Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy

Disclosure of distress among anxiety-disordered youth: Differences in treatment outcome

The present study evaluated treatment outcome differences in anxiety-disordered youth who differed in their disclosure of internal distress as measured in a structured diagnostic interview. One hundred and seventy-one clinic-referred, anxiety-disordered children served as participants. Participants\u27 primary diagnoses were one of three anxiety disorders: separation anxiety, generalized anxiety/overanxious, or social phobia/avoidance. At a pretreatment assessment, children and their parents were interviewed separately using the Anxiety Disorders Interview Schedule (ADIS) to determine the child\u27s diagnosis. The child\u27s status as a discloser of high distress or discloser of low distress was determined by the parents\u27 endorsement of an anxiety disorder and the child\u27s endorsement or lack of endorsement of an anxiety disorder, respectively. Parents, teachers, and children also completed measures assessing the child\u27s psychopathology (e.g., Revised Children\u27s Manifest Anxiety Scale, Child Behavior Checklist). In general, findings indicated that the level of distress reported by the children moderated treatment outcome. Although both groups benefited from treatment, the children disclosing high distress experienced greater treatment gains than the children disclosing low distress. © 2004 Elsevier Inc. All rights reserved

Therapy for youths with anxiety disorders: A second randomized clinical trial

Ninety-four children (aged 9-13 years) with anxiety disorders were randomly assigned to cognitive behavioral treatment or waiting-list control. Outcomes were evaluated using diagnostic status, child self-reports, parent and teacher reports, cognitive assessment and behavioral observation; maintenance was examined using 1-year follow-up data. Analyses of dependent measures indicated significant improvements over time, with the majority indicating greater gains for those receiving treatment. Treatment gains returned cases to within nondeviant limits (i.e., normative comparisons) and were maintained at 1-year follow-up. Client age and comorbid status did not moderate outcomes. A preliminary examination of treatment segments suggested that the enactive exposure (when it follows cognitive educational training) was an active force in beneficial change. Discussion includes suggestions for future research