TASK DEFINITION: Given a passage, 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: To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.', 'Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.', 'The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor alpha could stimulate the expression of CCL13 in synovial fibroblasts; IL-1beta was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.

SOLUTION: Does induction of CCL13 expression in synovial fibroblasts highlight a significant role of oncostatin M in rheumatoid arthritis?

PROBLEM: Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters.', 'In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations.', 'First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo.

SOLUTION: Is there no transmural heterogeneity in an index of action potential duration in the canine left ventricle?

PROBLEM: Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development.', 'Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe.', 'Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in the caudal raphe.

SOLUTION:
Do peptidergic agonists of activity-dependent neurotrophic factor protect against prenatal alcohol-induced neural tube defects and serotonin neuron loss?