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.

[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 TNF/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.
[A]: Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?

[Q]: Context: The modulation of intracortical inhibition is thought to be impaired in older adults, which may contribute to their reduced fine motor control, particularly during lengthening muscle contractions.', 'To quantify the magnitude of intracortical inhibition and movement performance during postural, shortening and lengthening contractions of a hand muscle in young and old adults.', 'In 18 young (23.2 4.2) and 16 old (70.6 6.5) subjects, paired-pulse transcranial magnetic stimulation (TMS) was used to assess short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) during a movement task involving the first dorsal interosseous muscle. The task required a constant load (50 g) to be slowly lifted and lowered using the index finger while single- or paired-pulse TMS was delivered during the shortening or lengthening contraction.', 'Relative to postural contractions, SICI during shortening contractions was reduced by 29% in young subjects (P < 0.0001) and 43% in old subjects (P < 0.0001), whereas SICI during lengthening contractions was reduced by 11% in young subjects (P = 0.0004) and 33% in old subjects (P < 0.0001). Furthermore, SICI was significantly less in older adults during lengthening contractions (P-values < 0.01). For LICI, inhibition was not influenced by contraction type in old subjects, but was increased by 11% during shortening contractions (P < 0.0001) and by 9% during lengthening contractions in young subjects (P = 0.0008). In addition, old subjects showed significantly less LICI than young subjects in each movement phase (both P-values < 0.05).
Answer: Shortening and lengthening contractions with a constant load are associated with a modulation of GABAergic inhibition that is altered by healthy ageing.
[A]: Is intracortical Inhibition Assessed with Paired-Pulse Transcranial Magnetic Stimulation Modulated during Shortening and Lengthening Contractions in Young and Old Adults?

[Q]: Context: To compare walking characteristics of individuals with Parkinson's disease (PD) using a new walking aid, the WalkAbout, with usual walking.", 'Fifteen subjects with PD were recruited. Subjects walked in their usual fashion and then walked again in the WalkAbout. Gait parameters, 5-min walk, and oxygen consumption were recorded.', 'Stride lengths were shorter when using the WalkAbout. On an average, the distance walked in 5 min and the oxygen uptake was not different when walking with the WalkAbout compared with the usual walk. Eight subjects (responders) walked further with the WalkAbout compared to their usual walk (164.90 +/- 55.72 m vs. 140.82 +/- 55.94 m). Seven subjects (non-responders) walked a shorter distance while using the WalkAbout compared to their usual walk (241.79 +/- 73.06 m vs. 281.24 +/- 82.83 m). Compared to non-responders, responders were older, had more severe disability, and were more likely to use an assistive device for walking. Responders walked more slowly, had a shorter stride length, and walked shorter distances in 5 min than non-responders.
Answer: The WalkAbout may help persons with PD who have more severe disability to walk farther. These data could be beneficial in selecting a helpful walking aid for persons with PD.
[A]:
Does evaluation of a new device to prevent fall in persons with Parkinson 's disease?