Insights into T cell development and signal transduction provided by TCR-zeta chain deficient mice

The T cell antigen receptor (TCR) transduces signals that mediate different responses depending on the stage of development of the T cell and the nature of the ligand it engages. The presence of multiple signal transducing subunits (CD3-gamma-delta,-epsilon and zeta chain) suggests the potential to control these responses by altering the subunit composition of the TCR. zeta chain represents an especially important signalling molecule as it contains multiple signalling motifs within its cytoplasmic tail. The generation and analysis of zeta deficient (zeta-/-) and zeta-transgenic mice has provided insight into the role of zeta as well as the CD3 subunits in TCR surface expression, T cell activation and thymocyte development. Herein, we discuss the results from such experiments which suggest distinct roles for zeta chain and the CD3 components at different stages of T cell development.     

The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II

The lantibiotic mersacidin exerts its bactericidal action by inhibition of peptidoglycan biosynthesis. It interferes with the membrane-associated transglycosylation reaction; during this step the ultimate monomeric peptidoglycan precursor, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAc (lipid II) is converted into polymeric nascent peptidoglycan. In the present study we demonstrate that the molecular basis of this inhibition is the interaction of mersacidin with lipid II. The adsorption of [14C]mersacidin to growing cells, as well as to isolated membranes capable of in vitro peptidoglycan synthesis, was strictly dependent on the availability of lipid II, and antibiotic inhibitors of lipid II formation strongly interfered with this binding. Direct evidence for the interaction was provided by studies with isolated lipid II. [14C]mersacidin associated tightly with [14C]lipid II micelles; the complex was stable even in the presence of 1% sodium dodecyl sulfate. Furthermore, the addition of isolated lipid II to the culture broth efficiently antagonized the bactericidal activity of mersacidin. In contrast to the glycopeptide antibiotics, complex formation does not involve the C-terminal D-alanyl-D-alanine moiety of the lipid intermediate. Thus, the interaction of mersacidin with lipid II apparently occurs via a binding site which is not targeted by any antibiotic currently in use.     

Study of susceptibility-induced artefacts in GRASE with different echo train length

The aim of this study was to evaluate the sensitivity of gradient-and-spin-echo (GRASE) sequences to susceptibility effects. GRASE sequences with 21 and 33 echoes per echo train were compared with a T2-weighted FSE sequence with an echo train length of 5 by means of MRI in phantoms, volunteers (n = 10), and patients (n = 19) with old hemorrhagic brain lesions. All experiments were performed on a 1.0-T clinical MR system (Impact Expert, Siemens AG, Erlangen, Germany) with constant imaging parameters. Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations, of brain areas with physiological iron deposition (red nucleus, substantia nigra), and of areas of old brain hemorrhage were calculated for FSE and GRASE pulse sequences. Areas of old brain hemorrhage were also qualitatively analyzed for the degree of visible susceptibility effects by blinded reading. The CNR of iron oxide tubes and iron-containing brain areas decreased with increasing echo trains of GRASE sequences. The CNR of GRASE sequences decreased when compared with CNR of their FSE counterparts (GRASE 21 echo trains 23.8 +/- 0.8, FSE 5 echo trains 26.7 +/- 0.9; p 相似文献