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.     

Treatment of rupture of suspensory ligament and superficial flexor tendon in a bull

Rupture of the suspensory ligament at the insertions on the proximal sesamoid bones, and of the superficial flexor tendon of the left fore limb, occurred in an adult Angus bull as a result of fighting. There was severe hyperextension of the metacarpophalangeal (MCP) joint with the dewclaws almost touching the ground. Radiographs revealed severe hyper-extension of the MCP joint with the sesamoid bones aligned directly distal to the metacarpus. Initially, a full length fiberglass cast was applied with the limb partially flexed within the cast and the heels elevated. The cast was replaced twice. The cast was removed after 136 days and the bull was bearing full weight on the limb. Prolonged immobilisation of the limb produced new bone in the area (a normal response in cattle) to cause ankylosis of the traumatized MCP joint and partial ankylosis of the carpus. The bull was being used for pasture breeding one year after the injury.     

Mechanical comparison of materials used for extra-capsular stabilisation of the stifle joint in dogs

Objective The mechanical properties of three materials (No. 2 polypropylene, No. 5 polybutilate-coated multifilament polyester and 18, 27 and 36 kg test monofilament nylon leader material) commonly used for extra-capsular stabilisation of the stifle in dogs with cranial cruciate ligament insufficiency were determined. The ability of No. 5 polybutilate-coated multifilament polyester and 36 kg test monofilament nylon leader material, when placed as extra-capsular sutures, to mitigate cranial drawer was evaluated in hindlimbs of cadavers. Design An in vitro mechanical study. Animals Seven pairs of hindlimbs harvested from adult greyhound dogs recently euthanased for other reasons. Procedure Samples of each material, including samples of 27 kg test leader material that had been sterilised by one of three methods (ethylene oxide, one or five cycles in an autoclave), were loaded to determine tensile and stress relaxation properties. The effect of cyclic loading on a No. 5 polybutilate-coated multifilament polyester and 36 kg test leader material was also determined. Using the harvested hindlimbs, cranial drawer was measured before and after transection of the cranial cruciate ligament and on the first and twelfth cycle following extra-capsular stabilisation with either No. 5 polybu-tilate-coated multifilament suture or 36 kg test leader material. Results Leader material was found to have the most suitable mechanical characteristics for use as extracapsular stabilisation of the cranial cruciate ligament deficient stifle. Of the sterilisation methods, ethylene oxide was found to have the least detrimental effects on the handling and material characteristics of the leader material. Stifles stabilised with 36 kg test leader material had significantly less drawer than those stabilised with No. 5 polybutilate-coated multifilament polyester suture. Clinical implications Monofilament nylon leader material would appear to have suitable mechanical properties for extra-capsular stabilisation of the cranial cruciate ligament deficient stifle. If possible the material should be sterilised using ethylene oxide.     

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.     

Pliocene paleoclimate and East antarctic ice-sheet history from surficial ash deposits

The preservation, age, and stratigraphic relation of an in situ ashfall layer with an underlying desert pavement in Arena Valley, southern Victoria Land, indicate that a cold-desert climate has persisted in Arena Valley during the past 4.3 million years. These data indicate that the present East Antarctic Ice Sheet has endured for this time and that average temperatures during the Pliocene in Arena Valley were no greater than 3 degrees C above present values. One implication is that the collapse of the East Antarctic Ice Sheet due to greenhouse warming is unlikely, even if global atmospheric temperatures rise to levels last experienced during mid-Pliocene times.     

Radioactive elements on Mercury's surface from MESSENGER: implications for the planet's formation and evolution

The MESSENGER Gamma-Ray Spectrometer measured the average surface abundances of the radioactive elements potassium (K, 1150 ± 220 parts per million), thorium (Th, 220 ± 60 parts per billion), and uranium (U, 90 ± 20 parts per billion) in Mercury's northern hemisphere. The abundance of the moderately volatile element K, relative to Th and U, is inconsistent with physical models for the formation of Mercury requiring extreme heating of the planet or its precursor materials, and supports formation from volatile-containing material comparable to chondritic meteorites. Abundances of K, Th, and U indicate that internal heat production has declined substantially since Mercury's formation, consistent with widespread volcanism shortly after the end of late heavy bombardment 3.8 billion years ago and limited, isolated volcanic activity since.     

A long-snouted predatory dinosaur from africa and the evolution of spinosaurids

Fossils discovered in Lower Cretaceous (Aptian) rocks in the Tenere Desert of central Niger provide new information about spinosaurids, a peculiar group of piscivorous theropod dinosaurs. The remains, which represent a new genus and species, reveal the extreme elongation and transverse compression of the spinosaurid snout. The postcranial bones include blade-shaped vertebral spines that form a low sail over the hips. Phylogenetic analysis suggests that the enlarged thumb claw and robust forelimb evolved during the Jurassic, before the elongated snout and other fish-eating adaptations in the skull. The close phylogenetic relationship between the new African spinosaurid and Baryonyx from Europe provides evidence of dispersal across the Tethys seaway during the Early Cretaceous.