Estrogenic effect of propylparaben (propylhydroxybenzoate) in rainbow trout Oncorhynchus mykiss after exposure via food and water

The estrogenic effect of propylparaben was investigated in a rainbow trout Oncorhynchus mykiss test system. Propylparaben was administered orally to sexually immature rainbow trout every second day for up to 10 days in doses between 7 and 1830 mg kg(-1) 2 d(-1) and in the water at 50 and 225 microg l(-1) for 12 days. Plasma vitellogenin was measured before and during the exposures and the concentrations of propylparaben in liver and muscle were determined at the end of experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 33 mg propylparabenkg(-1) 2 d(-1); the most sensitive fish responded to 7 mg kg(-1). The ED(50) values for increase in vitellogenin synthesis were 35, 31 and 22 mg kg(-1) 2 d(-1) at day 3, 6 and 11, respectively. Exposure to 225 microg propylparabenl(-1) increased vitellogenin synthesis, but exposure to 50 microg l(-1) did not. Propylparaben showed little tendency to bioaccumulation in rainbow trout; less than 1 per thousand of the total amount of propylparaben administered orally at 1830 mg kg(-1) 2 d(-1) over the 10-d experimental period was retained in muscle and liver 24 h after the end of the experiment. Exposure to 225 microg propylparabenl(-1) for 12 d led to concentrations of 6700 and 870 microg propylparabenkg(-1) liver and muscle, respectively. Half lives for propylparaben were 8.6 h in liver and 1.5 h in muscle.     

Distribution, standing stock, growth, mortality and production of Strongylocentrotus pallidus (Echinodermata: Echinoidea) in the northern Barents Sea

The regular sea urchin, Strongylocentrotus pallidus (G.O. Sars, 1871), is a widespread epibenthic species in high-Arctic waters. However, little is known about its distribution, standing stock, population dynamics and production. In the northern Barents Sea, S. pallidus was recorded on seabed still photographs at 10 out of 11 stations in water depths of 80–360?m. Mean abundances along photographic transects of 150–300 m length ranged between <0.1 and 14.7?ind. m^?2 yielding a grand average of 3.6?ind.?m^?2. The small-scale distribution along the transects was patchy, with densities varying from nil to an overall maximum of 25.5 ind. m^?2, and exhibited a significant relation to the number of stones present. Sea urchin test diameters, measured on scaled photographs, extended from 7 to 90?mm. Median values at single stations varied from 14 to 46?mm, showing a significant inverse relationship to water depth. Biomass, estimated by combining photographic abundances, size frequencies and a size-mass function established with trawled specimens, ranged between <0.1 and 3.0?g ash-free dry mass m^?2, averaging about 1.0?g ash free dry mass m^?2. An analysis of skeletal growth bands in genital plates was carried out with 143 trawled individuals ranging in test diameter (D) from 4 to 48?mm. Assuming these bands to represent annual growth marks, the ages of the specimens analysed ranged between 3 and 42 years. A von Bertalanffy function was fitted to size-at-age data to model individual growth pattern (D_∞?=?102.3?mm, k?=?0.011 year^?1, t₀?=?0.633?year). The annual mortality rate Z of the population in the northern Barents Sea was estimated from a size-converted catch curve to be 0.08 year^?1. Applying the weight-specific growth rate method, the average P/B ratio and the mean annual production of this population were estimated as 0.07 year^?1 and 0.076?g AFDM m^?2 year^?1, respectively. In conclusion, S. pallidus is characterized by slow growth, low mortality, high longevity and low productivity. Because of its relatively high biomass, it is considered to contribute significantly to total benthic standing stock and carbon flux in the study area.     

