TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: HBV covalently closed circular DNA (cccDNA), the replicative intermediate responsible for persistent HBV infection of hepatocytes, is the template for transcription of all viral mRNAs. Nuclear cccDNA accumulates as a stable episome organized into minichromosomes by histone and nonhistone proteins. In this study we investigated, by a newly developed sensitive and specific assay, the relationship between viral replication and HBV chromatin assembly, transcription, and interaction with viral and cellular regulatory proteins.', 'To achieve this aim we coupled a quantitative chromatin immunoprecipitation (ChIP) technique to an established method that allows the amplification of virion-encapsidated HBV genomes after transfection of linear HBV DNA into human hepatoma HuH7 cells. The cccDNA-ChIP technique was also applied to study HBV minichromosome transcriptional regulation in liver tissue from HBV-infected patients.', 'The use of anti-acetyl-H4/-H3 specific antibodies to immunoprecipitate transcriptionally active chromatin revealed that HBV replication is regulated by the acetylation status of the cccDNA-bound H3/H4 histones. Class I histone deacetylases inhibitors induced an evident increase of both cccDNA-bound acetylated H4 and HBV replication. Finally, histones hypoacetylation and histone deacetylase 1 recruitment onto the cccDNA in liver tissue correlated with low HBV viremia in hepatitis B patients.\Question: Is hepatitis B virus replication regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones?

SOLUTION: We developed a ChIP-based assay to analyze, in vitro and ex vivo, the transcriptional regulation of HBV cccDNA minichromosome. Our results provide new insights on the regulation of HBV replication and identify the enzymatic activities that modulate the acetylation of cccDNA-bound histones as new therapeutic targets for anti-HBV drugs.

PROBLEM: Context: Opioid-induced spastic paraplegia after transient spinal cord ischemia during aortic surgery has been reported. Opioids modulate neurotransmission through mu (μ) opioid receptors (MORs) in the spinal ventral horn. However, their effects during ischemic insult are not understood.', 'The effects of the selective μ agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on ischemia-induced agonal currents were examined in the spinal lamina IX neurons of neonatal rats by using the whole-cell patch-clamp technique. Ischemia was simulated in vitro by oxygen/glucose deprivation.', 'DAMGO (1 μM) produced outward currents in ~60% of spinal lamina IX neurons at a holding potential of -70 mV. Superfusion with ischemia-simulating medium elicited an agonal current. The latency was 457 ± 18 s. Despite its neuromodulatory effects, DAMGO did not significantly change the latencies of the agonal currents with (440 ± 23 s) or without (454 ± 33 s) DAMGO-induced currents.\Question: Does the mu opioid receptor activation affect ischemia-induced agonal currents in rat spinal ventral horn?

SOLUTION: Activation of MORs does not influence ongoing ischemia-induced neuronal death. Our findings indicate that MOR agonist administration should be suitable as an anesthetic during aortic surgery.

PROBLEM: Context: Isovolumic acceleration (IVA) obtained by tissue Doppler echocardiography (TDE) is a sensitive and relatively load-independent index for assessing systolic ventricular function. IVA also has the ability to describe the force-frequency relationship during incremental atrial pacing in vivo.', 'We sought to assess the ability of IVA to detect global left ventricular (LV) dysfunction induced by coronary constriction.', 'In 6 open-chest anesthetized pigs we examined right ventricular and LV long-axis function by TDE (4-chamber view) with simultaneous invasive measurements of intraventricular pressure, maximum dP/dt, minimum dP/dt, and tau by microtip catheter. A pneumatic cuff was placed around the proximal portion of left anterior descending coronary artery (LAD) and distal flow was monitored by transonic flow probe. Mean arterial pressures were monitored by indwelling cannula. Baseline studies assessed force-frequency relationships with TDE and invasive measurements during incremental pacing from 100 to 200/min (20/min increments every 10 minutes). The protocol was repeated 10 minutes after balloon inflation to reduce LAD blood flow by 50%.', 'Compared with baseline, LV pressure decreased significantly (P = .03, 2-way analysis of variance) as did maximum dP/dt (P < .004) with LAD constriction. At the same time IVA and isovolumic velocity at the LV free wall were significantly reduced (P < .002 and P = .04, respectively) and both IVA and isovolumic velocity were correlated with dP/dt (r = 0.45, P < .002, and r = 0.35, P < .02, respectively). TDE systolic indices were unchanged in the right ventricle.\Question: Do isovolumic but not ejection phase Doppler tissue indices detect left ventricular dysfunction caused by coronary stenosis?

SOLUTION:
IVA detects changes in global LV systolic function during LAD constriction and may be a useful clinical tool to diagnose ischemia.