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.

Q: 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?

A: 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.
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Q: Context: Hypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction.', "Apolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as meanSEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey's post hoc test.", 'Creatinine clearance (L/min) was similar between C57 (17117) and ApoE (14026) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (1128, ~-35%, p<0.05) and ApoE (6110, ~-56%, p<0.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 737; OVX: 738, p<0.05) when compared to C57 animals (Sham: 493; OVX: 604), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.15.7; OVX: 33.74.7) and ApoE sham animals (26.43.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.65.8, p<0.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.20.4; C57 OVX: 22.91.0; ApoE Sham: 13.90.7; ApoE OVX: 34.01.4 au x 103, p<0.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 00; C57 OVX: 00; ApoE Sham: 6.81.6; ApoE OVX: 5.20.8% x 10-2, p<0.05). Ovariectomy resulted in a similar reduction in ER- protein expression in the renal cortex (C57: 0.780.04; ApoE: 0.810.04 au, p<0.05) when compared to sham animals (C57:1.000.04; ApoE: 1.030.03 au).\Question: Do endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice?

A: Taken together these data indicate that female sex hormones may delay hypercholesterolemia-induced renal dysfunction and emphasizes the importance of plasma cholesterol control in post-menopausal women.
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Q: Context: This study compared the pharmacokinetics of a single dose of 1% testosterone solution after application to the inner arm or the axilla as application sites for transdermal testosterone therapy.', 'Healthy, not pregnant, premenopausal women, 18 to 45 years of age with a body mass index of 20 to 28 kg/m(2) were enrolled into a single-center, open-label, randomized, 2-way crossover study. Serum total testosterone (TT), free testosterone (fT), and sex hormone binding globulin concentrations were measured. Pharmacokinetic parameters determined from serum TT and fT included area under the serum concentration versus time curve from time zero (pre-dose) until 72 hours post-dose (AUC0-72), Cmax, and Tmax. Descriptive statistics were performed on serum concentrations of TT and fT for each site. ANOVA was performed on AUC0-72 and Cmax.', 'A single-dose application of 1% testosterone solution to the inner arm and the axilla produced clear increases in TT and fT. Slower and lower increases in TT and fT were observed after treatment to the inner arm. Based on baseline-corrected AUC versus time curves, the bioavailability of 1% testosterone solution was increased 2-fold for the axilla compared with the inner arm.\Question: Does application site affect the pharmacokinetics of topical testosterone applied to the axilla compared with the inner arm?

A:
The absorption of a 1% testosterone solution was significantly greater after application to the axilla than to the inner arm. Study number DDS16; Australian Therapeutic Goods Administration, CTN 2005/158.
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