The SWI1, SWI2, and SWI3 proteins, which are required for regulated transcription of numerous yeast genes, were found also to be essential for rat glucocorticoid receptor function in yeast; the ...receptor failed to activate transcription in strains with mutations in the SWI1, SWI2, or SWI3 genes. Certain mutations in genes encoding components of chromatin, identified as suppressors of swi mutations, partially relieved the SWI$^-$ requirement for receptor function. Immunoprecipitation of glucocorticoid receptor derivatives from wild-type (SWI$^+$) yeast extracts coprecipitated the SWI3 protein; such receptor-SWI3 complexes were not detected in swi1$^-$ or swi2$^-$ mutant strains, implying that a complex of multiple SWI proteins may associate with the receptor. Prior incubation of a Drosophila embryo transcription extract with the yeast SWI3-specific antibody inhibited receptor function in vitro whereas the antibody had no effect if added after initiation complex formation. Thus, positive regulation by the glucocorticoid receptor in vivo and in vitro appears to require its interaction, at an early step, with one or more SWI proteins.
Since compensation for rotation centers is insufficient for accurate 5-axis manufacturing, compensation for kinematic errors of the rotary axis is demanded. Although touch trigger probes are widely ...used, interference with other components often limits their measurement range and accuracy. This article proposes a method to identify kinematic parameters for the entire stroke of the swiveling axis at once from a measured dataset taken at different measurement locations depending on the indexing angle of the swiveling axis. The proposed method is experimentally evaluated on a horizontal 5-axis machining center.
Optimal T cell activation requires the interactions of co-stimulatory molecules, such as those in the CD28 and B7 protein families. Recently, we described the co-stimulatory properties of the murine ...ligand to ICOS, which we designated as B7RP-1. Here, we report the co-stimulation of human T cells through the human B7RP-1 and ICOS interaction. This ligand–receptor pair interacts with a KD ~ 33 nM and an off-rate with a t½ > 10 min. Interestingly, tumor necrosis factor (TNF)-α differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-α enhances B7RP-1 expression on B cells and monocytes, while it inhibits it on DC. The human B7RP-1–Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell proliferation in vitro. Specific cytokines, such as IFN-γ and IL-10, are induced by B7RP-1 co-stimulation. Although IL-2 levels are not significantly increased, B7RP-1 co-stimulation is dependent on IL-2. These experiments define the human ortholog to murine B7RP-1 and characterize its interaction with human ICOS.
NF-kappa B-inducing kinase (NIK) is involved in lymphoid organogenesis in mice through lymphotoxin-beta receptor signaling. To clarify the roles of NIK in T cell activation through TCR/CD3 and ...costimulation pathways, we have studied the function of T cells from aly mice, a strain with mutant NIK. NIK mutant T cells showed impaired proliferation and IL-2 production in response to anti-CD3 stimulation, and these effects were caused by impaired NF-kappa B activity in both mature and immature T cells; the impaired NF-kappa B activity in mature T cells was also associated with the failure of maintenance of activated NF-kappa B. In contrast, responses to costimulatory signals were largely retained in aly mice, suggesting that NIK is not uniquely coupled to the costimulatory pathways. When NIK mutant T cells were stimulated in the presence of a protein kinase C (PKC) inhibitor, proliferative responses were abrogated more severely than in control mice, suggesting that both NIK and PKC control T cell activation in a cooperative manner. We also demonstrated that NIK and PKC are involved in distinct NF-kappa B activation pathways downstream of TCR/CD3. These results suggest critical roles for NIK in setting the threshold for T cell activation, and partly account for the immunodeficiency in aly mice.
We present a study on the
β
decays of the neutron-rich isotopes
37
Al and
38
Al, produced by projectile fragmentation of a
48
Ca beam with an energy
E
= 345
A
MeV at the RIKEN Nishina Center. The ...half-lives of
37
Al and
38
Al have been measured to 11.5(4)ms and 9.0(7)ms, respectively, using the CAITEN implantation and decay detector setup. The level schemes for
37
Si and
38
Si were deduced by employing
γ
-
γ
coincidence spectroscopy following the event-by-event identification of the implanted nuclei. Comparison to large scale nuclear shell model calculations allowed for a tentative assignment of spin and parity of the populated states. The data indicate that the classical shell gap at magic neutron number
N
= 28 between the
νf
7/2
and
νp
3/2
orbits gets reduced by 0.3 MeV in this region leading to low-energy states with intruder configuration in
37
Si.
Members of the epidermal growth factor receptor (EGFR) subfamily of receptor protein tyrosine kinases have been implicated in the pathogenesis of various malignancies. The ability of one EGFR ...subfamily member to influence, or function synergistically with, another is likely to be a general feature of these receptors. To assess the role of receptor heterodimerization, we analyzed the ability of Neu differentiation factor (NDF) to induce cell growth and transformation of NIH 3T3 cells transfected with different combinations of the EGFR subfamily of receptors. NDF induced mitogenesis, but not transformation, of cells expressing either HER3 or HER4 alone. However, NDF-induced cell transformation was observed when either HER1 or HER2 was coexpressed with HER3 or HER4. In analogous receptor phosphorylation experiments, NDF-induced transphosphorylation appears to be correlated with synergistic transformation of NIH 3T3 cells. Interestingly, transphosphorylation between HER1 and HER4 can be stimulated by either EGF or NDF.
A new isomer with a half-life of 23.0(8) ms has been identified at 2406 keV in (126)Pd and is proposed to have a spin and parity of 10(+) with a maximally aligned configuration comprising two neutron ...holes in the 1h(11/2) orbit. In addition to an internal-decay branch through a hindered electric octupole transition, β decay from the long-lived isomer was observed to populate excited states at high spins in (126)Ag. The smaller energy difference between the 10(+) and 7(-) isomers in (126)Pd than in the heavier N=80 isotones can be interpreted as being ascribed to the monopole shift of the 1h(11/2) neutron orbit. The effects of the monopole interaction on the evolution of single-neutron energies below (132)Sn are discussed in terms of the central and tensor forces.
A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the ...development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c-kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility.
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