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.

Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds.", 'We first determined pressure pain thresholds in 25 healthy volunteers (22-31years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60min of non-invasive ventilation-NIV30 and NIV60-(same dyspnoea evaluation).', 'In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of baseline during NIV30 and NIV60 (p<0.05).
Does relieving dyspnoea by non-invasive ventilation decrease pain thresholds in amyotrophic lateral sclerosis?

Beta defensins are secreted from ovine oviduct epithelial cells (OOECs) in response to microbial infection, and are potential alternatives to antibiotic agents in the treatment of microorganism infection, particularly given the abuse of antibiotic agents and the increasing number of drug-resistant bacteria. The aberrant expression of defensins may result in disorders involving organ and oviduct inflammation, such as salpingitis.', 'In the present study, we investigated the effects of LPS on the mRNA expression levels of sheep -defensin-1 (SBD-1) in ovine oviduct epithelial cells. The OOECs in vitro culturing system were established and treated with different concentrations of LPS for indicated time. In addition, MAPK inhibitors and TLR4 antibodies were pretreated to investigate the potential mechanism which involves in LPS regulating SBD-1 expression.', 'LPS markedly upregulated SBD-1 expression in a concentration- and time-dependent manner. Treatment with 100ng/mL LPS resulted in the phosphorylation of JNK, ERK and P38 MAPK. Interestingly, the LPS stimulated SBD-1 expression was attenuated by pretreatment with the P38 MAPK inhibitors SB203580 and SB202190 but not the JNK inhibitor SP600125, while the ERK inhibitor PD98059 had a minor effect. Furthermore, treatment with a Toll-like receptor 4 (TLR4) neutralizing antibody significantly decreased P38 MAPK phosphorylation and LPS induced SBD-1 expression.
Does lipopolysaccharide induce SBD-1 expression via the P38 MAPK signaling pathway in ovine oviduct epithelial cells?

PARP-1 is important for the recognition of both endogenous and exogenous DNA damage, and binds to DNA strand breaks including intermediates of base excision repair (BER). Once DNA-bound, PARP-1 becomes catalytically activated synthesizing PAR polymers onto itself and other repair factors (PARylation). As a result, BER repair proteins such as XRCC1 and DNA polymerase (pol ) are more efficiently and rapidly recruited to sites of DNA damage. In the presence of an inhibitor of PARP activity (PARPi), PARP-1 binds to sites of DNA damage, but PARylation is prevented. BER enzyme recruitment is hindered, but binding of PARP-1 to DNA is stabilized, impeding DNA repair and leading to double-strand DNA breaks (DSB). Deficiencies in pol (-/-) and Xrcc1(-/-) cells resulted in hypersensitivity to the PARP inhibitor 4-AN and reexpression of pol or XRCC1, in these contexts, reversed the 4-AN hypersensitivity phenotype. BER deficiencies also showed evidence of replication defects that lead to DSB-induced apoptosis upon PARPi treatment. Finally, the clinically relevant PARP inhibitors olaparib and veliparib also exhibited hypersensitivity in both pol (-/-) and Xrcc1(-/-) BER-deficient cells. These results reveal heightened sensitivity to PARPi as a function of BER deficiency.
Do base excision repair defects invoke hypersensitivity to PARP inhibition?