Phage phi29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase

Protein p56 encoded by the Bacillus subtilis phage 29 inhibits host uracil-DNA glycosylase (UDG) activity. In previous studies, we suggested that this inhibition is likely a defense mechanism developed by phage 29 to prevent the action of UDG if uracilation occurs in DNA either from deamination of cytosine or the incorporation of dUMP during viral DNA replication. In this work, we analyzed the ability of 29 DNA polymerase to insert dUMP into DNA. Primer extension analysis showed that viral DNA polymerase incorporates dU opposite dA with a catalytic efficiency only 2-fold lower than that for dT. Using the 29 DNA amplification system, we found that 29 DNA polymerase is also able to carry out the extension of the dA:dUMP pair and replicate past uracil. Additionally, UDG and apurinic-apyrimidinic endonuclease treatment of viral DNA isolated from 29-infected cells revealed that uracil residues arise in 29 DNA during replication, probably as a result of misincorporation of dUMP by the 29 DNA polymerase. On the other hand, the action of UDG on uracil-containing 29 DNA impaired in vitro viral DNA replication, which was prevented by the presence of protein p56. Furthermore, transfection activity of uracil-containing 29 DNA was significantly higher in cells that constitutively synthesized p56 than in cells lacking this protein. Thus, our data support a model in which protein p56 ensures an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracil residues present in the 29 genome.     

Different patterns of renal osteodystrophy in Iberoamerica

The various forms of renal osteodystrophy are predominant hyperparathyroid bone disease, mixed uremic osteodystrophy, low turnover osteomalacia, and adynamic bone disease. The present study analyses a total number of 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain). Low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. In all centers, independent of the aluminum staining technique used, the extent of aluminum deposited in bone was greater in patients presenting with low bone turnover, whether from low turnover osteomalacia or adynamic bone disease, than in the predominant hyperparathyroid bone disease. In summary, even though recent reports have indicated that, over the last decade, the incidence of aluminum-induced toxicity was reduced, aluminum still seems to be implicated in a great percentage of symptomatic low bone remodelling lesions in Iberoamerica.     

Predictors of hepatitis B surface antigen loss,relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB.     

A low molecular weight OLED material: 2-(4-((2-hydroxyethyl)(methyl)amino)benzylidene)malononitrile. Synthesis,crystal structure,thin film morphology,spectroscopic characterization and DFT calculations

2-(4-((2-Hydroxyethyl)(methyl)amino)benzylidene)malononitrile (HEMABM) was synthesized from 4-[hydroxymethyl(methyl)amino]benzaldehyde and propanedinitrile to obtain a low molecular weight fluorescent material with an efficient solid-state emission and electroluminescence properties comparable to the well-known poly(2-methoxy-5(2′-ethyl)hexoxyphenylenevinylene) (MEH-PPV). The HEMABM was used to prepare an organic light-emitting diode by a solution process. Despite the title compound being a small molecule, it showed optical properties and notable capacity to form a film with smooth morphology (10.81 nm) closer to that of polymer MEH-PPV (10.63 nm). The preparation of the device was by spin coating, the electrical properties such as threshold voltage were about 1.0 V for both HEMABM and MEH-PPV, and the luminance 1300 cd m⁻² for HEMABM and 2600 cd m⁻² for MEH-PPV. This low molecular weight compound was characterized by SCXRD, IR, NMR, and EI. Besides a quantitative analysis of the intermolecular interactions by PIXEL, density functional theory (DFT) calculations are reported.

A low molecular weight fluorescent malononitrile derivative showed an efficient solid-state emission and electroluminescence properties.