RNP recognition by the viral polymerase involves a specific selleck chemicals interaction between the C-terminal domain of the phosphoprotein (P) (P-CTD) and N. However, the P binding region on N remains to be identified. In this study, glutathione S-transferase (GST) pulldown
assays were used to identify the N-terminal core domain of HRSV N (N-NTD) as a P binding domain. A biochemical characterization of the P-CTD and molecular modeling of the N-NTD, allowed us to define four potential candidate pockets on N (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged regions, which could constitute sites complementary to the P-CTD interaction domain. The role of selected amino acids in the recognition of the N-RNA complex by P was first screened for by site-directed mutagenesis using a polymerase activity assay, based on an HRSV minigenome containing a luciferase reporter gene. see more When changed to Ala, most of the residues of PI were found to be critical for viral RNA synthesis,
with the R132A mutant having the strongest effect. These mutations also reduced or abolished in vitro and in vivo P-N interactions, as determined by GST pulldown and immunoprecipitation experiments. The pocket formed by these residues is critical for P binding to the N-RNA complex, is specific for pneumovirus N proteins, and is clearly distinct from the P binding sites identified so far for other nonsegmented negative-strand viruses.”
“Depression is a major issue worldwide and is seen as a significant health problem. Stigma and patient denial, clinical experience, time limitations, and reliability of psychometrics are barriers to the clinical diagnoses of depression. Thus, the establishment of an automated system
that could detect such abnormalities would assist Carbohydrate medical experts in their decision-making process. This paper reviews existing methods for the automated detection of depression from brain structural magnetic resonance images (sMRI).
Relevant sources were identified from various databases and online sites using a combination of keywords and terms including depression, major depressive disorder, detection, classification, and MRI databases. Reference lists of chosen articles were further reviewed for associated publications.
The paper introduces a generic structure for representing and describing the methods developed for the detection of depression from sMRI of the brain. It consists of a number of components including acquisition and preprocessing, feature extraction, feature selection, and classification.
Automated sMRI-based detection methods have the potential to provide an objective measure of depression, hence improving the confidence level in the diagnosis and prognosis of depression.