Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin,Carbonic Anhydrase IX,and Survivin in Chemically Induced Breast Cancer in Female Rat

Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of βIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of βIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that βIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance.     

Functionalised magnetic microspheres with hydrophilic properties for molecular diagnostic applications

Magnetic microspheres are increasingly attractive for diverse applications in numerous medical and biological areas, such as diagnostics, drug targeting, and biotechnology. Magnetic nonporous hydrophilic microspheres poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate)-(P(HEMA-co-EDMA)), poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate)–(P(HEMA-co-GMA)), and poly(glycidyl methacrylate)– (PGMA) were prepared by single-step dispersion polymerisation in the presence of sterically or electrostatically stabilised colloidal magnetite or maghemite. Several enzymes, such as RNase A, DNase I, proteinase K, and Salmonella antibodies were immobilised on the microspheres and their applicability in degradation of bacterial RNA, chromosomal, and plasmid DNAs, degradation of intracellular PCR inhibitors and immunomagnetic separation of Salmonella cells were demonstrated. Genomic DNA was successfully isolated from cell lysates on weakly acid derivatives of magnetic P(HEMA-co-EDMA) and P(HEMA-co-GMA) microspheres in the presence of PEG 6000 and sodium chloride. Heterogeneous lanthanide complexes of ethylenediaminetetraacetic acid (EDTA) immobilised on insoluble PGMA support were used as catalysts of plasmid DNA cleavage. The effect of components used in the microsphere preparation on PCR course was investigated and PCR application was developed for the testing of the effect of components.     

Direct fabrication of surface relief gratings in chalcogenide glasses by excimer laser interference lithography

In this paper we study the possibility to realise surface relief gratings in thin chalcogenide glass films by holographic exposure using a pulsed KrF excimer laser. Gratings with a period of 540 nm and depths of 100–300 nm were patterned at the surface of 1 μm thick films. Due to coupling of an incident near-infrared laser beam to waveguide modes a resonance-like polarisation dependent decline of transmission was observed at specific incidence angles. Just one laser pulse with a fluence of 12 mJ/cm² per beam was sufficient to achieve the required grating parameters in sulphide glasses with low T _g.     

The Cyclic Cystine Ladder of Theta‐Defensins as a Stable,Bifunctional Scaffold: A Proof‐of‐Concept Study Using the Integrin‐Binding RGD Motif.

Peptides have the specificity and size required to target the protein–protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ‐Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin‐binding Arg‐Gly‐Asp (RGD) motif into the θ‐defensin RTD‐1. The most active analogue had an IC₅₀ of 18 nM for the α_vβ₃ integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ‐defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β‐strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity.     

Wax Ester Analysis of Bats Suffering from White Nose Syndrome in Europe

The composition of wax esters (WE) in the fur of adult greater mouse–eared bats (Myotis myotis), either healthy or suffering from white nose syndrome (WNS) caused by the psychrophilic fungus Pseudogymnoascus destructans, was investigated by high‐resolution mass spectrometry analysis in the positive ion mode. Profiling of lipid classes showed that WE are the most abundant lipid class, followed by cholesterol esters, and other lipid classes, e.g., triacylglycerols and phospholipids. WE abundance in non‐polar lipids was gender‐related, being higher in males than in females; in individuals suffering from WNS, both male and female, it was higher than in healthy counterparts. WE were dominated by species containing 18:1 fatty acids. Fatty alcohols were fully saturated, dominated by species containing 24, 25, or 26 carbon atoms. Two WE species, 18:1/18:0 and 18:1/20:0, were more abundant in healthy bats than in infected ones.     

Red light for red-light cameras?: A meta-analysis of the effects of red-light cameras on crashes

A meta-analysis has been conducted on the effects of red-light cameras (RLCs) on intersection crashes. The size and direction of results reported from studies included in the meta-analysis are strongly affected by study methodology. The studies that have controlled for most confounding factors yield the least favourable results. Based on these studies, installation of RLCs leads to an overall increase in the number of crashes by about 15%. Rear-end collisions increase by about 40% and right angle collisions, which are the target crashes for RLC, are reduced by about 10%. All effects are, however, non-significant. Meta-regression analysis shows that results are more favourable when there is a lack of control for regression to the mean (RTM). An interaction is found between control for RTM and control for those spillover effects that result from the tendency of RLCs to affect crash levels in nearby intersections without RLC. In studies controlling for RTM, additional control for spillover effects reduces the favourability of results still further. Studies controlling for both RTM and spillover effects tend also to control for more additional factors than other studies. It is likely that the results are affected by additional moderator variables, which could not be investigated in this meta-analysis. RLCs may reduce crashes under some conditions, but on the whole RLCs do not seem to be a successful safety measure.     

The effects of electronic stability control (ESC) on crashes--an update

The present study is an update of the meta-analysis by Erke (Erke, A., 2008. Effects of Electronic Stability Control (ESC) on accidents: a review of empirical evidence. Accident Analysis & Prevention, 40 (1), 167–173). Results from 12 studies of the effects of Electronic Stability Control (ESC) on the number of different types of crashes were summarized by means of meta-analysis. The results indicate that ESC prevents about 40% of all crashes involving loss of control. The greatest reductions were found for rollover crashes (−50%), followed by run-off-road (−40%) and single vehicle crashes (−25%). These results are however likely to be somewhat overestimated, especially for non-fatal crashes. Multiple vehicle crashes were found to be largely unchanged. Reductions were found for some types of multiple vehicle crashes. Rear-end collisions are unchanged or may increase. Fatal crashes involving pedestrians, bicycles or animals were found to increase as well. ESC was found to be more effective in preventing fatal crashes than non-fatal crashes. ESC is often found to be more effective in Sports Utility Vehicles (SUVs) than in passenger cars. This may be due to differences between drivers of SUVs and passenger cars. The results from meta-analysis indicate that drivers of ESC-equipped vehicles are likely to be safer drivers than other drivers. All the same, ESC may lead to behavioural adaptation in some cases, but it is not likely that behavioural adaptation offsets the positive safety effects. This may be due to a lack of knowledge about ESC.     

Correlation of Mycobacterium avium subsp. paratuberculosis counts in gastrointestinal tract, muscles of the diaphragm and the masseter of dairy cattle and potential risk for consumers

Tissues of cattle intended for human consumption can be contaminated by Mycobacterium avium subsp. paratuberculosis (MAP). Although different studies attribute varying roles of MAP in Crohn's disease progression it is thought that the exposure of humans to this bacterium should in any case be minimised. In this study, we have collected samples of intestine, mesenteric lymph nodes, muscles of diaphragm (musculus diaphragma) and masseter muscles (musculus masseter) from twenty-five cows in a slaughterhouse. The infectious status of all animals was confirmed by culture of faeces. MAP was found in almost all the intestines and mesenteric lymph nodes examined, including three faecal culture-negative animals indicating intermittent shedding. As intestine is used for the traditional production of sausages, it is alarming that 84.2% of intestine samples were positive for MAP. F57 and IS900 real time PCR revealed MAP in 40 to 68% of diaphragms and 11.1 to 38.9% of masseters. A noticeable dependence of the probability of MAP positivity of faeces versus gastrointestinal tract (GIT) and of GIT and muscles was observed. Due to the changing behaviour of consumers, both of these muscles have started to be widely used in cuisine. Therefore, the results of this paper imply that the processing of cows with paratuberculosis in abattoirs without any precautions (restrictions) and the usage of meat for human consumption should be rethought.