The 3D organization of the mineralized scales of the sturgeon has structures reminiscent of dentin and bone: A FIB-SEM study.

Scales are structures composed of mineralized collagen fibrils embedded in the skin of fish. Here we investigate structures contributing to the bulk of the scale material of the sturgeon (Acipencer guldenstatii) at the millimeter, micrometer and nanometer length scales. Polished and fracture surfaces were prepared in each of the three anatomic planes for imaging with light and electron microscopy, as well as focused ion beam - scanning electron microscopy (FIB-SEM). The scale is composed of three layers, upper and lower layers forming the bulk of the scale, as well as a thin surface layer. FTIR shows that the scale is composed mainly of collagen and carbonated hydroxyapatite. Lacunae are present throughout the structure. Fracture surfaces of all three layers are characterized by large diameter collagen fibril bundles (CFBs) emanating from a plane comprising smaller diameter CFBs orientated in different directions. Fine lineations seen in polished surfaces of both major layers are used to define planes called here the striation planes. FIB-SEM image stacks of the upper and lower layers acquired in planes aligned with the striation planes, show that CFBs are oriented in various directions within the striation plane, with larger CFBs emanating from the striation plane. Fibril bundles oriented in different directions in the same plane is reminiscent of a similar organization in orthodentin. The large collagen fibril bundles emanating out of this plane are analogous to von Korff fibrils found in developing dentin with respect to size and orientation. Scales of the sturgeon are unusual in that their mineralized collagen fibril organization contains structural elements of both dentin and bone. The sturgeon scale may be an example of an early evolved mineralized material which is neither bone nor dentin but contains characteristics of both materials, however, the fossil data required to confirm this is missing.

Three dimensional structures of the inner and outer pig petrous bone using FIB-SEM: Implications for development and ancient DNA preservation.

We report on the 3D ultrastructure of the mineralized petrous bone of mature pig using focused ion beam - scanning electron microscopy (FIB-SEM). We divide the petrous bone into two zones based on the degree of mineralization; one zone close to the otic chamber has higher mineral density than the second zone further away from the otic chamber. The hypermineralization of the petrous bone results in the collagen D-banding being poorly revealed in the lower mineral density zone (LMD), and absent in the high mineral density zone (HMD). We therefore could not use D-banding to decipher the 3D structure of the collagen assembly. Instead we exploited the anisotropy option in the Dragonfly image processing software to visualize the less mineralized collagen fibrils and/or nanopores that surround the more mineralized zones known as tesselles. This approach therefore indirectly tracks the orientations of the collagen fibrils in the matrix itself. We show that the HMD bone has a structure similar to that of woven bone, and the LMD is composed of lamellar bone with a plywood-like structural motif. This agrees with the fact that the bone close to the otic chamber is fetal bone and is not remodeled. The lamellar structure of the bone further away from the otic chamber is consistent with modeling/remodeling. The absence of the less mineralized collagen fibrils and nanopores resulting from the confluence of the mineral tesselles may contribute to shielding DNA during diagenesis. We show that anisotropy evaluation of the less mineralized collagen fibrils could be a useful tool to analyze bone ultrastructures and in particular the directionality of collagen fibril bundles that make up the bone matrix.

Development of Yttrium-Doped BaTiO3 for Next-Generation Multilayer Ceramic Capacitors.

The use of electronic devices that incorporate multilayer ceramic capacitors (MLCCs) is on the rise, requiring materials with good electrical properties and a narrow band gap. This study synthesized yttrium-substituted barium titanate (Ba1-x Y x TiO3, BYT) using a sol-gel process at 950 °C with varying concentrations of yttrium (0 ≤ x ≤ 0.3). X-ray diffraction analysis showed that the tetragonal phase became less pronounced as the yttrium content increased. The samples had varying grain sizes and porosity, with the BY30%T sample having the narrowest band gap at 2.21 eV. The BYT ceramic with 30% yttrium had a thermal conductivity of up to 7 W/m K and an electrical conductivity down to 0.002 (Ω cm)-1 at 180 °C. The current-voltage characteristics of the BYT MLCC were also studied, showing potential use in next-generation high-capacity MLCCs. This work presents BYT as a promising material for these types of capacitors.

Functionality and Activity of Sol-Gel-Prepared Co and Fe co-Doped Lead-Free BTO for Thermo-Optical Applications.

The BTO, BFTC, and BCTF compounds were synthesized by the sol-gel method. The XRD study revealed the formation of single-phase tetragonal perovskite structures with the space group (P4mm). The crystalline parameters were studied as a function of Fe and Co contents and occupation of Ba and/or Ti sites by Fe and Co in the BTO lattice. It was found that the obtained strain increases when Ba2+ is substituted by Co2+ and Ti4+ by Fe3+. The Raman investigation confirmed the existence of three active modes (B1/E (TO1LO), (E (TO)/A1(TO3), and (A 1(LO)/E (TO), all of which are related to the existence of the tetragonal phase and strongly support the XRD results. The microstructural study showed a clear correlation between the presence of Fe and Co and the grain size distribution. Optical studies revealed the improvement in band gap energy with transition-metal (Fe and Co) co-doped BTO ceramics. The decrease in the band gap is explained by the competing effects of Columbian interactions, microdeformation, and oxygen defects. The results indicate that the presence of Fe and Co dopants enhances the absorption in the BTO ceramic. The dopants demonstrated an effect on thermal conductivity: they decreased the thermal conductivity of BTO, which is in the range of 0.76-2.23 W m-1 K-1 at room temperature and 2.02-0.27 W m-1 K-1 at elevated temperatures. The microstructure of the manufactured materials and the grain size distribution affect the compressive strength.

