Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Ex Input:
Previous research in fetuses with increased nuchal translucency (NT) showed abnormal lymphatic endothelial differentiation characteristics, including increased vascular endothelial growth factor (VEGF)-A expression, and aberrant smooth muscle cells (SMCs) surrounding enlarged jugular lymphatic sacs (JLS). We hypothesized that abnormal Sonic hedgehog (Shh) expression would result in altered VEGF-A signaling in the lymphatic endothelial cells of the JLS and that aberrant acquisition of SMCs could be caused by downregulation of forkhead transcription factor FOXC2 and upregulation of platelet-derived growth factor (PDGF)-B in the lymphatic endothelial cells of the JLS.', 'Five trisomy 21 fetuses and four controls were investigated using immunohistochemistry for Shh, VEGF-A, FOXC2 and PDGF-B expression in the lymphatic endothelial cells of the JLS.', 'An increased Shh, VEGF-A and PDGF-B expression, and decreased FOXC2 expression were shown in the lymphatic endothelial cells of the JLS of the trisomic fetuses.

Ex Output:
Does abnormal Shh and FOXC2 expression correlate with aberrant lymphatic development in human fetuses with increased nuchal translucency?


Ex Input:
Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.

Ex Output:
Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?


Ex Input:
While glucocorticoids and the liganded glucocorticoid receptor (GR) have a well-established role in the maintenance of differentiation and suppression of apoptosis in breast tissue, the involvement of unliganded GR in cellular processes is less clear. Our previous studies implicated unliganded GR as a positive regulator of the BRCA1 tumour suppressor gene in the absence of glucocorticoid hormone, which suggested it could play a similar role in the regulation of other genes.', 'An shRNA vector directed against GR was used to create mouse mammary cell lines with depleted endogenous levels of this receptor in order to further characterize the role of GR in breast cells. An expression microarray screen for targets of unliganded GR was performed using our GR-depleted cell lines maintained in the absence of glucocorticoids. Candidate genes positively regulated by unliganded GR were identified, classified by Gene Ontology and Ingenuity Pathway Analysis, and validated using quantitative real-time reverse transcriptase PCR. Chromatin immunoprecipitation and dual luciferase expression assays were conducted to further investigate the mechanism through which unliganded GR regulates these genes.', 'Expression microarray analysis revealed 260 targets negatively regulated and 343 targets positively regulated by unliganded GR. A number of the positively regulated targets were involved in pro-apoptotic networks, possibly opposing the activity of liganded GR targets. Validation and further analysis of five candidates from the microarray indicated that two of these, Hsd11b1 and Ch25h, were regulated by unliganded GR in a manner similar to Brca1 during glucocorticoid treatment. Furthermore, GR was shown to interact directly with and upregulate the Ch25h promoter in the absence, but not the presence, of hydrocortisone (HC), confirming our previously described model of gene regulation by unliganded GR.

Ex Output:

Does expression microarray identify the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells?