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.

[EX Q]: Context: BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination.', 'Mouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10-day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H.', 'BAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNFα/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312.
Answer: Overall, this study suggests that BAF312 can modulate glial cell function and attenuate demyelination, highlighting this drug as a further potential therapy in demyelinating disorders, beyond MS.
[EX A]: Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?

[EX Q]: Context: A complex network of putative molecular interactions underlies the architecture and function of cell-matrix adhesions. Most of these interactions are implicated from coimmunoprecipitation studies using expressed components, but few have been demonstrated or characterized functionally in living cells.', 'We introduce fluorescence fluctuation methods to determine, at high spatial and temporal resolution, "when" and "where" molecular complexes form and their stoichiometry in nascent adhesions (NAs). We focus on integrin-associated molecules implicated in integrin activation and in the integrin-actin linkage in NAs and show that these molecules form integrin-containing complexes hierarchically within the adhesion itself. Integrin and kindlin reside in a molecular complex as soon as adhesions are visible; talin, although also present early, associates with the integrin-kindlin complex only after NAs have formed and in response to myosin II activity. Furthermore, talin and vinculin association precedes the formation of the integrin-talin complex. Finally, α-actinin enters NAs periodically and in clusters that transiently associate with integrins. The absolute number and stoichiometry of these molecules varies among the molecules studied and changes as adhesions mature.
Answer: These observations suggest a working model for NA assembly whereby transient α-actinin-integrin complexes help nucleate NAs within the lamellipodium. Subsequently, integrin complexes containing kindlin, but not talin, emerge. Once NAs have formed, myosin II activity promotes talin association with the integrin-kindlin complex in a stoichiometry consistent with each talin molecule linking two integrin-kindlin complexes.
[EX A]: Do integrin-associated complexes form hierarchically with variable stoichiometry in nascent adhesions?

[EX Q]: Context: Degradation of the extracellular matrix by malignant tumor cells has an essential role in the process of tumor invasion and metastasis. The 2 gelatinolytic matrix metalloproteinases (MMPs) MMP-2 and MMP-9 are believed to be key enzymes in this process. We investigated the possible relationship between in situ gelatinolytic activity of MMPs and clinicopathological factors in patients with bladder cancer to clarify whether these proteins would be critical for tumor advancement in this disease.', 'We evaluated the intensity of gelatinolytic activity in 25 bladder cancer tissues by film in situ zymography (FIZ). To clarify the MMP(s) responsible for gelatinolytic activity in bladder cancer tissues we examined MMP-2 and MMP-9 expression in bladder tissues by gelatin zymography. MMP expression was also confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. We then investigated the association between MMP expression detected by gelatin zymography and the intensity of gelatinolytic activity determined by FIZ.', 'FIZ demonstrated that all tumor tissues had in situ gelatinolytic activities. There was a statistically significant correlation between the intensity of gelatinolytic activity, and tumor grade, stage, vessel invasion and cause specific survival (p <0.05). Stronger in situ gelatinolytic patterns were documented in cases with higher pro and active MMP-2 expression.
Answer: FIZ enables the direct assessment of in situ gelatinolytic activity in bladder cancer tissues. The intensity of activity appears to affect the biology of carcinoma tissues. Our results indicate a major role for MMP-2 in in situ gelatinolysis in bladder cancer.
[EX A]:
Does in situ gelatinolytic activity correlate with tumor progression and prognosis in patients with bladder cancer?