TASK DEFINITION: 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.
PROBLEM: To conduct clinical and genetic studies in a European family with autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to investigate the functional consequences of a novel ELOVL4 mutation.', 'Ophthalmic examination and mutation screening by direct sequencing of the ELOVL4 gene was performed in two affected individuals. Wild-type and mutant ELOVL4 genes were expressed as enhanced green fluorescent protein (EGFP) fusion proteins in transient transfection in NIH-3T3 and HEK293 cells. To determine the subcellular localization of ELOVL4, an endoplasmic-reticulum (ER)-specific marker for pDsRed2-ER was cotransfected with ELOVL4 constructs. Transfected cells were viewed by confocal microscopy. Western blot analysis was performed to assess protein expression using an anti-GFP antibody.', 'Affected patients exhibited macular atrophy with surrounding flecks characteristic of adSTGD-like MD. A novel ELOVL4 p.Tyr270X mutation was detected in affected individuals. In cell-transfection studies, wild-type ELOVL4 localized preferentially to the ER. In contrast, the mutant protein appeared to be mislocalized within transfected cells.

SOLUTION: Does a novel mutation in the ELOVL4 gene cause autosomal dominant Stargardt-like macular dystrophy?

PROBLEM: Hepatocyte nuclear factor 4α (HNF4α) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4α in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4α expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4α levels were even lower in metastatic HCCs, and ectopic HNF4α expression suppressed the metastasis of hepatoma cells both in vitro and in vivo. Forced HNF4α expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-κB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4α on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4α, which repressed RelA expression by way of interaction with RelA-3' untranslated region (UTR). In addition, nuclear factor kappa B (NF-κB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4α levels through down-regulating HNF4α-3'UTR activity.

SOLUTION: Does hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulate liver cancer progression?

PROBLEM: We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism or inguinal hernia.', 'A total of 200 patients with posterior urethral valves treated between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed.', 'Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mumol/l (range 38 to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mumol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common in cases diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027).

SOLUTION:
Are posterior urethral valves often associated with cryptorchidism and inguinal hernias?