Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma

The lack of advanced animal models of human cancers is considered a barrier to developing effective therapeutics. Canine and human melanomas are histologically disparate but show similar disease progression and response to therapies. The purpose of these studies was to compare human and canine melanoma tumours and cell lines regarding MAPK and PI3K/AKT signalling dysregulation, and response to select molecularly targeted agents. Pathway activation was investigated via microarray and mutational analysis. Growth inhibition and cell cycle effects were assessed for pathway inhibitors AZD6244 (MAPK) and rapamycin (PI3K/AKT) in human and canine melanoma cells. Human and canine melanoma share similar differential gene expression patterns within the MAPK and PI3K/AKT pathways. Constitutive pathway activation and similar sensitivity to AZD6244 and rapamycin was observed in human and canine cells. These results show that human and canine melanoma share activation and sensitivity to inhibition of cancer‐related signalling pathways despite differences in activating mutations.     

Health and growth performance of the blue mussel (Mytilus edulis L.) from two hanging cultivation sites in the German Bight: a nearshore—offshore comparison

The health of cultivated blue mussels from an offshore and a nearshore sites was compared by assessing lysosomal membrane stability (LMS) and accumulations of lipofuscin and neutral lipids in the digestive glands. In addition, the condition index, parasite infestation rates, growth performance and energy status of the mussels were assessed during 10?months of sampling. Abiotic and biotic site characteristics were investigated by water analysis for each sampling cycle. Further, data of contaminant loads of the softbody and pollutant concentration of the water column, suspended particles and sediments from both sites were analysed. Results show that positive offshore effects due to dilution of contamination were not evident for all parameters analysed. Condition indices were high, and parasites were not present in offshore mussels. In contrast, the integrative health parameter LMS and growth performance were slightly, but not significantly, better in the nearshore cultivated mussels. These findings correspond with the higher contaminant concentrations in the softbodies of mussels and the water column from the offshore testing site. Both sites showed low LMS values and high accumulations of lipofuscin and neutral lipids, indicating that environmental conditions in the German Bight are generating stress for blue mussels even in the offshore areas. Exposure to fluvial transport points to a comparable probability for high contamination loads similar to nearshore areas. We therefore recommend adding a minimum salinity threshold to the definition of offshore aquaculture to exclude areas under fluvial influence.     

MUSSEL CULTIVATION AS A CO-USE IN OFFSHORE WIND FARMS: POTENTIAL AND ECONOMIC FEASIBILITY

More than 50% of the annual worldwide harvest of mussels is produced in Europe. The mussel cultivation in Germany is based on an extensive on-bottom culture and depends entirely on natural resources for food, spat and space. Due to stakeholder conflicts and a lack of spat availability, mussel farmers tend to move offshore where space is not limited and adequate settlement guaranteed. Newcomers – the offshore wind farmers – are covering large areas in the German Bight which in contrast give the opportunity to use these areas in a multifunctional way by accepting mussel cultivation within the wind farms. This study compiles the basic data for offshore mussel cultivation in close vicinity to a designated offshore wind farm in the open sea of the German Bight and employs different case-scenario calculations to illustrate the impact of changing parameter values on overall profitability or non-profitability of this activity. Primary focus is placed on the production of consumer mussels but seed mussel cultivation is also taken into consideration. We show that production of consumer mussels with longline technology is sufficiently profitable even under the assumption of substantial cost increases. This is especially true, if existing capacities could be used. The cultivation of seed mussels depends on the possibility of using existing equipment. A substantial increase of seed mussel prices to at least 0.6 €, given the main cost categories remaining constant, turns this alternative into substantial profitability. This study concludes with providing some recommendations on how favorable terms or actions could further improve profitability of offshore mussel cultivation. Altogether, our results are intended to shed some light on business management topics that future offshore mariculture operators such as traditional mussel farmers should follow in order to be efficient.     

