Nanotoxicology: a personal perspective

Nanoparticles arise from a wide variety of natural and man-made sources and have a diverse array of biological, chemical, and physical properties. The toxicity of these particles can be roughly divided into two categories: 1) the enhanced delivery of toxic agents 2) toxicity induced the properties of the particle itself. The use of nanoparticles to provide enhanced delivery of chemotherapeutics is presented followed by a discussion of the size-based effects of electron transfer and physical membrane disruption. Copyright © 2009 John Wiley & Sons, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63042/1/27_ftp.pd

Importance of thermophilous habitats for protection of wild bees (Apiformes)

Research on wild bees (Apiformes) was conducted in the Lower Oder Valley (NW Poland) at Natura 2000 sites near the border between Poland and Germany. The analysis involved 3 landscape types with xerothermic and sandy grasslands, differing in the proportion of woody vegetation. In total, we collected there 4158 specimens of Apiformes, representing 180 species. We have proved that mid-forest grasslands with a high proportion of thermophilous broad-leaved forests and xerothermic shrub communities are equally attractive to wild bees as open habitats (sandy grasslands, xerothermic grasslands/heaths). We observed varied responses of wild bee species with specific functional characteristics to increasing proportion of woody vegetation. The grasslands surrounded by forests were characterized by the highest number of cleptoparasitic species. In contrast, solitary and social bee species preferred forest-steppe habitats. However, in open habitats, solitary bees were the most abundant. Moreover, open habitats were distinguished by the highest number and abundance of rare species. Active protection of thermophilous grasslands is crucial for biodiversity conservation, also with respect to the natural resources of Apiformes. Preservation of biodiversity in threatened xerothermic and sandy grasslands should be one of the key objectives of nature conservation in European countries. Currently, more and more actions are undertaken to improve their condition and to restore those particularly valuable and threatened habitat types

Quantification of cytosolic plasmid DNA degradation using high‐throughput sequencing: implications for gene delivery

Background Although cytosolic DNA degradation plays an important role in decreasing transgene expression, the plasmid degradation pattern remains largely unexplored. Methods Illumina dye sequencing was employed to provide degradation site information for S1 and cytosolic nucleases. S1 nuclease provided a positive control for a comparison between the agarose gel method and sequencing approaches. Results The poly(A) region between the β‐lactamase gene and the cytomegalovirus (CMV) promoter was identified as the most likely cut site for polyplex‐treated cytosol. The second most likely site, at the 5' end of the β‐lactamase gene, was identified by gel electrophoresis and sequencing. Additional sites were detected in the OriC region, the SV40/poly(A) region, the luciferase gene and the CMV promoter. Sequence analysis of plasmid treated with cytosol from control cells showed the greatest cut activity in the OriC region, the β‐lactamase gene and the poly(A) region following the luciferase gene. Additional regions of cut activity include the SV40 promoter and the β‐lactamase poly(A) termination sequence. Both cytosolic nucleases and the S1 nuclease showed substantial activity at the bacterial origin of replication ( OriC ). Conclusions High‐throughput plasmid sequencing revealed regions of the luciferase plasmid DNA sequence that are sensitive to cytosolic nuclease degradation. This provides new targets for improving plasmid and/or polymer design to optimize the likelihood of protein expression. Copyright © 2014 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106947/1/jgm2761.pd

Meat quality traits and fatty acid composition of breast muscles from ducks fed with yellow lupin

Abstract The protein sources in feed have a huge impact on good-quality and -quantity meat traits. Yellow lupin (YL) seeds have a similar level of protein as soybean meal (SBM). The most popular is SBM that is genetically modified (GMO). During this age, the consumer market requires non-GMO products. Yellow lupin used as a high-protein substitute for SBM in feed has an effect on the quality of meat from broiler ducks. The aim of the study was to analyse and compare meat quality traits in breast and leg muscles as well as fatty acid (FA) composition in breast muscles from ducks fed mixtures containing YL as an alternative to SBM. Two hundred 1-day-old Cherry Valley ducks were kept in pens on litter in two equal dietary groups, four replications with 25 birds per group. The control group (1) received balanced feed containing SBM. The treatment group (2) received balanced feed containing YL. The feed provided to both groups contained 55% of concentrate and 45% of wheat. Birds received feed and water ad libitum and were reared for 8 weeks. After that, 16 ducks (eight from each group) of BW close to the mean for the whole group were slaughtered. Plucked and gutted carcasses were analysed in a laboratory for quality parameters. Meat was analysed for pH, colour, water-holding capacity and drip loss. Samples of breast muscles were analysed for the content of cholesterol, collagen, intramuscular fat and FA composition. The proposed feed mixture containing YL had no impact on meat traits, content of muscles or fat in duck carcasses (P > 0.05). The values of lightness (L*) and yellowness (b*) and collagen content in breast muscles were significantly higher (P < 0.05) in group 2 (YL). A lower ability to retain water, that is, higher water-holding capacity (percentage of water lost from meat) (P < 0.05), was found for leg muscles from group 2 (YL). The content of C16:0, C18:0, C20:4 n-6, C22:4 n-6, C22:5 n-3, total content of saturated fatty acids (SFA), values of atherogenic index and thrombogenic index were significantly lower (P < 0.05) in group 2 (YL) than in group 1 (SBM). The content of C18:2 n-6 and the polyunsaturated fatty acids-to-SFA ratio (P/S) were significantly higher (P < 0.05) in ducks fed the diet with the inclusion of YL. Diets with YL could be proposed as a partial substitute for SBM in duck-rearing

