Assessing the reliability of retrospective reports of adverse childhood experiences among adolescents with documented childhood maltreatment

The literature suggests that childhood maltreatment is related to a higher probability of developing psychopathology and disease in adulthood. However, some authors have questioned the reliability of self-reports of maltreatment, suggesting that psychopathology at the time of evaluation affects self-reports. We evaluated the reliability of the self-reports of 79 young adults who were identified in childhood by Child Protective Services by comparing two moments of evaluation. Psychological and physical symptoms were tested to evaluate their interference with the reports. We found good to excellent agreement, with no significant correlation between the changes in self-reported experiences and the changes in physical and psychological symptoms, suggesting that the reliability of reports is not related to the health state at the time of the report

PROlocalizer: integrated web service for protein subcellular localization prediction

Subcellular localization is an important protein property, which is related to function, interactions and other features. As experimental determination of the localization can be tedious, especially for large numbers of proteins, a number of prediction tools have been developed. We developed the PROlocalizer service that integrates 11 individual methods to predict altogether 12 localizations for animal proteins. The method allows the submission of a number of proteins and mutations and generates a detailed informative document of the prediction and obtained results. PROlocalizer is available at http://bioinf.uta.fi/PROlocalizer/

X-ray Structures of the Signal Recognition Particle Receptor Reveal Targeting Cycle Intermediates

The signal recognition particle (SRP) and its conjugate receptor (SR) mediate cotranslational targeting of a subclass of proteins destined for secretion to the endoplasmic reticulum membrane in eukaryotes or to the plasma membrane in prokaryotes. Conserved active site residues in the GTPase domains of both SRP and SR mediate discrete conformational changes during formation and dissociation of the SRP·SR complex. Here, we describe structures of the prokaryotic SR, FtsY, as an apo protein and in two different complexes with a non-hydrolysable GTP analog (GMPPNP). These structures reveal intermediate conformations of FtsY containing GMPPNP and explain how the conserved active site residues position the nucleotide into a non-catalytic conformation. The basis for the lower specificity of binding of nucleotide in FtsY prior to heterodimerization with the SRP conjugate Ffh is also shown. We propose that these structural changes represent discrete conformational states assumed by FtsY during targeting complex formation and dissociation

Structural and functional basis for RNA cleavage by Ire1

BACKGROUND: The unfolded protein response (UPR) controls the protein folding capacity of the endoplasmic reticulum (ER). Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase) domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. RESULTS: This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing \u3e/=7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL) of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. CONCLUSIONS: Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L

In Re: Experimental Education

This chapter appeared in a volume that summarized the results of the three-year "Patterns of Intuition" project that Gerhard Nierhaus and others directed: the project investigated the creative act of composing by means of algorithmic composition. Central to the investigation were the compositional strategies of twelve composers, which were documented through a dialogic and cyclic process of modelling and evaluating musical materials. In the second part of the book contributions by various authors considered the project from different perspectives, offered independent approaches, or provided more general reflections from their respective research fields. The present chapter situates the project in the context of experimental practice in music, especially in the tradition of pragmatist aesthetics and education best represented in the writings of John Dewey