The petrous bone contains high concentrations of osteocytes: One possible reason why ancient DNA is better preserved in this bone.

The characterization of ancient DNA in fossil bones is providing invaluable information on the genetics of past human and other animal populations. These studies have been aided enormously by the discovery that ancient DNA is relatively well preserved in the petrous bone compared to most other bones. The reasons for this better preservation are however not well understood. Here we examine the hypothesis that one reason for better DNA preservation in the petrous bone is that fresh petrous bone contains more DNA than other bones. We therefore determined the concentrations of osteocyte cells occluded inside lacunae within the petrous bone and compared these concentrations to other bones from the domestic pig using high resolution microCT. We show that the concentrations of osteocyte lacunae in the inner layer of the pig petrous bone adjacent to the otic chamber are about three times higher (around 95,000 lacunae per mm3) than in the mastoid of the temporal bone (around 28,000 lacunae per mm3), as well as the cortical bone of the femur (around 27,000 lacunae per mm3). The sizes and shapes of the lacuna in the inner layer of the petrous bone are similar to those in the femur. We also show that the pig petrous bone lacunae do contain osteocytes using a histological stain for DNA. We therefore confirm and significantly expand upon previous observations of osteocytic lacuna concentrations in the petrous bone, supporting the notion that one possible reason for better preservation of ancient DNA in the petrous bone is that this bone initially contains at least three times more DNA than other bones. Thus during diagenesis more DNA is likely to be preserved in the petrous bone compared to other bones.

Application of liposomes in the treatment of infectious diseases.

The advances in the development of drugs and vaccines for major infectious diseases of tuberculosis (TB), malaria and HIV represent some of the most significant milestones in their therapeutic strategies. Yet, current drugs and vaccines display limitations such as drug resistance and low efficacy level. In recent years, new emerging and advanced nano-technology carrier liposomes have been widely studied towards producing drugs and vaccines capable of targeting infectious diseases. Liposomes portrayed biocompatible and biodegradable properties with versatile flexibility, characteristics that are advantageous for a good targeting at the site of action. The success of liposomes has renewed interest in the research and development of liposomal drugs and vaccines shifting the paradigm in infectious diseases treatment. This review focuses on the limitations of current therapeutic drugs and vaccines, the knowledge of liposomes in terms of their classifications and advantages, and a review of the application of liposomes in the treatment of TB, malaria, and HIV infection.

Production, Characterization, and Antimicrobial Activity of Mycocin Produced by Debaryomyces hansenii DSMZ70238.

The present study was conducted to estimate the antimicrobial activity and the potential biological control of the killer toxin produced by D. hansenii DSMZ70238 against several pathogenic microorganisms. In this study, the effects of NaCl, pH, and temperature, killer toxin production, and antimicrobial activity were studied. The results showed that the optimum inhibitory effect of killer toxin was at 8% NaCl, and the diameters of clear zones were 20, 22, 22, 21, 14, and 13 mm for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pyogenes, Candida albicans, and Candida neoformans, respectively. The largest inhibition zones were observed at pH 4.5 with inhibition zone of 16, 18, 17, 18, 11, and 12 mm for the same microorganisms. The results also showed that 25°C is the optimal temperature for toxin killing activity against all targeted microorganisms. In addition, the activity of killer toxin significantly inhibited the growth of fungal mycelia for all target pathogenic fungi and the percentages of inhibition were 47.77, 48.88, 52.22, and 61.11% for Trichophyton rubrum, Alternaria alternata, Trichophyton concentricum, and Curvularia lunata, respectively. The results showed the highest growth rate of D. hansenii DSMZ70238 under condition of 8% NaCl concentration, pH 4.5, and 25°C for 72 h.

Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery.

PURPOSE: To develop a technique to quantify biomechanical changes in the cornea after microkeratome incisions as would be performed in laser in situ keratomileusis. SETTING: St Thomas' Hospital, London, and the Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom. METHODS: Corneal displacements of whole sheep eyes were studied under hydrostatic loading using electronic speckle pattern interferometry before and after microkeratome incisions. RESULTS: After hydrostatic loading, there was a 20.7% increase in corneal displacement in corneas with microkeratome incisions compared to unoperated corneas; this was statistically significant (P=.0068, unpaired t test). CONCLUSIONS: Results show that in the formation of the microkeratome flap, collagen fibers are severed and minimal biomechanical loading is distributed through the flap. Corneal biomechanical integrity is compromised after microkeratome incisions.

Neutralization of infectivity of diverse R5 clinical isolates of human immunodeficiency virus type 1 by gp120-binding 2'F-RNA aptamers.

Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1(Ba-L). These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell.

High affinity nucleic acid aptamers for streptavidin incorporated into bi-specific capture ligands.

We have isolated 2'-Fluoro-substituted RNA aptamers that bind to streptavidin (SA) with an affinity around 7 +/- 1.8 nM, comparable with that of recently described peptide aptamers. Binding to SA was not prevented by prior saturation with biotin, enabling nucleic acid aptamers to form useful ternary complexes. Mutagenesis, secondary structure analysis, ribonuclease footprinting and deletion analysis provided evidence for the essential structural features of SA-binding aptamers. In order to provide a general method for the exploitation of these aptamers, we produced derivatives in which they were fused to the naturally structured RNA elements, CopT or CopA. In parallel, we produced derivatives of CD4-binding aptamers fused to the complementary CopA or CopT elements. When mixed, these two chimeric aptamers rapidly hybridized, by virtue of CopA-CopT complementarity, to form stable, bi-functional aptamers that we called 'adaptamers'. We show that a CD4-SA-binding adaptamer can be used to capture CD4 onto a SA-derivatized surface, illustrating their general utility as indirect affinity ligands.