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.
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Question: 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.

Answer: Do reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site?


Question: Context: For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.
Answer: Although assessment of children's competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad. Previous research outcomes showed that children's medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children's competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated.

Answer: Is informed consent instead of assent appropriate in children from the age of twelve : Policy implications of new findings on children 's competence to consent to clinical research?


Question: Context: Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively.', 'Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest.', 'Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4).', 'Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice.
Answer: Mid-aged and aged PRKO and wild-type mice demonstrated rapid P or 3alpha,5alpha-THP-facilitated lordosis that may be, in part, independent of activity at PRs.

Answer:
Do mid-aged and aged wild-type and progestin receptor knockout ( PRKO ) mice demonstrate rapid progesterone and 3alpha,5alpha-THP-facilitated lordosis?