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.

[EX Q]: Context: Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies.', 'To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure.
Answer: GDF-15 carries information on CV dysfunction and disease that is not captured by traditional CV risk factors in elderly individuals.
[EX A]: Is growth-differentiation factor-15 an independent marker of cardiovascular dysfunction and disease in the elderly : results from the Prospective Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) Study?

[EX Q]: Context: Hypospadias is a common male congenital urethral malformation, defined as the displacement of the urethral meatus ventrally from the tip of the glans penis. The importance of androgen receptor in male external genitalia development has been well recognized. Recently, the presence of active estrogen receptors (ER) in the developing male external genitalia has also been demonstrated. There are two isoforms of the human estrogen receptor, ESR1 and ESR2, which occur, with distinct tissue and cell patterns of expression. We hypothesized that modifications in these nuclear receptors' genes could lead to hypospadias.", 'We screened 60 boys with hypospadias for mutations in the coding regions of ESR1 and ESR2 genes, by denaturing high-performance liquid chromatography and automated sequence analysis. We also genotyped the CA repeat polymorphism in ESR2 and the TA repeat polymorphism in ESR1.', 'The CA repeat polymorphism in ESR2 is prolonged in hypospadias patients compared to controls (p < 0.05). Prolongation of this CA repeat polymorphism has previously been associated with lower levels of testosterone. Six patients presented the genetic variant 2681-4A > G (rs944050) in the heterozygous form in ESR2, which was a significantly higher frequency than in the control population (p < 0.05). One of these patients also presented a 266_267insC in exon 1 of ESR2, which is also a known single nucleotide polymorphism (SNP; rs3832949). In ESR1, no significant gene alteration was found to be associated with hypospadias.
Answer: Our results suggest that variations in the ESR2 might influence susceptibility to hypospadias.
[EX A]: Are polymorphisms of estrogen receptor beta gene associated with hypospadias?

[EX Q]: Context: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive.', 'Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis.', 'Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1.
Answer: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.
[EX A]:
Is pKCε a negative regulator of PVAT-derived vessel formation?