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: Androgen-independent prostate cancer is today an incurable disease, but increased understanding of the mechanisms for the transition into an androgen-independent state may increase the possibilities for more efficient strategies in the future.', 'An androgen-independent subline, LNCaP-19, to the androgen-dependent prostate cancer cell line LNCaP was developed in vitro under standard culture conditions. The characteristics of LNCaP-19 regarding androgen responsiveness, PSA, and VEGF secretion was studied in vitro. The growth in vivo and the microvessel density (MVD) of the tumors were studied after inoculation in nude mice.', 'LNCaP-19 grows equally well in dextran-charcoal stripped FBS (DCC-FBS) as in normal FBS, and rapidly gives rise to tumors in both intact and castrated mice, indicating a true androgen-independent growth. The PSA secretion from LNCaP-19 cells was lower than from LNCaP cells, while the VEGF level was comparable to the secretion from LNCaP cells without androgen stimulation. The MVD was increased in the LNCaP-19 tumors, and the vessels also displayed a changed morphology with exclusively small microvessels without lumen.
Answer: LNCaP-19 shows characteristics resembling those of androgen-independent prostate cancer. An increased MVD and changed vessel morphology in the tumor, makes it an interesting model system for studies regarding angiogenesis in the context of the acquisition of androgen independence.

Answer: Is transition of an androgen-dependent human prostate cancer cell line into an androgen-independent subline associated with increased angiogenesis?


Question: Context: Animal and human studies suggest that programing of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the development of obesity, but human studies of biological indicators of HPA axis activity are lacking. We studied the association between levels of the stress hormone cortisol during pregnancy and overweight offspring during childhood into adolescence.', 'Salivary samples from 655 Danish pregnant women with singleton pregnancies (1989-1991) were collected once in the morning and once in the evening in their second and third trimester. We followed the offspring from two to 16 years of age with at least one measurement of height and weight, and classified their body mass index into overweight and normal weight. The adjusted relative difference in median salivary cortisol (with 95% confidence interval (CI)) during pregnancy (the four samples), in second and third trimester (morning and evening samples) between overweight and normal weight offspring was estimated. Furthermore, the adjusted median ratio between morning and evening maternal salivary cortisol level was estimated for normal weight and overweight children. All the analyses were stratified into the equal age groups: 2-6, 7-11, and 12-16 years.', 'We found non-significant higher maternal cortisol levels during pregnancy in offspring that were overweight at the age of 2-6, 7-11 and 12-16 years than in normal weight peers; adjusted relative difference in median salivary cortisol 11% (95% CI: -2; 25), 6% (95% CI: -7; 20), and 9% (95% CI: -4; 24), respectively. A statistically significantly higher level of maternal cortisol was found in the second trimester in 2-6-year-old and 12-16-year-old overweight offspring; relative difference 19% (95% CI: 3; 37), and 20% (95% CI: 3; 41), respectively. The median ratio between morning and evening maternal salivary cortisol level was similar for overweight and normal weight children; e.g. at age 2-6 years in third trimester 4.31 (95% CI: 4.05; 4.60)nmol/l and 4.28 (95% CI: 3.60; 5.09)nmol/l, respectively (P=0.93).
Answer: Our findings suggest a relatively consistent association between pregnancy cortisol levels and overweight offspring, especially in the second trimester.

Answer: Are maternal salivary cortisol levels during pregnancy positively associated with overweight children?


Question: Context: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice.', 'We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level.', 'U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction.
Answer: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.

Answer:
Is low birth weight associated with adiposity , impaired skeletal muscle energetics and weight loss resistance in mice?