Trans receptor inhibition of human glioblastoma cells by erbB family ectodomains

Our aim has been to understand the features of erbB receptor homo- and heterodimer assembly to develop approaches to disrupt receptor activation. We have developed a general approach to cause erbB receptor-specific trans inhibition of human neoplasia. The clonal progression of human astrocytomas to a more malignant phenotype often involves the amplification and overexpression of the epidermal growth factor receptor (EGFr) gene. We have selectively targeted the EGFr in human glioblastoma cells with kinase-deficient mutants of the erbB family derived from the ectodomain of the Neu oncogene that are able to form heterodimers with EGFr and inhibit EGFr-dependent phenotypes. In EGFr-positive U87MG human glioblastoma cells, expression of the Neu ectodomain inhibits EGF-, but not platelet-derived growth factor-, induced DNA synthesis; inhibits cell proliferation in the presence of EGF, but not platelet-derived growth factor; inhibits the ability of U87MG to form colonies in soft agar; and inhibits transforming efficiency in athymic mice. These studies establish that EGFr-mediated signal transduction is important in the maintenance of malignant glioma, and that trans receptor inhibition is a novel way to abrogate abnormal growth of these tumors. Neu ectodomains will be useful in determining the manner in which the EGFr contributes to glial tumorigenesis and in the design of pharmaceuticals that disable erbB family oncoproteins. In addition, these studies provide a rationale for the application of the Neu ectodomain in gene therapy approaches to human malignant glioma and, potentially, to other systemic epithelial malignancies expressing erbB family receptors.     

A single mutation that increases maize seed weight

The maize endosperm-specific gene shrunken2 (Sh2) encodes the large subunit of the heterotetrameric starch synthetic enzyme adenosine diphosphoglucose pyrophosphorylase (AGP; EC 2.7.7.27). Here we exploit an in vivo, site-specific mutagenesis system to create short insertion mutations in a region of the gene known to be involved in the allosteric regulation of AGP. The site-specific mutagen is the transposable element dissociation (Ds). Approximately one-third (8 of 23) of the germinal revertants sequenced restored the wild-type sequence, whereas the remaining revertants contained insertions of 3 or 6 bp. All revertants retained the original reading frame 3' to the insertion site and involved the addition of tyrosine and/or serine. Each insertion revertant reduced total AGP activity and the amount of the SH2 protein. The revertant containing additional tyrosine and serine residues increased seed weight 11-18% without increasing or decreasing the percentage of starch. Other insertion revertants lacking an additional serine reduced seed weight. Reduced sensitivity to phosphate, a long-known inhibitor of AGP, was found in the high seed-weight revertant. This alteration is likely universally important since insertion of tyrosine and serine in the potato large subunit of AGP at the comparable position and expression in Escherichia coli also led to a phosphate-insensitive enzyme. These results show that single gene mutations giving rise to increased seed weight, and therefore perhaps yield, are clearly possible in a plant with a long history of intensive and successful breeding efforts.     

Mirror effect in frequency discrimination

In recognition, types of stimuli that are relatively easy to classify as old when old are also relatively easy to classify as new when new. The experiments reported here extend this mirror effect to discriminations among above-zero situational frequencies. Frequency discrimination exhibits a mirror effect when words are compared with nonwords or when low-linguistic-frequency words are compared with high-linguistic-frequency words. Accurate knowledge concerning the relative memorability of test items is neither necessary nor sufficient for the presence of a mirror effect.     

Reactivity in infants: A cross-national comparison.

433 4-mo-old infants from Boston, Dublin, and Beijing were administered the same battery of visual, auditory, and olfactory stimuli to evaluate differences in levels of reactivity. The Chinese Ss were significantly less active, irritable, and vocal than the Boston and Dublin samples, with Boston Ss showing the highest level of reactivity. Data suggest the possibility of temperamental differences between Caucasian and Asian infants in reactivity to stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low-threshold (Ga,In)(As,P) d.h. lasers emitting at 1.55 ?m grown by l.p.e.

Threshold current densities as low as 2.13 kA cm?2 have been achieved in broad-contact double-heterostructure lasers with an emission wavelength of 1.55 ?m. The three-layer structure was grown by liquid-phase epitaxy and contained a quaternary active layer 0.6 ?m thick and a p-type quaternary upper confining layer with a bandgap of 1.05 eV. The normalised threshold current density was 3.5 kA cm?2 ?m?1.