Structural basis for self-association and receptor recognition of human TRAF2

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.     

1-(substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi in mice

1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi infections in mice. The most active compounds are the 1-(4-chlorobenzyl)- and 1-(3,4-dichlorobenzyl)-analogs (L-153,094 [2] and L-153,153 [4], resp.) which are approximately 7-fold more potent upon oral administration than nifurtimox (Lampit) in suppressing parasite levels in the blood of mice with acute Trypanosoma cruzi infections.     

认识信息传播规律 拓展高校信息服务领域

对信息传播规律进行了较深入的研究,包括“信息—媒介”的关系以及“信息—媒介—受众”的规律,论述了拓展高校的信息服务领域及服务反馈的问题。     

Z[√-2]中两整数的平方差

给出了Z[√-2]中的非零整数表示为Z[√-2]中的两整数平方差的表示种数，还给出了Z[√-2]中的非零整数表示为x^2＋2y^2（其中x，y∈Z[√-2]）形式的表示种数．     

Structure and electrical characteristics of Nb-doped SrTiO3 substrates

Strontium titanate (SrTiO3) has been widely used as substrates for growing perovskite oxides thin films be- cause SrTiO3 is chemically and compositionally stable, and has small lattice mismatch with many perovskite oxides[1―3]. It is known that SrTiO3 it…     

dNTP pools imbalance as a signal to initiate apoptosis

Fidelity in DNA synthesis and repair is largely dependent on a balanced supply of deoxynucleotide triphosphate (dNTP) pools. Results from different groups have shown that alterations in dNTP supply result in DNA fragmentation and cell death with characteristics of apoptosis. We have recently shown that in apoptosis driven by deprivation of interleukin-3 (IL-3) in a murine hemopoietic cell line, there is a rapid imbalance in the availability of dNTP that precedes DNA fragmentation. In these cells, dNTP pool balance is closely coupled to the function of the salvage pathway of dNTP synthesis. Apoptosis, induced by treatment of these cells with drugs that inhibit the de novo dNTP synthesis, is prevented when dNTP precursors are supplied through the salvage pathway. IL-3 regulates thymidine kinase activity, suggesting that alterations in dNTP metabolism after IL-3 deprivation could be a relevant event in the commitment of hemopoietic cells to apoptosis.     

Heterochromatin characterization and distribution in the chromosomes of two populations ofIdotea baltica basteri Audouin, 1826 (Isopoda,Valvifera)

Two mediterranean populations ofIdotea baltica basteri from Messina and Naples showed a set of chromosomes composed by 58 all-biarmed chromosomes. The heterochromatin was located in the pericentromeric region of the chromosomes, and its composition appeared heterogeneous. In fact, not all the homologs showed heterochromatin resistant to digestion with three restriction enzymes (Alu I, Hae III and Sau 3A). Moreover, the two populations showed polymorphism in a band of G+C-rich telomeric heterochromatin, which was present only in the population from Messina. It is hypothesized that chromosomal polymorphism might reflect the geographical isolation of the two populations. It is also suggested that a process of diversification is taking place.     

Emancipatory practice through the Sky River Project

Timothy Kennedy went to an Eskimo village in Alaska as a VISTA volunteer to perform community service for 2 years. He remained through 11 years, building participatory community development projects. As he became accepted by the Eskimo villagers, he got them involved in using videotape technology to build community solidarity and then to communicate more effectively with government officials and politicians about the needs and wishes of their community. So as to make clear that this was not a documentary project directed by a professional film maker, Kennedy got villagers involved in all stages of the process of videotaping and also in determining who and how their tapes should be seen by authorities. The Sky River Project achieved three major changes in governmental policies for the Eskimos. As the videotapes were shown in other Eskimo villages, who shared the same needs and wishes, the process generated intervillage communication and collaboration on various projects.     

Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules

Cell-cell interactions are of critical importance during neural development, particularly since the migration of neural cells and the establishment of functional interactions between growing axons and their target cells has been suggested to depend upon cell recognition processes. Neurone-neurone adhesion has been well studied in vitro, and is mediated in part by the neural cell adhesion molecule N-CAM. N-CAM-mediated cell-cell adhesion has been postulated to occur by a homophilic binding mechanism, in which N-CAM on the surface of one cell binds to N-CAM on a neighbouring cell. Studies in our laboratory have identified a cell surface glycoprotein, now known to be N-CAM, which participates in cell-substratum interactions in the developing chicken nervous system. Although this adhesion involves a homophilic binding mechanism, the binding of the cell surface proteoglycan heparan sulphate to the glycoprotein is also required. This raises the question of whether the binding of heparan sulphate to N-CAM is also required for cell-cell adhesion. Here we show that the binding of retinal probe cells to retinal cell monolayers is inhibited by heparin, a functional analogue of heparan sulphate, but not by chondroitin sulphate. Monoclonal antibodies that recognize two different domains on N-CAM, the homophilic-binding and heparin-binding domains, inhibit cell-cell adhesion. The heparin-binding domain isolated from N-CAM by selective proteolysis also inhibits cell-cell adhesion when bound to the probe cells.     

Structure of pre-pro-von Willebrand factor and its expression in heterologous cells

Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260-275K. Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure.