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: The FAS/FASLG system has been proposed to play a key role in germ cell apoptosis. To elucidate the role of the genetic variants of cell death pathway genes in male infertility, we genotyped the polymorphisms of FAS, FASLG and caspase-8 (CASP8) genes and evaluated their effects on sperm apoptosis and semen quality in infertile men.', 'The genotypes of FAS, FASLG and CASP8 were determined in 620 infertile men. Sperm apoptosis rates were measured by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end labelling (TUNEL) assay, and the semen quality analysis was performed using computer assisted sperm analysis.', 'We found that polymorphisms of FAS-670A/G (rs1800682: A>G) and CASP8-652 6N ins/del (rs3834129: -/CTTACT) were associated with sperm apoptosis and semen quality. Individuals with FAS-670GG showed low apoptosis rate and decreased sperm concentration, compared with the FAS-670AA genotype. Similarly, in comparison with the CASP8-652 6N ins/ins genotype, the CASP8-652 6N (ins/del+del/del) genotypes also showed significantly decreased sperm apoptosis rate and poor sperm motility. Other polymorphisms investigated did not appear to affect sperm apoptosis and semen quality.

SOLUTION: Are polymorphisms in cell death pathway genes associated with altered sperm apoptosis and poor semen quality?

PROBLEM: Growing evidence documents elevated behavioral risk among sexual-minorities, including gay, lesbian, and bisexual individuals; however, tests of biological or psychological indicators of stress as explanations for these disparities have not been conducted.', 'Data were from the 2005-2010 National Health and Nutrition Examination Survey, and included 9662 participants; 9254 heterosexuals, 153 gays/lesbians and 255 bisexuals. Associations between sexual orientation and tobacco, alcohol, substance, and marijuana use, and body mass index, were tested using the chi-square test. Stress, operationalized as depressive symptoms and elevated C-reactive protein, was tested as mediating the association between sexual orientation and behavioral health risks. Multiple logistic regression was used to test for mediation effects, and the Sobel test was used to evaluate the statistical significance of the meditating effect.', 'Gays/lesbians and bisexuals were more likely to report current smoking (p\u2009<\u2009.001), a lifetime history of substance use (p\u2009<\u2009.001), a lifetime history of marijuana use (p\u2009<\u2009.001), and a lifetime period of risky drinking (p\u2009=\u2009.0061). The largest disparities were observed among bisexuals. Depressive symptoms partially mediated the association between sexual orientation and current smoking (aOR 2.04, 95% CI 1.59, 2.63), lifetime history of substance use (aOR 3.30 95% CI 2.20, 4.96), and lifetime history of marijuana use (aOR 2.90, 95% CI 2.02, 4.16), among bisexuals only. C-reactive protein did not mediate the sexual orientation/behavior relationship.

SOLUTION: Does stress mediate the relationship between sexual orientation and behavioral risk disparities?

PROBLEM: Expression of osteopontin correlates with tumor progression and metastasis. The mechanisms by which osteopontin promotes tumor cell survival remain unclear. Here we used short-hairpin RNA-mediated gene silencing to investigate the antitumor effects by osteopontin depletion in hepatocellular carcinoma (HCC).', 'We applied polyethylenimine nanoparticles to deliver a short-hairpin RNA for depletion of osteopontin expression in HCC cells. Tumorigenicity and metastatic potentials of HCC cells were studied in vitro and in nude mice. Nuclear factor-kappaB (NF-kappaB) activation was analyzed by gel shift assay and luciferase analysis. The expressions of integrins were examined by real-time reverse-transcription polymerase chain reaction. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and mitochondrial membrane potential analysis.', 'Down-regulation of osteopontin inhibited HCC cell growth, anchorage-independent growth, adhesion with fibronectin and invasion through extracellular matrix in vitro, and suppressed tumorigenicity and lung metastasis in nude mice. Osteopontin silencing resulted in suppression of alphav, beta1, and beta3 integrin expressions, blockade of NF-kappaB activation, inhibition of Bcl-2/Bcl-xL and XIAP expressions, increase of Bax expression, and induction of a mitochondria-mediated apoptosis. Furthermore, down-regulation of osteopontin inhibited drug-induced NF-kappaB activation and sensitized HCC cells to chemotherapeutic agents in vitro, which led to complete regression of HCC xenografts in nude mice.

SOLUTION:
Does down-regulation of osteopontin suppress growth and metastasis of hepatocellular carcinoma via induction of apoptosis?