooling and greenhouse warming of 2.5 +/- 0.1 degrees C and 6.5 +/- 1 degrees C, respectively. The pattern and magnitude of carbon dioxide change are difficult to reconcile with catastrophic input of isotopically light methane from hydrates as the cause of the negative isotopic signal. Our carbon dioxide record better supports a magma-intrusion hypothesis, and suggests that injection of isotopically light carbon from the release of thermogenic methane occurred owing to the intrusion of Gondwana coals by Toarcian-aged Karoo-Ferrar dolerites.     

基于因特网的智能信息处理系统

本书为《创新智力》丛书的第3卷。因特网使以前不可能实现的难事成为可能，如容易地存取大量信息。但信息量和变量两者以质量形式对介质有效利用产生妨碍。由于这个原因，人工智能将成为有用的工具。智能系统可以用来检索因特网和数据挖掘；解释因特网导出资料、人-Web接口、消除监视条件和诸多新发现。本书提出关于诸如神经网络、自适应和连接者范型、模糊和基于规则的系统、智能代理人等智能系统和因特网之间交互的最新研究，它还纵览帮助和提高使用因特网的智能系统服务及一个通体用智能技术的信道，即因特网的应用。     

Human CtIP promotes DNA end resection

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.     

Lanthanide contraction and magnetism in the heavy rare earth elements

The heavy rare earth elements crystallize into hexagonally close packed (h.c.p.) structures and share a common outer electronic configuration, differing only in the number of 4f electrons they have. These chemically inert 4f electrons set up localized magnetic moments, which are coupled via an indirect exchange interaction involving the conduction electrons. This leads to the formation of a wide variety of magnetic structures, the periodicities of which are often incommensurate with the underlying crystal lattice. Such incommensurate ordering is associated with a 'webbed' topology of the momentum space surface separating the occupied and unoccupied electron states (the Fermi surface). The shape of this surface-and hence the magnetic structure-for the heavy rare earth elements is known to depend on the ratio of the interplanar spacing c and the interatomic, intraplanar spacing a of the h.c.p. lattice. A theoretical understanding of this problem is, however, far from complete. Here, using gadolinium as a prototype for all the heavy rare earth elements, we generate a unified magnetic phase diagram, which unequivocally links the magnetic structures of the heavy rare earths to their lattice parameters. In addition to verifying the importance of the c/a ratio, we find that the atomic unit cell volume plays a separate, distinct role in determining the magnetic properties: we show that the trend from ferromagnetism to incommensurate ordering as atomic number increases is connected to the concomitant decrease in unit cell volume. This volume decrease occurs because of the so-called lanthanide contraction, where the addition of electrons to the poorly shielding 4f orbitals leads to an increase in effective nuclear charge and, correspondingly, a decrease in ionic radii.     

Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin

Semaphorins are axon guidance factors that assist growing axons in finding appropriate targets and forming synapses. Emerging evidence suggests that semaphorins are involved not only in embryonic development but also in immune responses. Semaphorin 7A (Sema7A; also known as CD108), which is a glycosylphosphatidylinositol-anchored semaphorin, promotes axon outgrowth through beta1-integrin receptors and contributes to the formation of the lateral olfactory tract. Although Sema7A has been shown to stimulate human monocytes, its function as a negative regulator of T-cell responses has also been reported. Thus, the precise function of Sema7A in the immune system remains unclear. Here we show that Sema7A, which is expressed on activated T cells, stimulates cytokine production in monocytes and macrophages through alpha1beta1 integrin (also known as very late antigen-1) as a component of the immunological synapse, and is critical for the effector phase of the inflammatory immune response. Sema7A-deficient (Sema7a-/-) mice are defective in cell-mediated immune responses such as contact hypersensitivity and experimental autoimmune encephalomyelitis. Although antigen-specific and cytokine-producing effector T cells can develop and migrate into antigen-challenged sites in Sema7a-/- mice, Sema7a-/- T cells fail to induce contact hypersensitivity even when directly injected into the antigen-challenged sites. Thus, the interaction between Sema7A and alpha1beta1 integrin is crucial at the site of inflammation. These findings not only identify a function of Sema7A as an effector molecule in T-cell-mediated inflammation, but also reveal a mechanism of integrin-mediated immune regulation.     

The early Holocene optimum inferred from a high-resolution pollen record of Huguangyan Maar Lake in southern China

A high-resolution pollen record of the past 13000 a from Huguangyan Maar Lake reveals the vegetation and environment changes in southern China during the Holocene. It shows that (i) pollen percentage of trees and shrubs reached 56% during the early Holocene (11600―7800 cal a BP), of which the pollen percentage of tropical trees reached a maximum at 9500―8000 cal a BP, reflecting a hot and wet envi- ronment; (ii) during the mid-Holocene (7800―4200 cal a BP), the pollen percentage of montane conif- erous trees and herbs increased, while the percentage of tropical-subtropical trees decreased, indi- cating lower temperature and humidity; (iii) in the late Holocene spanning from 4200 to 350 cal a BP, the pollen percentage of herbs and montane conifer increased significantly, indicating a marked decrease of temperature and humidity. Our pollen data reveal that the time period 9500―8000 cal a BP in south- ern China represents a climatic optimum for the Holocene characterized by hot and wet conditions. This is consistent with the Holocene optimum found in lower latitude regions globally. We speculate that strong insolation might cause the northward migration of the ITCZ and subtropical summer mon- soon front, which resulted in an early Holocene optimum in the Huguangyan area. The dry tendency and climate fluctuations of the middle and late Holocene could be associated with a decrease in solar insolation and frequent ENSO event.     

Surface transfer doping of diamond

The electronic properties of many materials can be controlled by introducing appropriate impurities into the bulk crystal lattice in a process known as doping. In this way, diamond (a well-known insulator) can be transformed into a semiconductor, and recent progress in thin-film diamond synthesis has sparked interest in the potential applications of semiconducting diamond. However, the high dopant activation energies (in excess of 0.36 eV) and the limitation of donor incorporation to (111) growth facets only have hampered the development of diamond-based devices. Here we report a doping mechanism for diamond, using a method that does not require the introduction of foreign atoms into the diamond lattice. Instead, C60 molecules are evaporated onto the hydrogen-terminated diamond surface, where they induce a subsurface hole accumulation and a significant rise in two-dimensional conductivity. Our observations bear a resemblance to the so-called surface conductivity of diamond seen when hydrogenated diamond surfaces are exposed to air, and support an electrochemical model in which the reduction of hydrated protons in an aqueous surface layer gives rise to a hole accumulation layer. We expect that transfer doping by C60 will open a broad vista of possible semiconductor applications for diamond.