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Myc proteins are transcription factors crucial for cell proliferation. They have a C-terminal domain that mediates Max and DNA binding, and an N-terminal disordered region culminating in the transactivation domain (TAD). The TAD participates in many protein– protein interactions, notably with kinases that promote stability (Aurora-A) or degradation (ERK1, GSK3) via the ubiquitin-proteasome system. We probed the structure, dynamics and interactions of N-myc TAD using nuclear magnetic resonance (NMR) spectroscopy following its complete backbone assignment. Chemical shift analysis revealed that Nmyc has two regions with clear helical propensity: Trp77–Glu86 and Ala122–Glu132. These regions also have more restricted ps–ns motions than the rest of the TAD, and, along with the phosphodegron, have comparatively high transverse (R2) 15N relaxation rates, indicative of slower timescale dynamics and/or chemical exchange. Collectively these features suggest differential propensities for structure and interaction, either internal or with binding partners, across the TAD. Solution studies on the interaction between Nmyc and Aurora-A revealed a previously uncharacterised binding site. The specificity and kinetics of sequential phosphorylation of N-myc by ERK1 and GSK3 were characterised using NMR and resulted in no significant structural changes outside the phosphodegron. When the phosphodegron was doubly phosphorylated, N-myc formed a robust interaction with the Fbxw7–Skp1 complex, but mapping the interaction by NMR suggests a more extensive interface. Our study provides foundational insights into N-myc TAD dynamics and a backbone assignment that will underpin future work on the structure, dynamics, interactions and regulatory post-translational modifications of this key oncoprotein. [ABSTRACT FROM AUTHOR]

It has taken 17 years from the first identification of a voltage-gated [Ca.sup.2+] channel ([Ca.sub.v]) [beta]-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of [Ca.sup.2+] channel [beta]-subunits. Three recent X-ray crystallographic studies have now solved the structures of the core domains of three [Ca.sup.2+] channel [beta]-subunits. In this article, the properties of these cytoplasmic auxiliary subunits will first be summarized. Then the [Ca.sub.v][beta] structures and the information they provide regarding how these proteins interact with the [Ca.sub.v][alpha]1 subunit will be discussed and the possible implications of these new data for G-protein modulation of [Ca.sup.2+] channels will be examined.

Aluminum is one type of metal base material used as an alternative to acrylic resin. This study evaluated whether commonly used denture cleansers cause leaching of the metal base into the cleaning solution. Seven cleansers (Efferdent, Polident, Clorox, Clorox/Cascade, vinegar, Tartar and Stain Remover, and Ivory soap) and two controls (tap water and distilled water) were evaluated. One hundred thirty-five wax samples (30 × 30 × 1 mm) were cast in 99.4% pure aluminum. The 135 samples were randomly assigned to the nine cleanser groups. Each sample was soaked in a cleanser for 0.5, 1, or 8 hours, and the amount of aluminum present in each cleanser was then analyzed by atomic flame-emission spectrometry. The results indicated that all cleansers leached aluminum into solution in varying amounts. Tartar and Stain Remover and Clorox caused the greatest leaching, whereas Ivory soap and Efferdent leached the least. [ABSTRACT FROM AUTHOR]

This study investigated the early erosion of glass ionomer-cement that had been used to lute complete east crowns. Restorations had margins ending on either enamel or cementum and had various sizes of marginal openings. These restorations were compared to those using a standard zinc phosphate cement Results showed that leaving the band of excess cement, expressed during the seating of the crown, undisturbed for 10 minutes prevented significant erosion in a wet field. A resin coat was not necessary to provide further protection after removal of the band Zinc phosphate cement also showed significant early erosion when exposed to moisture. [ABSTRACT FROM AUTHOR]

A computer program that uses cephalometric analyses for determining the patient's occlusal vertical dimension has recently been introduced. Data generated from this computer implies changes in incisal-pin position for articulated casts. This study evaluated the accuracy of this vertical-dimension program using 24 completely dentate, white male subjects with clinically acceptable occlusal vertical dimensions. A cephalometric radiograph was made, and measurements from the tracing were entered into the computer for analysis. Recommended incisal-pin changes ranged from -11 to + 25.3 mm, with a mean change of 8.4 mm for all methods tested. These results showed a low correlation with each subject's clinically determined occlusal vertical dimension. [ABSTRACT FROM AUTHOR]

The CaVβ subunits of voltage-gated calcium channels regulate the trafficking and biophysical properties of these channels. We have taken advantage of mutations in the tyrosine residue within the alpha interaction domain (AID) in the I–II linker of CaV2.2 which reduce, but do not abolish, the binding of β1b to the AID of CaV2.2. We have found that the mutation Y388S decreased the affinity of CaVβ1b binding to the CaV2.2 I–II linker from 14 to 329 nm. However, the Y388S mutation had no effect on current density and cell surface expression of CaV2.2/α2δ-2/β1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore, despite the 24-fold reduced affinity of CaVβ1b for the Y388S I–II linker of CaV2.2, all the key features of modulation as well as trafficking by CaVβ subunits remained intact. This is in contrast to the much more marked effect of the W391A mutation, which abolished interaction with the CaV2.2 I–II linker, and very markedly affected the trafficking of the channels. However, using the Xenopus oocyte expression system, where expression levels can be accurately titrated, when CaVβ1b cDNA was diluted 50-fold, all evidence of interaction with CaV2.2 Y388S was lost, although wild-type CaV2.2 was still normally modulated by the reduced concentration of β1b. These results indicate that high affinity interaction with the α1 subunit is not necessary for any of the modulatory effects of CaVβ subunits, but occupancy of the interaction site is important, and this will occur, despite the reduced affinity, if the CaVβ subunit is present in sufficient excess. [ABSTRACT FROM AUTHOR]