Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells

Natural killer (NK) cells are a subset of lymphocytes that mediate major histocompatibility complex (MHC)-nonrestricted cytotoxicity against tumours and virus-infected cells and secrete numerous cytokines on activation. NK cells are distinct from mature T lymphocytes, because they do not rearrange or productively transcribe T-cell receptor alpha-, beta-, gamma- or delta-chain genes and do not express the CD3 gamma- or delta-subunits. But recent studies indicate that NK cells do express CD3 zeta, co-associated with other membrane proteins. Here we report that CD16, the receptor for the Fc (constant) region of IgG, specifically associates with the CD3 zeta homodimer on the membrane of human NK cells, and that co-transfection with CD3 zeta complementary DNA permits expression of a transmembrane-linked CD16 complex on COS-7 cells. These findings indicate that CD3 zeta can co-associate with membrane receptors of diverse cell types and function as a common structure for signal transduction.     

Platelet secretory products inhibit lipoprotein metabolism in macrophages

Macrophages possess a receptor that binds low-density lipoproteins (LDL) containing lysine residues modified by acetylation (Ac LDL), acetoacetylation (AcAc LDL) or malondialdehyde treatment. This receptor (referred to as the Ac LDL receptor or scavenger receptor) internalizes the bound lipoprotein. As a consequence, massive amounts of cholesteryl esters accumulate so that macrophages in culture resemble foam cells found in atherosclerotic lesions. In an effort to identify an unmodified mammalian macromolecule that binds to the Ac LDL receptor, we investigated whether platelet secretory products affect the receptor-mediated endocytosis of chemically modified lipoproteins. Platelets are a potential source of such activity because they exist in close association with foam cells in developing atherosclerotic lesions. Our study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophages and the subsequent accumulation of cholesteryl esters. This is the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages.     

The CO bond angle of carboxymyoglobin determined by angular-resolved XANES spectroscopy

Our knowledge of the structure of condensed matter has been based primarily on spectroscopic methods that measure first-order pair correlations of atomic arrangements and thus provide interatomic distances (for example neutron and X-ray scattering). Bond angles are given by higher-order correlation functions, and such information can be provided by X-ray absorption near-edge structure (XANES) spectroscopy, the features of which are determined by multiple scattering of photoelectrons whose paths begin and end at the selected absorbing atom. We report here angular-resolved XANES spectroscopy of a single crystal of carboxymyoglobin (MbCO). The large dichroism of the X-ray absorption of the crystal can be fully interpreted by multiple-scattering theory which allows the determination of Fe-ligand bond angles. The analysis of the identified multiple scattering features due to CO in high signal-to-noise-ratio spectra of protein in solution has allowed the determination of the variation of CO bond angles. This opens the way to the determination of subtle structural features due to bond angle variations in proteins in solution which are relevant to an understanding of the characteristics of proteins at the atomic scale.     

Antiquity of clonal salamander lineages revealed by mitochondrial DNA.

The existence of clonally reproducing vertebrates has often served as a foil in attempts to explain the near-ubiquity of sexual reproduction in eukaryotes, but the absence of recombination, with its attendant limitation of new genotypes to those produced through mutations, restricts the adaptive ability of clonal organisms. It has been argued, therefore, that clonal vertebrate taxa have short lifespans. Variation in mitochondrial DNA (mtDNA) within clonal populations is interpreted instead as reflecting multiple, although limited, independent hybridization events. On the basis of an analysis of an average of 373 nucleotide pairs, we report here that the mtDNA of clonal, hybrid, gynogenetic mole salamanders (Ambystoma, Ambystomatidae) differs by 5% or more from mtDNA of their closest possible sexual relatives (A. jeffersonianum, A. laterale and A. texanum). Assuming usual rates of mtDNA divergence, these lineages have persisted for about 5 million years, far longer than estimated for other clonal vertebrate populations. The low mtDNA variability in the clonal lineages suggests that they have undergone population reductions during the Pleistocene.     

Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots

Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots.     

欧美国家博士毕业生就业市场概览

少于一半的博士毕业生朝着职业学术研究的方向发展，随着工商业中的机会的增长，他们所学的一系列有用的技能正日益被用于别处，今天的博士毕业生只有少数能真正指望在大学研究工作中长期任职，这已被包括美国国家科学院（NAS）和国家科学基金会（NSF）的研究组织以及英国政府证实。在美国，仅三分之一得到博士学位的人能指望进入学术研究体系。尽管由于其它领域的需求足够有力，从而使博士的总的失业率相对较低。而学生们正相应地调整他们的期望，考虑学术研究领域以外的职业道路。美国科学工程和政府策略委员会（COSEPUP）报告说，…     

Extinction risk from climate change

Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.