Origin of broad polydispersion in functionalized dendrimers and its effects on cancer cell binding affinity

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depends exponentially upon the mean number of attached ligands. These two findings are explained with a model in which ligands conjugate to the nanoparticle with a positive cooperativity of $\approx 4kT$, and that nanoparticles bound to a surface by multiple bonds are permanently affixed. This drives new analysis of the data, which confirms that there is only one time constant for desorption, that of a nanoparticle bound to the surface by a single bond.Comment: 4 pages, with 6 figure

Nanoscale Morphology of Type I Collagen is Altered in the Brtl Mouse Model of Osteogenesis Imperfecta

Bone has a complex hierarchical structure that has evolved to serve structural and metabolic roles in the body. Due to the complexity of bone structure and the number of diseases which affect the ultrastructural constituents of bone, it is important to develop quantitative methods to assess bone nanoscale properties. Autosomal dominant Osteogenesis Imperfecta results predominantly from glycine substitutions (80%) and splice site mutations (20%) in the genes encoding the α1 or α2 chains of Type I collagen. Genotype-phenotype correlations using over 830 collagen mutations have revealed that lethal mutations are located in regions crucial for collagen-ligand binding in the matrix. However, few of these correlations have been extended to collagen structure in bone. Here, an atomic force microscopy-based approach was used to image and quantitatively analyze the Dperiodic spacing of Type I collagen fibrils in femora from heterozygous (Brtl/+) mice (α1(I)G349C), compared to wild type (WT) littermates. This disease system has a well-defined change in the col1α1 allele, leading to a well characterized alteration in collagen protein structure, which are directly related to altered Type I collagen nanoscale morphology, as measured by the Dperiodic spacing. In Brtl/+ bone, the D-periodic spacing shows significantly greater variability on average and along the length of the bone compared to WT, although the average spacing was unchanged. Brtl/+ bone also had a significant difference in the population distribution of collagen D-period spacings. These changes may be due to the mutant collagen structure, or to the heterogeneity of collagen monomers in the Brtl/+ matrix. These observations at the nanoscale level provide insight into the structural basis for changes present in bone composition, geometry and mechanical integrity in Brtl/+ bones. Further studies are necessary to link these morphological observations to nanoscale mechanical integrity

Distribution of Type I Collagen Morphologies in Bone: Relation to Estrogen Depletion

Bone is an amazing material evolved by nature to elegantly balance structural and metabolic needs in the body. Bone health is an integral part of overall health, but our lack of understanding of the ultrastructure of healthy bone precludes us from knowing how disease may impact nanoscale properties in this biological material. Here, we show that quantitative assessments of a distribution of Type I collagen fibril morphologies can be made using atomic force microscopy (AFM). We demonstrate that normal bone contains a distribution of collagen fibril morphologies and that changes in this distribution can be directly related to disease state. Specifically, by monitoring changes in the collagen fibril distribution of sham-operated and estrogen-depleted sheep, we have shown the ability to detect estrogen-deficiency-induced changes in Type I collagen in bone. This discovery provides new insight into the ultrastructure of bone as a tissue and the role of material structure in bone disease. The observation offers the possibility of a much-needed in vitro procedure to complement the current methods used to diagnose osteoporosis and other bone disease

Type I Collagen Exists as a Distribution of Nanoscale Morphologies in Teeth, Bones and Tendons

This study demonstrates that collagen, the most abundant protein in animals, exists as a distribution of nanoscale morphologies in teeth, bones, and tendons. This fundamental characteristic of Type I collagen has not previously been reported and provides a new understanding of the nanoscale architecture of this ubiquitous and important biological nanomaterial. Dentin, bone, and tendon tissue samples were chosen for their differences in cellular origin and function, as well as to compare mineralized tissues with a tissue that lacks mineral in a normal physiological setting. A distribution of morphologies was present in all three tissues, confirming that this characteristic is fundamental to Type I collagen regardless of the presence of mineral, cellular origin of the collagen (osteoblast versus odontoblast versus fibroblast), anatomical location, or mechanical function of the tissue

The Croatian Health Survey – Patient\u27s Satisfaction with Medical Service in Primary Health Care in Croatia

The aim of the study was to investigate patient satisfaction with nurses and general practice organization in Croatia. A total of 2,252 patients 18 years of age and over from 47 randomly selected general practices were included in the study. 72.1% of patients were satisfied with nurses and general practice organization. Older and less educated patients were generally more satisfied. Patients were more pleased with nurses’ behavior (81.9%) than with practice organization (62.3%). Factor analysis revealed two underlying discriminates of patient satisfaction – »positive attitude towards the nurse« and »inaccessibility of practice«. The former discriminate emphasized a great potential of nursing, which should be taken into consideration in the transformation of health care system in Croatia

The role of second-neighbor effects in photoemission: Are silicon surfaces and interfaces special?

A widely used assignment scheme for Si 2p2p core-level photoemission studies of silicon oxidation relies solely on the formal oxidation state of the silicon. The tacit assumption of this assignment methodology is that second-neighbor effects have no measurable effect on observed Si 2p2p binding energies. In this letter, new experiments are combined with literature precedents to make the case that the second-neighbor effects play an important role in determining binding energy shifts. © 1998 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70944/2/APPLAB-72-1-46-1.pd