Given a passage with a context and an answer, 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.

Q: Context: Reactive oxygen species have been implicated as signaling molecules modulating the activity of redox-sensitive transcription factors such as nuclear factor kappa B (NF-kappaB). Recently, the transcription factor hypoxia-inducible factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore aimed to elucidate the link between these 2 important redox-sensitive transcription factors.', 'In pulmonary artery smooth muscle cells, reactive oxygen species generated either by exogenous H2O2 or by a NOX4-containing NADPH oxidase stimulated by thrombin activated or induced NF-kappaB and HIF-1alpha. The reactive oxygen species-mediated HIF-1alpha induction occurred on the transcriptional level and was dependent on NF-kappaB. Transfection experiments with wild-type or mutant HIF-1alpha promoter constructs revealed the presence of a yet unidentified NF-kappaB binding element. Gel shift analyses and chromatin immunoprecipitation verified binding of NF-kappaB to this site. Furthermore, reactive oxygen species enhanced expression of plasminogen activator inhibitor-1, which was prevented by dominant-negative IkappaB or mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 promoter.
Answer: These findings show for the first time to our knowledge that reactive oxygen species directly link HIF-1alpha and NF-kappaB, implicating an important pathophysiological role of this novel pathway in disorders associated with elevated levels of reactive oxygen species.

A: Do reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site?
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Q: Context: Eph receptors, comprising the A- and B-subfamilies, are the largest family of receptor tyrosine kinases in the mammalian genome, and their function is critical for morphogenesis in a variety of contexts. Whereas signaling through B-type Ephs has been demonstrated to play a role in cleft lip and palate (CL/P), the involvement of A-type Ephs has not been examined in this context notwithstanding a recent genome-wide association study that identified the EPHA3 locus as a candidate for non-syndromic CL/P.', 'Here, we present a systematic analysis of the gene expression patterns for the nine EphA receptors at progressive stages of mouse development and find that EphA3, EphA4, and EphA7 exhibit restricted overlapping patterns of expression during palate development. We find that homozygous mutation of EphA3 or compound homozygous mutation of EphA3 and EphA4 in mice does not result in defective midfacial development, supporting the possibility of redundant function with EphA7. We also document previously undescribed expression patterns in other tissues of the craniofacial complex including the lacrimal duct and salivary glands.
Answer: Together, these results are consistent with the hypothesis that mutations in EPHA family genes may cause CL/P and also suggest that functional redundancy between family members may be at play.

A: Does embryonic expression of EphA receptor genes in mice support their candidacy for involvement in cleft lip and palate?
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Q: Context: Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft-versus-host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate.', 'This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: (1) severe PE (n = 10), (2) severe PE complicated with SGA (n = 10), (3) SGA without PE (n = 10), and (4) controls (n = 10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis.', '(1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels, and the villous stroma. (2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47-fold, p = 0.004; 1.44-fold, p = 0.003, respectively) and in SGA (1.68-fold, p = 0.001; 1.64-fold, p = 0.001, respectively). (3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining.
Answer: (1) We report for the first time the placental expression and localization of galectin-1 mRNA and demonstrate that the protein is abundantly present in third trimester human placentas. (2) Placental galectin-1 expression is higher in severe PE than in normal pregnancy regardless of the presence of SGA. (3) However, it is not altered in SGA without PE. We propose that the increased placental expression of galectin-1 in patients with severe PE may represent a fetal response to an exaggerated systemic maternal inflammation; thus, galectin-1 may be implicated in maternal-fetal immune tolerance in humans.

A:
Is severe preeclampsia characterized by increased placental expression of galectin-1?
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