Ceramide acyl chain length markedly influences miscibility with palmitoyl sphingomyelin in bilayer membranes

Ceramides are precursors of major sphingolipids and can be important cellular effectors. The biological effects of ceramides have been suggested to stem from their biophysical effects on membrane structure affecting the lateral and transbilayer organization of other membrane components. In this study we investigated the effect of acyl chain composition in ceramides (C4-C24:1) on their miscibility with N-palmitoyl-sphingomyelin (PSM) using differential scanning calorimetry. We found that short-chain (C4 and C8) ceramides induced phase separation and lowered the T _m and enthalpy of the PSM endotherm. We conclude that short-chain ceramides were more miscible in the fluid-phase than in the gel-phase PSM bilayers. Long-chain ceramides induced apparent heterogeneity in the bilayers. The main PSM endotherm decreased in cooperativity and enthalpy with increasing ceramide concentration. New ceramide-enriched components could be seen in the thermograms at all ceramide concentrations above X _Cer = 0.05. These broad components had higher T _m values than pure PSM. C24:1 ceramide exhibited complex behavior in the PSM bilayers. The miscibility of C24:1 ceramide with PSM at low (X _Cer = 0.05–0.10) concentrations was exceptionally good according to the cooperativity of the transition. At higher concentrations, multiple components were detected, which might have arisen from interdigitated gel-phases formed by this very asymmetric ceramide. The results of this study indicate that short-chain and long-chain ceramides have very different effects on the sphingomyelin bilayers. There also seems to be a correlation between their miscibility in binary systems and the effect of ceramides of different hydrophobic length on sphingomyelin-rich domains in multicomponent membranes.     

Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR

Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory tract leading to condylomas and respiratory papillomatosis. HPV infections are restricted to epithelial tissue and the progression through the virus lifecycle is tightly coordinated to the differentiation of the host cell. The changes of cellular microRNAs by HPV-11 gene expression were investigated in a cell culture model of HaCaT cells transfected with HPV-11, with the goal of understanding which cellular processes were affected by the virus. Human microRNA profiling was conducted on three different array platform systems and because very few microRNAs (miR-663, -638, -149* and -92b*) were consistently found in all three array data sets we performed extensive statistical analyses of the array data and the qRT-PCR validation. We assume that the most reliable differentially expressed microRNAs are the ones identified by more than one array platform. We also show that TaqMan? qRT-PCR validation is of limited use for less abundant microRNAs.     

Manual pressure distension of the human saphenous vein changes its biomechanical properties-implication for coronary artery bypass grafting

Patency rates of saphenous vein grafts following coronary artery bypass grafting (CABG) depend on multiple factors. Information regarding the impact of biomechanical properties of vein grafts on patency rates is not available. The objective of the present study was to evaluate whether uncontrolled manual pressure distension during routine preparation of the saphenous vein in CABG-induced changes in the biomechanical properties of the vein. The morphometric and stress-strain properties were studied in isolated segments of the saphenous vein from 12 patients undergoing elective CABG. Six segments were manually distended without pressure control and six were not distended. The mechanical test was performed as a ramp inflation using syringe pump. The vein dimensions were obtained from digitised images at different pressures as well as at the no-load and zero-stress states. The circumferences, the wall and lumen area, the wall thickness, and the outer diameter as function of the applied pressure were largest in the segments with uncontrolled manual distension compared to those without distension (P<0.05). The opening angle and the absolute value of the residual strains were lower (P<0.01) and the circumferential stress-strain curve shifted to the left, indicating the wall became stiffer with uncontrolled manual distension compared to those without distension (P<0.05). In conclusion, manual pressure distension changed the morphometric and biomechanical properties of the saphenous vein. The perspective is that studies on biomechanical properties on the saphenous vein may guide surgeons how to handle graft material without causing major changes of the biomechanical properties during harvesting and preparation.     

Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping

Decapping is a key step in mRNA turnover. However, the composition and regulation of the human decapping complex is poorly understood. Here, we identify three proteins that exist in complex with the decapping enzyme subunits hDcp2 and hDcp1: hEdc3, Rck/p54, and a protein in decapping we name Hedls. Hedls is important in decapping because it enhances the activity of the catalytic hDcp2 subunit and promotes complex formation between hDcp2 and hDcp1. Specific decapping factors interact with the mRNA decay activators hUpf1 and TTP, and TTP enhances decapping of a target AU-rich element (ARE) RNA in vitro. Each decapping protein localizes in cytoplasmic processing bodies (PBs), and overexpression of Hedls produces aberrant PBs and concomitant accumulation of a deadenylated ARE-mediated mRNA decay intermediate. These observations suggest that multiple proteins involved in human decapping are important subunits of PBs and are activated on ARE-mRNAs by the protein TTP.     

EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828

To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo.