Phosphotyrosine enrichment identifies focal adhesion kinase and other tyrosine kinases for targeting in canine hemangiosarcoma

Canine hemangiosarcoma (HSA) is an endothelial cell malignancy driven, in part, by activating mutations in receptor and non-receptor tyrosine kinases. Proteomics, Western blots and a tyrosine kinase inhibitor were used to elucidate activating mechanisms in HSA cell lines. Phosphotyrosine peptides from focal adhesion kinase (FAK) STAT3, Lyn, Fyn and other signal transduction kinases were identified by mass spectrometry. FAK was constitutively activated at tyrosine 397, the autophosphorylation site, and this was reversible with high concentrations of a FAK inhibitor. FAK inhibitor-14 suppressed migration and phosphorylation of FAK tyrosine 397 and tyrosines 576/577 and was cytotoxic to HSA cells suggesting FAK signalling may be an important contributor to canine HSA survival.     

Studies on the effect of different cyclohexane-1,3-diones on de-novo fatty acid biosynthesis in poaceae

Cyclohexane-1,3-diones such as the herbicides cycloxydim, sethoxydim, alloxydim and clethodim are known to be specific inhibitors of the plastid-located acetyl-CoA carboxylase (ACCase) in Poaceae, a key enzyme of de-novo fatty acid biosynthesis in higher plants. Using several new cyclohexane-1,3-dione derivatives and known herbicides, the relationships between chemical structure and enzyme inhibition have been studied. The basic cyclohexane-1,3-dione structure was modified at three different positions. These compounds were tested for inhibition of the de novo fatty-acid biosynthesis in test systems of etioplasts isolated from Avena sativa L. and Hordeum vulgare L. seedlings and also for inhibition of the isolated barley ACCase. The I₅₀ values of these cyclohexane-1,3-diones were determined. The influence of the modification of alkyl chains (length and type of substituent) on the degree of ACCase-inhibition is discussed. Several new compounds were found that were about two orders more active than the known herbicides cycloxydim or sethoxydim in the etioplast and ACCase test systems but not necessarily on the level of whole plants.     

Estuarine eutrophication in the UK: current incidence and future trends

• 1. Increased inputs of nutrients to estuaries can lead to undesirable effects associated with eutrophication, including algal blooms, changes in species composition and bottom anoxia. Several estuaries and coastal areas around the UK have increased nitrogen (N) and phosphorus (P) concentrations, elevated concentrations of chlorophyll a and changes in algal community composition and abundance. This paper reviews the pressures that lead to high nutrient concentrations in estuaries and considers the likely effectiveness of current and proposed regulatory actions.
• 2. The main sources of nutrients to estuaries are river runoff, sewage discharges, atmospheric inputs and possibly submarine groundwater discharges, although little is known about the latter. Significant reductions in N and P inputs have been realized following application of the EU's Urban Waste Water Treatment Directive. Atmospheric NO_x and NH_x emissions have also decreased and are expected to decrease further in the next decade as implementation of existing legislation continues, and new controls are introduced for activities such as shipping.
• 3. Agricultural inputs reach estuaries principally through diffuse sources, either in surface water (and in some areas possibly groundwater) or, for N, via the atmosphere. Over 10 years ago the Nitrates Directive was introduced to tackle the problem of N discharges from agriculture but little change in N loads to estuaries has been recorded.
• 4. To meet the aims of the EU Water Framework Directive, for at least ‘good’ ecological status, more rigorous application and implementation of the Nitrates Directive, together with changes in the Common Agriculture Policy and farming practice are likely to be needed. Even then, the slow response of the natural environment to change and the inherent variability of estuaries means that their responses may not be as predicted. Research is needed into the relationship between policy drivers and environmental responses to ensure actions taken will achieve the planned results.

Copyright © 2008 John Wiley & Sons, Ltd.     

Size and Geographical Variation in PM1, PM2.5 and PM10: Source Profiles from Soils in the Western United States

Source profiles (fractional mass abundances and uncertainties) for use in chemical mass balance (CMB) source apportionment are reported for soil dust from unpaved roads and desert lands. The objectives were to add to the library of source composition profiles available for CMB studies, and to provide data on the variation in wind-blown dust composition between particle sizes and geographical locations. Samples were resuspended and sampled through PM₁, PM_2.5 and PM₁₀ inlets onto filters, then chemically analyzed for 40 elements, seven ions and eight carbon fractions. Air quality management would benefit from technology that can distinguish soil dust from sites in different geographical locations and sites with different land uses. Five geographical clusters representing Ft Bliss, TX, Dona Ana County, NM, Ft Irwin, CA, the west desert and the Canyonlands, UT, were examined. Distinctive differences were found between sites within a cluster and these differences were comparable to the differences between cluster averages. Some sites showed small differences in chemical composition between particle sizes, but these differences were less than the differences observed between nearby geographical locations. Dust emissions from sites with uniform geology have distinctive source profiles that may be useful for CMB receptor modeling. Heterogeneous regions, defined by land management boundaries, will require extensive field sampling to develop representative composite source profiles.     

A SACRAL LESION RESEMBLING OSTEOCHONDROSIS IN THE GERMAN SHEPHERD DOG

More than 30% (21 of 65) of German Shepherd dogs with clinical signs of cauda equina compression had radiographic and pathologic abnormalities compatible with osteochondrosis of the sacral endplate. Most of these dogs had a defect in the dorsal part of the sacral endplate and a detached bone fragment in the vertebral canal. Similar lesions were also found in growing and young adult dogs without clinical signs. The dogs with clinical signs of cauda equina compression also had severe degenerative disc disease with protrusion of the lumbosacral disc and compression of the cauda equina, suggesting that the signs of cauda equina compression more likely were related to the secondary degenerative changes (disc protrusions) rather than the primary disease. Clinically normal German Shepherds with sacral osteochondrosis usually were younger than 18 months, the dogs with cauda equina compression and sacral osteochondrosis older than 18 months (mean age 4.8 years). On the average, these dogs were two years younger as compared to dogs with cauda equina compression without sacral osteochondrosis. Male dogs are more often affected than females (5:1). There is a breed predisposition: in dogs other than German Shepherds, osteochondrosis of the sacral endplate seems to be extremely rare.     

Pattern recognition and feature extraction of canine celiac and cranial mesenteric arterial waveforms: normal versus chronic enteropathy--a pilot study

In this pilot study, we hypothesize that waveform patterns of the celiac and cranial mesenteric arteries differ pre- and post-prandially in normal dogs compared to those with chronic enteropathy. We further suggest that it is possible to classify these findings according to the type of disease present. Eleven dogs with chronic enteropathy and eight normal dogs were examined. Doppler examinations were performed at times 0 (fasted), and at 20, 40, 60 and 90 min post-prandially. The waveform shapes were described and the following features were extracted: resistive and pulsatility index, mean maximum velocity, mean diastolic velocity, peak systolic velocity, early diastolic notch ratio and the deceleration time interval. Dogs with inflammatory bowel disease had either lower or absent flow at fasting in early diastole compared to the other groups. Resistive and pulsatility indices decreased during digestion in all groups except those with protein losing enteropathy. The increase in mean diastolic flow during digestion in affected dogs was either lacking (protein-losing enteropathy) or significantly lower (inflammatory bowel disease, P<0.05) compared to normal dogs. Dogs with chronic enteropathies had abnormal arterial waveform shapes and suboptimal increases in diastolic blood flow during digestion and these findings worsened with the severity of the histological lesions present. Doppler ultrasound of the celiac and mesenteric arteries has great potential to enhance our understanding of intestinal disease in conscious dogs.     

Paradoxical vestibular disease with trigeminal nerve-sheath tumor in a dog

A thirteen-year old spayed female poodle was referred because of atrophy of temporal and masseter muscles on the left and head tilt and episodical circling to the right side. Additionally, decreased facial sensation, absent menace reaction, palpebral and corneal reflexes on the left side, as well as ipsilateral hemiparesis and tongue palsy were noticed. Generalised vestibular ataxia and hypermetria in the front limbs were present. Based on the clinical signs, the presumptive anatomical localization of the lesion was the cerebellopontine angle including parts of the caudal brainstem with involvement of the trigeminal, facial and hypoglossal nerves. Involvement of either flocculonodular lobe or the caudal cerebellar peduncle on the left side causing paradoxical vestibular disease was suspected. On magnetic resonance imaging a large enhancing lesion in the area of the left cerebellopontine angle involving the trigeminal nerve and compressing cerebellum and brainstem was seen. Because of the poor prognosis the dog was euthanized on the owner's request. This space occupying lesion could be identified as a trigeminal neurofibrosarcoma/schwannoma on post mortem histopathological examination.