The control of sclerotinia stem rot on oilseed rape (Brassica napus): current practices and future opportunities

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorum is a major disease of oilseed rape (Brassica napus). During infection, large, white/grey lesions form on the stems of the host plant, perturbing seed development and decreasing yield. Due to its ability to produce long‐term storage structures called sclerotia, S. sclerotiorum inoculum can persist for long periods in the soil. Current SSR control relies heavily on cultural practices and fungicide treatments. Cultural control practices aim to reduce the number of sclerotia in the soil or create conditions that are unfavourable for disease development. These methods of control are under increased pressure in some regions, as rotations tighten and inoculum levels increase. Despite their ability to efficiently kill S. sclerotiorum, preventative fungicides remain an expensive gamble for SSR control, as their effectiveness is highly dependent on the ability to predict the establishment of microscopic infections in the crop. Failure to correctly time fungicide applications can result in a substantial cost to the grower. This review describes the scientific literature pertaining to current SSR control practices. Furthermore, it details recent advances in alternative SSR control methods including the generation of resistant varieties through genetic modification and traditional breeding, and biocontrol. The review concludes with a future directive for SSR control on oilseed rape.     

Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine

Myocardial and pancreatic lesions induced by sublethal doses of T-2 toxin in swine were characterized by light and electron microscopy. Toxin was given intravenously to six 17- to 18-week-old pigs. Pigs were killed 24 or 48 hours after treatment. Grossly, subendocardial hemorrhages, multifocal pinpoint white foci in myocardium, and pancreatic edema occurred in one treated pig. Histologic changes in myocardium of treated pigs consisted of multifocal edema, mononuclear cell infiltration, myofiber hyalinization, vacuolation, and contraction bands with nuclear pyknosis. Ultrastructurally, there were areas of edema, myofibrillar disorganization, dilation of sarcoplasmic reticulum, and formation of hypercontraction bands. Myocardial mineralization was seen in the pig with gross lesions. Pancreatic changes in treated pigs consisted of multifocal acinar degeneration and necrosis. Ultrastructural changes included irregular dilation of rough endoplasmic reticulum and abnormal zymogen granules. Thus, in addition to radiomimetic lesions of the gastrointestinal tract and lymphoid organs, heart and pancreas are target organs of T-2 toxin in swine.     

Gas chromatographic analysis of milk for deoxynivalenol and its metabolite DOM-1

A gas chromatographic method is described for the determination of deoxynivalenol (DON) and its metabolite DOM-1 in milk. Milk samples were extracted with ethyl acetate on a commercially available disposable extraction column, followed by hexane-acetonitrile partitioning. Final purification was accomplished on a reverse phase C-18 cartridge. The trimethylsilyl ether (TMS) derivatives of DON were prepared, chromatographed on an OV-17 column, and quantitated with an electron capture detector. Chromatography of the TMS derivatives of milk extracts was compared to that of the corresponding heptafluorobutyryl derivatives. The limit of detection using TMS derivatives was 1 ng/mL for both toxins with recoveries averaging 82% +/- 9% at 2.5 and 10 ng/mL milk for DON and 85% +/- 6% at 10 ng/mL for DOM-1.     

Inconspicuous Nutrient Laden Surface Runoff from Mature Forest Sierran Watersheds

It is generally held that surface runoff in heavily forested ecosystems is minimal and therefore nutrient fluxes via runoff are unimportant. This is based in large measure on the absence of direct observation or remnant physical evidence. It is further held that protected forests with heavy understory and litter serve as a nutrient sink due to maximum uptake and interception. Our Sierran studies have detected the presence of surface runoff at several sites in the form of both overland and litter interflow with concentrations of NH₄-N as high as 87.2 mg L^?1, NO₃-N as high as 95.4 mg L^?1, and PO₄-P as high as 24.4 mg L^?1. Data suggest that nutrients are derived from the mature O-horizons, and that there has been little contact with the mineral soil or root zone where strong retention and/or uptake of these ions would be expected. Such contributions from overland/interflow could be particularly important in areas where ultra-oligotrophic lakes (e.g., Lake Tahoe) are now trending towards meso-oligotrophic status. We believe that fire exclusion in these systems may have exacerbated N and P inputs to Lake Tahoe and elsewhere by allowing unnatural buildups of O-horizons that are apparently a source of nutrients to surface runoff.     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)