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The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.  相似文献   

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Millisecond pulsars are thought to be neutron stars that have been spun-up by accretion of matter from a binary companion. Although most are in binary systems, some 30% are solitary, and their origin is therefore mysterious. PSR J1719-1438, a 5.7-millisecond pulsar, was detected in a recent survey with the Parkes 64-meter radio telescope. We show that this pulsar is in a binary system with an orbital period of 2.2 hours. The mass of its companion is near that of Jupiter, but its minimum density of 23 grams per cubic centimeter suggests that it may be an ultralow-mass carbon white dwarf. This system may thus have once been an ultracompact low-mass x-ray binary, where the companion narrowly avoided complete destruction.  相似文献   

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Alpha-synuclein is implicated in several neurodegenerative disorders, such as Parkinson's disease and multiple system atrophy, yet its functions remain obscure. When expressed in yeast, alpha-synuclein associated with the plasma membrane in a highly selective manner, before forming cytoplasmic inclusions through a concentration-dependent, nucleated process. Alpha-synuclein inhibited phospholipase D, induced lipid droplet accumulation, and affected vesicle trafficking. This readily manipulable system provides an opportunity to dissect the molecular pathways underlying normal alpha-synuclein biology and the pathogenic consequences of its misfolding.  相似文献   

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Peptidoglycan glycosyltransferases (GTs) catalyze the polymerization step of cell-wall biosynthesis, are membrane-bound, and are highly conserved across all bacteria. Long considered the "holy grail" of antibiotic research, they represent an essential and easily accessible drug target for antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus. We have determined the 2.8 angstrom structure of a bifunctional cell-wall cross-linking enzyme, including its transpeptidase and GT domains, both unliganded and complexed with the substrate analog moenomycin. The peptidoglycan GTs adopt a fold distinct from those of other GT classes. The structures give insight into critical features of the catalytic mechanism and key interactions required for enzyme inhibition.  相似文献   

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根据差异教育理论及农林院校中物理学科的特点,结合作者在大学物理教学中尝试差异化教学的实践,着重探讨了差异教育在大学物理教学中的必要性和课堂教学模式改革中的应用。  相似文献   

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