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


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Context: The lung is exposed to airborne fungal spores, and fungi that colonize the oral cavity such as Candida albicans, but does not develop disease to opportunistic fungal pathogens unless the immune system is compromised. The Group IVA cytosolic phospholipase A2 (cPLA2α) is activated in response to Candida albicans infection resulting in the release of arachidonic acid for eicosanoid production. Although eicosanoids such as prostaglandins and leukotrienes modulate inflammation and immune responses, the role of cPLA2α and eicosanoids in regulating C. albicans lung infection is not understood.', 'The responses of cPLA2α(+/+) and cPLA2α(-/-) Balb/c mice to intratracheal instillation of C. albicans were compared. After challenge, we evaluated weight loss, organ fungal burden, and the recruitment of cells and the levels of cytokines and eicosanoids in bronchoalveolar lavage fluid. The ability of macrophages and neutrophils from cPLA2α(+/+) and cPLA2α(-/-) mice to recognize and kill C. albicans was also compared.', 'After C. albicans instillation, cPLA2α(+/+) mice recovered a modest weight loss by 48\xa0h and completely cleared fungi from the lung by 12\xa0h with no dissemination to the kidneys. In cPLA2α(-/-) mice, weight loss continued for 72\xa0h, C. albicans was not completely cleared from the lung and disseminated to the kidneys. cPLA2α(-/-) mice exhibited greater signs of inflammation including higher neutrophil influx, and elevated levels of albumin and pro-inflammatory cytokines/chemokines (IL1α, IL1β, TNFα, IL6, CSF2, CXCL1, CCL20) in bronchoalveolar lavage fluid. The amounts of cysteinyl leukotrienes, thromboxane B2 and prostaglandin E2 were significantly lower in bronchoalveolar lavage fluid from C. albicans-infected cPLA2α(-/-) mice compared to cPLA2α(+/+) mice. Alveolar macrophages and neutrophils from uninfected cPLA2α(-/-) mice exhibited less killing of C. albicans in vitro than cells from cPLA2α(+/+) mice. In addition alveolar macrophages from cPLA2α(-/-) mice isolated 6\xa0h after instillation of GFP-C. albicans contained fewer internalized fungi than cPLA2α(+/+) macrophages.
Answer: The results demonstrate that cPLA2α contributes to immune surveillance and host defense in the lung to prevent infection by the commensal fungus C. albicans and to dampen inflammation.
answer:
Does cytosolic phospholipase A2 contribute to innate immune defense against Candida albicans lung infection?


question:
Context: Hyperphosphatemia, elevated calcium x phosphorus product (Ca x P), and calcium burden, major causes of vascular calcification, are correlated with increased cardiovascular morbidity and mortality in dialysis patients.', 'To address the underlying mechanisms responsible for these findings, we have utilized an in vitro human smooth muscle cell (HSMC) model of vascular calcification. Previous studies using this system demonstrated enhanced calcification of HSMC cultures treated with phosphorus levels in the hyperphosphatemic range, and implicated a sodium-dependent phosphate cotransport-dependent mechanism in this effect. In the present study, we examine the effect of increasing calcium concentrations on HSMC calcification in vitro.', 'Increasing calcium to levels observed in hypercalcemic individuals increased mineralization of HSMC cultures under normal phosphorus conditions. Importantly, at these total calcium concentrations, ionized calcium levels increased from 1.2 mmol/L to 1.7 mmol/L, consistent with levels observed physiologically in normocalcemic and hypercalcemic individuals, respectively. Furthermore, increasing both calcium and phosphorus levels led to accelerated and increased mineralization in the cultures. Calcium-induced mineralization was dependent on the function of a sodium-dependent phosphate cotransporter, since it was inhibited by phosphonoformic acid (PFA). While elevated calcium did not affect short-term phosphorus transport kinetics, long-term elevated calcium treatment of HSMCs induced expression of the sodium-dependent phosphate cotransporter, Pit-1.
Answer: These studies suggest that elevated calcium may stimulate HSMC mineralization by elevating Ca x P product and enhancing the sodium-dependent phosphate cotransporter-dependent mineralization pathway previously observed in HSMCs.
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Do elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro?