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: Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins.', 'Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography.', 'No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis.
Answer: Our results agree with previous work suggesting that mutations in this gene are not a frequent cause of the frontotemporal dementia phenotype in Canadian patients.

SOLUTION: Are tAU mutations a predominant cause of frontotemporal dementia in Canadian patients?

PROBLEM: Context: Chronic stress is generally known to exacerbate the development of numerous neuropsychiatric diseases such as fear and anxiety disorders, which is at least partially due to the disinhibition of amygdala subsequent to the prolonged stress exposure. GABA receptor A (GABAAR) mediates the primary component of inhibition in brain and its activation produces two forms of inhibition: the phasic and tonic inhibition. While both of them are critically engaged in limiting the activity of amygdala, their roles in the amygdala disinhibition subsequent to chronic stress exposure are largely unknown.', 'We investigated the possible alterations of phasic and tonic GABAAR currents and their roles in the amygdala disinhibition subsequent to chronic stress. We found that both chronic immobilization and unpredictable stress led to long lasting loss of tonic GABAAR currents in the projection neurons of lateral amygdala. By contrast, the phasic GABAAR currents, as measured by the spontaneous inhibitory postsynaptic currents, were virtually unaltered. The loss of tonic inhibition varied with the duration of daily stress and the total days of stress exposure. It was prevented by pretreatment with metyrapone to block corticosterone synthesis or RU 38486, a glucocorticoid receptor antagonist, suggesting the critical involvement of glucocorticoid receptor activation. Moreover, chronic treatment with corticosterone mimicked the effect of chronic stress and reduced the tonic inhibition in lateral amygdala of control mice. The loss of tonic inhibition resulted in the impaired GABAergic gating on neuronal excitability in amygdala, which was prevented by metyrapone pretreatment.
Answer: Our study suggests that enduring loss of tonic but not phasic GABAAR currents critically contributes to the prolonged amygdala disinhibition subsequent to chronic stress. We propose that the preferential loss of tonic inhibition may account for the development of stress-related neuropsychiatric diseases.

SOLUTION: Does chronic stress impair GABAergic control of amygdala through suppressing the tonic GABAA receptor currents?

PROBLEM: Context: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host's soft and hard tissues (e.g., alveolar bone), which could lead to periodontitis.", 'The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model.', 'Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis.
Answer: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.

SOLUTION:
Does porphyromonas gingivalis decrease osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways?