NAD(P)H:Quinone Oxidoreductase 1 (NQO1) P187S Polymorphism and Prostate Cancer Risk in Caucasians

NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A “C” to “T” transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1 ⁶⁰⁹TT genotype, and low to intermediate activity was detected in NQO1 ⁶⁰⁹CT genotype compared with ⁶⁰⁹CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy–Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.     

京沪区域创新系统比较研究

在对上海和北京两地高新技术企业调查访谈基础上,对两地区域创新系统的高新技术企业的技术来源、企业合作网络、运行机理、经营成效进行了科学分析。研究表明,与外国公司的合作,对京沪两地高新技术企业开拓新产品市场、理清发展思路具有重要影响;与国内高校、科研机构的合作,对高新技术企业的新技术开发能力建设具有积极意义;上海区域创新系统当前经济效益较好,而北京潜在创新能力较强。     

Protein–Polymer Hybrid Amphiphiles

Biohybrid amphiphiles composed of a protein head group and a hydrophobic polymer tail self‐assemble in water in a similar way as low molecular weight surfactants. Owing to the presence of the protein, biohybrid amphiphiles, and their assemblies, however, hold the additional feature of a built‐in (bio)functionality. These compounds therefore are promising building blocks for the synthesis of functional nanometer‐sized materials. We discuss recent advances in the relatively young field of protein–polymer hybrid amphiphiles, which so far mainly involved exploratory and fundamental studies providing a conceptual basis for the development of more complex systems with interesting applications in the future.

     

Polyethylene and cobalt–chromium molybdenium particles elicit a different immune response in vitro

Periprosthetic osteolysis is a major clinical problem that limits the long-term survival of total joint arthroplasties. Particles of prosthetic material stimulate immune competent cells to release cytokines, which may cause bone loss and loosening of the prosthesis. This study examined the following hypothesis. Polyethylene and titanium particles elicit a different immune response in vitro. To test these hypotheses, we used the human bone marrow cell culture model that we have established and previously used to examine particle associated cytokine release. Ultra high molecular weight polyethylene (UHMW-PE) induced a proliferation of CD14 positive cells (monocytes/macrophages) whereas cobalt chromium molybdenium (CoCrMb) particles demonstrated an increased proliferation of CD66b positive cells (granulocytes). Light and scanning microscopic evaluation revealed that the UHMW-PE particles, which have built large clusters of particles (Ø7, 5 μm), were mainly surrounded by the cells and less phagocytosed. On the other hand the smaller particles from CoCrMb have been phagocytosed by the cells. These results provide strong support for our hypothesis: that wear particles derived from prosthetic materials of different material can elicit significantly different biologic responses. In summary the results suggest that the “in vitro” response to wear particles of different biomaterials should be investigated by culture systems of various lineages of cells.     

A comparison of different nanostructured biomaterials in subcutaneous tissue

The nanostructured surface of a material can improve its interaction with cells and its acceptance as an implant. We compared two novel biomaterials with different nanostructures: Bioverit((R)) II with a coating of nanoporous silica and chitosan-hydroxyapatite composite materials. Pure Bioverit((R)) II served as a control. Platelets of these materials were implanted for 28, 85 and 300 days in the subcutaneous tissue in the neck of 38 rabbits. After excising the specimens they were fixed, embedded in epoxy resin and analyzed histologically. All coated Bioverit((R)) II implants showed a thin capsule of connective tissue. After 300 days, these capsules tended to be thicker than in pure Bioverit((R)) II. No signs of inflammation were observed and the materials appeared unaltered by visual inspection. In case of chitosan-hydroxyapatite composites, massive capsules consisting of dense connective tissue were found, and the material showed signs of biodegradation in form of fissures and cavities. In conclusion, the nanoporous coating showed no obvious positive effect with regard to capsule formation; the chitosan-hydroxyapatite implants provoked a stronger interaction between cells and material. However, most Bioverit((R)) II implants showed no alterations optically, whereas chitosan-hydroxyapatite was partly degraded in all cases.     

Internalization of hydroxyapatite nanoparticles in liver cancer cells

Hydroxyapatite (HAP) is the main inorganic component of hard tissues and shows excellent biocompatibility and osteoconductivity properties. Nanoparticles of HAP can be synthesised by the precipitation method in distilled water. The needle shaped particles are below 100 nm in size with low-crystallinity and high-surfacial activation. Recent studies showed toxic effects of HAP nanoparticles on cancer cells. Other studies focus on the application of HAP nanoparticles as drug and gene delivery system or cell marker. However, to date, the exact internalization pathway of HAP nanoparticles into cells has not been determined. When HAP nanoparticles were added to cell culture medium, the particles immediately became instable and formed agglomerates with a size of about 500–700 nm. Hence, cells seldom encounter single HAP nanoparticles in the environment of cell culture or body fluid. The TEM showed internalized HAP captured by vacuoles in the cytoplasm of the hepatocellular carcinoma cells. The invaginations in the cell membrane before nanoparticle uptake suggested endocytic pathways as internalization mechanism. This study revealed that agglomerated HAP nanoparticles were internalized by cells through the energy-dependent process of clathrin-mediated endocytosis. Depletion of intracellular potassium arrested the formation of coated pit, which inhibited the uptake of HAP.     

Supramolecular porphyrin polymers in solution and at the solid-liquid interface

We have investigated in detail the self-assembly of a chiral porphyrin trimer in different solvents and correlated this behavior to the aggregation of the molecule at a solid-liquid interface. In n-hexane and cyclohexane, CD spectroscopy and dynamic and static light scattering studies showed that the porphyrin trimer self-assembles already at micromolar concentrations into long, chiral supramolecular polymers, which precipitate as fibers when the solution is drop-cast onto a mica surface. In contrast, in chloroform, the compound is molecularly dissolved up to concentrations of 0.2 mM and when micromolar solutions are drop-cast onto mica, no precipitation of large assemblies occurs. Instead, at the moment that the chloroform film becomes subject to spinodal dewetting and the porphyrin trimers within this film start to self-assemble, extended patterns of equidistant lines of single molecule thick columnar stacks are formed.     

Towards an integrated description of hydrogen bonding and dehydration: decreasing false positives in virtual screening with the HYDE scoring function

We developed a new empirical scoring function, HYDE, for the evaluation of protein-ligand complexes. HYDE estimates binding free energy based on two terms for dehydration and hydrogen bonding only. The essential feature of this scoring function is the integrated use of log P-derived atomic increments for the prediction of free dehydration energy and hydrogen bonding energy. Taking the dehydration of atoms within the interface into account shows that some atoms contribute favorably to the overall score, while others contribute unfavorably. For instance, hydrogen bond functions are penalized if they are dehydrated unless they can overcompensate this loss by forming a hydrogen bond with excellent geometry. The main stabilizing contribution represents the removal of apolar groups from the water: the hydrophobic effect. Initial studies using the DUD dataset show that with HYDE, there is a significant decrease in false positives, a reasonable categorization of compounds as either non-binders, weak, medium or strong binders, and in particular, there is a generally applicable and thermodynamically sensible cutoff score below which there is a high likelihood that the compound is indeed a binder.     

New aramid‐based nanocomposites: Synthesis and characterization

New type of nanocomposites containing various proportions of montmorillonite in aromatic polyamide was prepared via solution intercalation method. Aramid chains were synthesized by reacting 4,4′‐oxydianiline with isophthaloyl chloride in N,N′‐dimethyl acetamide. Dodecylamine was used as swelling agent to change the hydrophilic nature of montmorillonite into organophilic. Appropriate amounts of organoclay were mixed in the polymer solution using high‐speed mixer for complete dispersion of the clay. Thin films cast from these materials after evaporating the solvent were characterized by XRD, TEM, mechanical, thermal, and water absorption measurements. The structure and morphology of the nanocomposites determined by XRD and TEM revealed the formation of exfoliated and intercalated clay platelets in the aramid matrix. Mechanical data indicated improvement in the tensile strength and modulus of the nanocomposites with clay loading up to 6 wt%. The glass transition temperature increased up to 12 wt% clay content and thermal stability amplified with increasing clay loading. The water absorption reduced gradually as a function of organoclay and approached to zero with 20 wt% organoclay in the aramid. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers     

Sustainable energy development in Austria until 2020: Insights from applying the integrated model "e3.at"

This paper reports on the Austrian research project "Renewable energy in Austria: Modeling possible development trends until 2020". The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006-2020, using the integrated environment-energy-economy model "e3.at". The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy.