Structural analysis of p185c-neu and epidermal growth factor receptor tyrosine kinases: oligomerization of kinase domains

The epidermal growth factor receptor (EGFR) and p185c-neu proteins associate as dimers to create an efficient signaling assembly. Overexpression of these receptors together enhances their intrinsic kinase activity and concomitantly results in oncogenic cellular transformation. The ectodomain is able to stabilize the dimer, whereas the kinase domain mediates biological activity. Here we analyze potential interactions of the cytoplasmic kinase domains of the EGFR and p185c-neu tyrosine kinases by homology molecular modeling. This analysis indicates that kinase domains can associate as dimers and, based on intermolecular interaction calculations, that heterodimer formation is favored over homodimers. The study also predicts that the self-autophosphorylation sites located within the kinase domains are not likely to interfere with tyrosine kinase activity, but may regulate the selection of substrates, thereby modulating signal transduction. In addition, the models suggest that the kinase domains of EGFR and p185c-neu can undergo higher order aggregation such as the formation of tetramers. Formation of tetrameric complexes may explain some of the experimentally observed features of their ligand affinity and hetero-receptor internalization.     

Epidemiology of clonorchiasis in Ninh Binh Province, Vietnam

We present the spatial structure of binase, a small extracellular ribonuclease, derived from 1H-NMR* data in aqueous solution. The total of 20 structures were obtained via torsion angle dynamics using DYANA program with experimental NOE and hydrogen bond distance constraints and phi and chi1 dihedral angle constraints. The final structures were energy minimised with ECEPP/2 potential in FANTOM program. Binase consists of three alpha-helices in N-terminal part (residues 6-16, 26-32 and 41-44), five-stranded antiparallel beta-sheet in C-terminal part (residues 51-55, 70-75, 86-90, 94-99 and 104-108) and two-stranded parallel beta-sheet (residues 22-24 and 49-51). Three loops (residues 36-39, 56-67 and 76-83), which play significant role in biological functioning of binase, are flexible in solution. The differences between binase and barnase spatial structures in solution explain the differences in thermostability of binase, barnase and their hybrids.     

Relationship between dishabituation, sensitization, and inhibition of the gill- and siphon-withdrawal reflex in Aplysia californica: Effects of response measure, test time, and training stimulus.

Previous studies have raised questions about the relationships between habituation, dishabituation, sensitization, and inhibition of reflex responses. To explore this issue further, a systematic study of these simple forms of learning was carried out in unrestrained Aplysia in which the amplitude as well as the duration of both the gill- and siphon-withdrawal reflexes were measured after either tailshock or mantle shock. The results suggest that transient reflex inhibition is not an invariant effect of noxious stimulation but depends instead on the response measure, test time, and type of noxious stimulus. Furthermore, the results suggest that dishabituation and sensitization may not involve different processes at the behavioral level; rather the observed differences between them may be due largely to an interaction between habituation and inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of psychopathology and demographic characteristics on MMPI-2 scale scores

Using multiple linear regression analyses, we examined the effects of subject status for 6 demographic variables and the presence of psychopathology on variance in MMPI-2 scale scores. The analyses were designed to measure the incremental contribution of the demographic variables to scale variance beyond that explained by presence of psychopathology. Demographic variables were found to contribute little incremental variance for the validity and clinical scales, but did explain more than 10% of the score variance for 1 clinical scale, 2 content scales, and 5 supplemental scales. For these 8 scales, gender was most often the potent demographic variable and an expected influence. The results are discussed in light of the use of gender-based norms and in terms of other potential factors that might explain MMPI-2 scale score variance.     

Inequivalence of the two tyrosine ligands in the N-lobe of human serum transferrin

Human serum transferrin N-lobe (hTF/2N) has four iron-binding ligands, including one histidine, one aspartate, and two tyrosines. The present report elucidates the inequivalence of the two tyrosine ligands (Tyr 95 and Tyr 188) on the metal-binding properties of hTF/2N by means of site-directed mutagenesis, metal release kinetics, and absorption and electron paramagnetic resonance (EPR) spectroscopies. When the liganding tyrosines were mutated individually to phenylalanine, the resulting mutant Y95F showed a weak binding affinity for iron and no affinity for copper, whereas, mutant Y188F completely lost the ability to bind iron but formed a stable complex with copper. Since other studies have demonstrated that mutations of the other two ligands, histidine and aspartate, did not completely abolish iron binding, the present findings suggest that the tyrosine ligand at position 188 is essential for binding of iron to occur. Replacement of Tyr 188 with phenylalanine created a favorable chemical environment for copper coordination but a fatal situation for iron binding. The positions of the two liganding tyrosines in the metal-binding cleft suggest a reason for the inequivalence.     

Boron diffusion and penetration in ultrathin oxide with poly-Sigate

Boron penetration through thin gate oxide down to 17 Å is investigated in this work. Boron penetration is characterized by the amount of flat band shift in a MOS capacitor. The effective diffusion coefficient of boron in these thin oxides is found to be higher than in thicker oxides. The introduction of a moderate dose of fluorine (1×10¹⁵ cm^-2) during gate doping enhances boron penetration in these thin oxides. Compared to as-deposited polycrystalline silicon (poly-Si), crystallized amorphous silicon (α-Si) films display slower boron diffusion in the gate and reduce enhancement of boron penetration due to fluorine. However, crystallized α-Si gate also reduces the amount of dopant activation and leads to extra gate depletion. The tradeoff between dopant activation and boron penetration is discussed     

Complexes of starch polysaccharides and poly(ethylene co-acrylic acid): Structure and stability in solution

Chiroptical methods have been used to study the conformation and interactions of amylose and amylopectin with poly(ethylene co-acrylic acid) (EAA) in aqueous solution. These studies, along with X-ray diffraction and solid-state NMR data, show that amylose and EAA, as well as amylopectin and EAA, form helical V-type inclusion complexes when mixed in aqueous suspension. This structure apparently accounts for the partial compatibility observed in films containing starch and EAA. About 2/3 by weight of EAA does not interact with amylose and probably represents the ethylene-rich central core of the EAA micelle. EAA/amylose complexes in 10 mM NaOH were stable to temperatures > 90°C, whereas EAA/amylopectin complexes in the same solvent were largely disrupted at this temperature. Urea, at a concentration of 8 M, further destabilized both EAA/amylopectin and EAA/amylose complexes. Solutions with an alkaline pH (> 9.5) dispersed EAA optimally and allowed maximum complexing with amylose. At pH values > 13, the EAA/amylose complexes were weaker, most likely due to electrostatic repulsion between ionized hydroxyl groups of amylose and carboxyl groups of EAA.