Bottom-Up Assembly of Hydrogels from Bacteriophage and Au Nanoparticles: The Effect of Cis- and Trans-Acting Factors

Hydrogels have become a promising research focus because of their potential for biomedical application. Here we explore the long-range, electrostatic interactions by following the effect of trans-acting (pH) and cis-acting factors (peptide mutation) on the formation of Au-phage hydrogels. These bioinorganic hydrogels can be generated from the bottom-up assembly of Au nanoparticles (Au NP) with either native or mutant bacteriophage (phage) through electrostatic interaction of the phage pVIII major capsid proteins (pVIII). The cis-acting factor consists of a peptide extension displayed on the pVIII that mutates the phage. Our results show that pH can dictate the direct-assembly and stability of Au-phage hydrogels in spite of the differences between the native and the mutant pVIII. The first step in characterizing the interactions of Au NP with phage was to generate a molecular model that identified the charge distribution and structure of the native and mutant pVIII. This model indicated that the mutant peptide extension carried a higher positive charge relative to the native pVIII at all pHs. Next, by monitoring the Au-phage interaction by means of optical microscopy, elastic light scattering, fractal dimension analysis as well as Uv-vis and surface plasmon resonance spectroscopy, we show that the positive charge of the mutant peptide extension favors the opposite charge affinity between the phage and Au NP as the pH is decreased. These results show the versatility of this assembly method, where the stability of these hydrogels can be achieved by either adjusting the pH or by changing the composition of the phage pVIII without the need of phage display libraries

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Effectiveness of DNA-recombinant anti-hepatitis B vaccines in blood donors: a cohort study

<p>Abstract</p> <p>Background</p> <p>Although various studies have demonstrated efficacy of DNA-recombinant anti-hepatitis B vaccines, their effectiveness in health care settings has not been researched adequately. This gap is particularly visible for blood donors, a group of significant importance in the reduction of transfusion-transmitted hepatitis B.</p> <p>Methods</p> <p>This is a double cohort study of 1411 repeat blood donors during the period 1998–2002, involving a vaccinated and an unvaccinated cohort, with matching of the two in terms of sex, age and residence. Average follow-up was 3.17 person-years. The outcome measure was infection with hepatitis B virus (HBV), defined by testing positive on serologic markers HBsAg or anti-HBC. All blood donors were from the blood bank in Joaçaba, federal state of Santa Catarina, Brazil.</p> <p>Results</p> <p>The cohorts did not differ significantly regarding sex, age and marital status but the vaccinated cohort had higher mean number of blood donations and higher proportion of those residing in the county capital Joaçaba. Hepatitis B incidences per 1000 person-years were zero among vaccinated and 2,33 among non-vaccinated, resulting in 100% vaccine effectiveness with 95% confidence interval from 30,1% to 100%. The number of vaccinated persons necessary to avoid one HBV infection in blood donors was estimated at 429 with 95% confidence interval from 217 to 21422.</p> <p>Conclusion</p> <p>The results showed very high effectiveness of DNA-recombinant anti-HBV vaccines in blood donors. Its considerable variation in this study is likely due to the limited follow-up and the influence of confounding factors normally balanced out in efficacy clinical trials.</p