Predicting Addiction Severity Index (ASI) interviewer severity ratings for a computer-administered ASI.

The Addiction Severity Index (ASI) is a reliable and valid measure of problem severity among addicted patients. Concerns have been raised about the reliability of the Interviewer Severity Rating (ISR), a summary score for each of 7 domains. As part of an effort to build a computer-administered ASI, regression equations were developed to predict the ISR. Repeated resampling of a large dataset, consisting of 1,124 ASIs conducted by trained interviewers, permitted derivation of stable regression equations predicting the ISR for each ASI domain from patients' answers to preselected interview items. The resulting 7 Predicted Severity Ratings (PSRs) were tested on 8, standardized vignettes, with "gold standard," expert-generated ISRs. Reliabilities compared well with those of intensively trained interviewers. The PSRs could provide an alternative to potentially unreliable interviewer ratings, enhancing the ASI's role in treatment planning and treatment matching and make possible a computer-administered version of the ASI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The structure of cyclin H: common mode of kinase activation and specific features

The crystal structure of human cyclin H refined at 2.6 A resolution is compared with that of cyclin A. The core of the molecule consists of two repeats containing five helices each and forming the canonical cyclin fold also observed in TFIIB. One hundred and thirty-two out of the 217 C alpha atoms from the cyclin fold can be superposed with a root-mean-square difference of 1.8 A. The structural homology is even higher for the residues at the interface with the kinase, which is of functional significance, as shown by our observation that cyclin H binds to cyclin-dependent kinase 2 (cdk2) and that cyclin A is able to activate cdk7 in the presence of MAT1. Based on this superposition, a new signature sequence for cyclins was found. The specificity of the cyclin H molecule is provided mainly by two long helices which extend the cyclin fold at its N- and C-termini and pack together against the first repeat on the side opposite to the kinase. Deletion mutants show that the terminal helices are required for a functionally active cyclin H.     

Empirically supported treatments: Implications for training.

This article discusses the role of empirically supported treatments (ESTs) in the training of clinical psychologists. Training in ESTs can be integrated in ways that vary depending on the level of training and setting. Predoctoral programs, internships, postdoctoral programs, and continuing education are discussed in regard to special challenges and sequencing of training. A preliminary set of guidelines for training in ESTs is suggested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coordinated amino acid changes in homologous protein families

In the tobamovirus coat protein family, amino acid residuesat some spatially close positions are found to be substitutedin a coordinated manner [Altschuh et al. (1987) J. Mol. Biol.,193,693]. Therefore, these positions show an identical patternof amino acid substitutions when amino acid sequences of thesehomologous proteins are aligned. Based on this principle, coordinatedsubstitutions have been searched for in three additional proteinfamilies: serine proteases, cysteine proteases and the haemoglobins.Coordinated changes have been found in all three protein familiesmostly within structurally constrained regions. This methodworks with a varying degree of success depending on the functionof the proteins, the range of sequence similarities and thenumber of sequences considered. By relaxing the criteria forresidue selection, the method was adapted to cover a broaderrange of protein families and to study regions of the proteinshaving weaker structural constraints. The information derivedby these methods provides a general guide for engineering ofa large variety of proteins to analyse structure–functionrelationships.     

Monitoring ligand modulation of protein-protein interactions by mass spectrometry: estrogen receptor alpha-SRC1

Many drugs and chemicals exert their biological effect by modulating protein-protein interactions. In vitro approaches to characterize these mechanisms are often based on indirect measurements (e.g., fluorescence). Here, we used mass spectrometry (MS) to directly monitor the effect of small-molecule ligands on the binding of a coactivator peptide (SRC1) by the human estrogen receptor alpha ligand binding domain (hERalpha LBD). Nanoelectrospray mass spectrometry (nanoESI-MS) and high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with chemical cross-linking were employed to follow these processes. The chemical cross-linking protocol used prior to high-mass MALDI analysis allows detection of intact noncovalent complexes. The binding of intact hERalpha LBD homodimer with two coactivator peptides was detected with nanoESI-MS and high-mass MALDI-MS only in the presence of an agonist ligand. Furthermore, high-mass MALDI-MS revealed an increase of the homodimer abundance after incubating the receptor with a ligand, independent of the ligand character (i.e., agonist, antagonist). The binding characteristics of the compounds tested by MS correlate very well with their biological activity reported by cell-based assays. High-mass MALDI appears to be an efficient and simple tool for directly monitoring ligand regulation mechanisms involved in protein-protein interactions. Furthermore, the combination of both MS methods allows identifying and characterizing endocrine-disrupting compounds or new drug compounds in an efficient way.