TASK DEFINITION: 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.
PROBLEM: Context: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.', 'Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.
Answer: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.

SOLUTION: Does dll1 haploinsufficiency in adult mice lead to a complex phenotype affecting metabolic and immunological processes?

PROBLEM: Context: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).
Answer: Polymorphisms in CBR3 may explain interindividual and interethnic variability of doxorubicin pharmacokinetics and pharmacodynamics.

SOLUTION: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?

PROBLEM: Context: The main objective of the present study was the investigation of possible influence of lens opacification on macular pigment optical density (MPOD) measurements.', 'Eighty-six eyes of 64 patients (mean age 73.4 ± 8.3 years) were included in the study. MPOD was prospectively measured using the one-wavelength reflection method (Visucam500, Carl Zeiss Meditec AG) before and after cataract extraction, with implantation of a blue-light filtering intraocular lens (AlconSN60WF). The median of the maximum optical density (MaxOD) and the median of the mean optical density (MeanOD) measurements of macular pigment across the subject group were evaluated.', 'Statistically significant differences were noticed between pre-operative and post-operative measurements, the absolute values were generally lower after cataract extraction. The following median (lower/upper quartile) differences across the group were determined: MaxOD -33.8 % (-46.2 to -19.1 %), MeanOD -44.0 % (-54.6 to -26.6 %). Larger changes were observed in elderly patients [<70 years of age (n\u2009=\u200925 eyes): MaxOD -13.4 % (-20.5 to 3.6 %), MeanOD -23.6 % (-30.5 to -15.3 %) versus patients ≥70 years (n\u2009=\u200961 eyes) MaxOD -40.5 % (-53.2 to -30.1 %), MeanOD -47.2 % (-57.8 to -40.1 %)] and in patients with progressed stage of cataract. MaxOD for lens opacification grade 1 (n\u2009=\u20099 eyes): -27.4 % (-42.1 to -19.6 %), grade 2 (n\u2009=\u200926 eyes): -35.0 % (-44.2 to -25.3 %), grade 3 (n\u2009=\u200921 eyes): -34.4 % (-45.4 to -11.4 %), grade 4 (n\u2009=\u200925 eyes): -32.6 % (-53.2 to -6.4 %), and grade 5 (n\u2009=\u20095 eyes): -53.5 % (-61.7 to -38.7 %) and MeanOD for cataract stage 1 (n\u2009=\u20099 eyes): -42.6 % (-46.0 to -26.0 %), stage 2 (n\u2009=\u200926 eyes): -44.1 % (-51.8 to -26.2 %), stage 3 (n\u2009=\u200921 eyes): -45.7 % (-54.7 to -24.7 %), stage 4 (n\u2009=\u200925 eyes): -39.5 % (-59.4 to -26.1 %), and stage 5 (n\u2009=\u20095 eyes): -57.0 % (-66.1 to -51.4 %).
Answer: As established by comparison of pre- to post-operative measurements, cataract presented a strong effect on MPOD measured by one-wavelength reflection method. Particular care should therefore be taken when evaluating MPOD using this method in elderly patients with progressed stage of cataract. Future optimization of correcting parameters of scattered light and consideration of cataract influence may allow more precise evaluation of MPOD.

SOLUTION:
Does macular pigment optical density measurements by one-wavelength reflection photometry -- influence of cataract surgery on the measurement result?