We used carbon and nitrogen isotopes to investigate changes in the diet of California condors from the Pleistocene to the recent. During the Pleistocene, condors from California fed on both terrestrial megafauna and marine mammals. Early accounts reported condors feeding on the carcasses of marine mammals, but by the late 1700s, condor diets had shifted predominantly to terrestrial animals, following the commercial harvesting of marine mammals and the development of cattle ranching on land. At present, dairy calves provided by humans significantly augment condor diet, constituting an artificial support of the current population. Reestablishing a marine mammal component in the condor diet may be an effective strategy for fostering viable condor populations independent of direct human subsidies.carbon isotopes ͉ nitrogen isotopes ͉ paleodiet D uring the Pleistocene, California condors (Gymnogyps californianus) ranged from the Pacific coast of North America across the southern U.S. to Florida and north to western New York (1, 2). Historical records show that by the 17th century, condors were restricted to the west coast of North America, from Baja California to British Columbia (3, 4). At present, small reintroduced populations live in California, Arizona, and Baja California. Paleontological evidence suggests that populations of these obligate scavengers were associated with the carcasses of large animals (1). After the late Pleistocene extinction of most large terrestrial mammals in North America (5), condors appear to have been restricted to the west coast, where stranded marine mammals offered the only remaining abundant source of large animal carcasses (1).There is little direct evidence that marine mammals were a significant component of condor diets, however, beyond scattered historical observations. In 1806, Lewis and Clark observed condors feeding on whales near the mouth of the Columbia River (6). Captain Clark wrote on February 16, 1806: ''This bird fly's very clumsily, nor do I know whether it ever seizes it's prey alive, but am induced to believe it does not. We have seen it feeding on the remains of the whale and other fish which have been thrown up by the waves on the sea coast. These I believe constitute their principal food, but I have no doubt but that they also feed on flesh.'' In 1855, Taylor found hundreds of condors feeding on sea lion carcasses on the California coast (7). He wrote: ''During the early part of the present month, large quantities of sea lions have been killed on the southern coast for the oil; the carcasses of these animals on the beach may be seen at times surrounded by hundreds of the Condors. A friend of ours informed us that he saw a few days ago, as many as three hundred of these creatures near such feeding ground, within a distance of a league.'' (7). In the 1860s, Cooper reported on condors feeding on seal and whale carcasses in California, although he never directly observed them doing so (8).To investigate changes in condor diets, we determined the stable carbon ( 12 C...

The endangered California Condor (Gymnogyps californianus) was reduced to a total population of 22 birds by the end of 1982. Their captive-bred descendants are now being released back into the wild in California, Arizona, and Baja California, where monitoring indicates they may accumulate lead to toxic levels. Fragments of ammunition in the carcasses of game animals such as deer, elk, and feral pigs not retrieved by hunters or in gut piles left in the field have been considered a plausible source of the lead, though little direct evidence is available to support this hypothesis. Here, we measured lead concentrations and isotope ratios in blood from 18 condors living in the wild in central California, in 8 pre-release birds, and in diet and ammunition samples to determine the importance of ammunition as a source of exposure. Blood lead levels in pre-release condors were low (average 27.7 ng/mL, SD 4.9 ng/mL) and isotopically similar to dietary and background environmental lead in California. In contrast, blood lead levels in free-flying condors were substantially higher (average 246 ng/mL, SD 229 ng/mL) with lead isotopic compositions that approached or matched those of the lead ammunition. A two-endmember mixing model defined by the background 207Pb/206Pb ratio of representative condor diet samples (0.8346) and the upper 207Pb/206Pb ratio of the ammunition samples (0.8184) was able to account for the blood lead isotopic compositions in 20 out of the 26 live condors sampled in this study (i.e., 77%). Finally, lead in tissues and in a serially sampled growing feather recovered post-mortem from a lead-poisoned condor in Arizona evidence acute exposure from an isotopically distinct lead source. Together, these data indicate that incidental ingestion of ammunition in carcasses of animals killed by hunters is the principal source of elevated lead exposure that threatens the recovery in the wild of this endangered species.

Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by in situ hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells in vitro and in a mouse xenograft model. When tumor cells were cultured in vitro, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer. IMPORTANCEThe natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of freeranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in unaffected raccoons. Unlike other oncogenic polyomaviruses, RacPyV was episomal, not integrated, in these tumors. To determine the stability of the viral genome and sustained transcription of the oncogenic tumor antigen genes, we cultured primary raccoon tumor cells and passaged them in mice, confirming the nonintegrated state of the virus and the maintenance of viral gene transcription throughout. RacPyV provides a naturally occurring and tractable model for a novel mechanism of polyomavirus-mediated oncogenesis.

Pathologic features of 12 cats with naturally acquired systemic hypertension and concomitant hypertensive encephalopathy were analyzed. All cats demonstrated acute onset of signs localized to the forebrain and/or brainstem, including stupor, coma, and seizures. All cats had systemic hypertension, ranging from 160 to 300 mm Hg. Gross lesions were identified in 4 of 12 cases, including caudal herniation of the cerebrum and cerebellum, sometimes with compression of the rostral colliculus and medulla. Histologically, all cases featured bilaterally symmetrical edema of the cerebral white matter. Associated vascular lesions, especially arteriolar hyalinosis, were also observed. Concurrent lesions were chronic tubulointerstitial nephritis (11/12 cases), adenomatous hyperplasia of the thyroid gland (4 cases), hypertensive choroidal arteriopathy (6 cases), and left ventricular hypertrophy (5 cases). This study demonstrates that the typical histologic manifestation of spontaneous hypertensive encephalopathy in cats is bilaterally symmetrical edema of the subcortical cerebral white matter.

The concerted actions of the CNS and the immune system are essential to coordinate the outcome of neuroinflammatory responses. Yet, the precise mechanisms involved in this crosstalk and their contribution to the pathophysiology of neuroinflammatory diseases largely elude us. Here, we show that the CNS-endogenous hedgehog pathway, a signal triggered as part of the host response during the inflammatory phase of multiple sclerosis and experimental autoimmune encephalomyelitis, attenuates the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines. Using a murine genetic model in which the hedgehog signaling is compromised in CD4 T cells, we show that the hedgehog pathway acts on CD4 T cells to suppress pathogenic hallmarks of autoimmune neuroinflammation, including demyelination and axonal damage, and thus mitigates the development of experimental autoimmune encephalomyelitis. Impairment of hedgehog signaling in CD4 T cells exacerbates brain-brainstem-cerebellum inflammation and leads to the development of atypical disease. Moreover, we present evidence that hedgehog signaling regulates the pathogenic profile of CD4 T cells by limiting their production of inflammatory cytokines GM-CSF and IFN-γ and by antagonizing their inflammatory program at the transcriptome level. Likewise, hedgehog signaling attenuates the inflammatory phenotype of human CD4 memory T cells. From a therapeutic point of view, our study underlines the potential of harnessing the hedgehog pathway to counteract ongoing excessive CNS inflammation as systemic administration of a hedgehog agonist after disease onset effectively halts disease progression and significantly reduces neuroinflammation and the underlying neuropathology. We thus unveil a previously unrecognized role for the hedgehog pathway in regulating pathogenic inflammation within the CNS, but also propose to exploit its ability to modulate this neuroimmune network as a strategy to limit the progression of ongoing neuroinflammation.

Olfactory neuroblastoma (ONB) is a rare intranasal neoplasm in both dogs and humans. Similar clinical presentation and overlapping histologic and immunohistochemical features of ONB with other intranasal neoplasms can make diagnosis and treatment of intranasal neoplasia challenging. Furthermore, in part because of their rarity, there is a lack of reporting on therapeutic regimen for these neoplasms. In humans, initial debulking surgery is usually followed by radiation therapy. Here we report on the histologic, immunohistochemical, and ultrastructural characteristics of canine ONB and report on the clinical progression of cases treated with radiation therapy. In all nine canine ONB examined here, neoplastic cells were arranged in a lobular manner amidst a prominent neurofibrillary matrix and had features consistent with Grade III (high grade) ONB. The neoplastic cells demonstrated positive immunohistochemical staining for TuJ-1, a Class III beta-tubulin neuronal cytoskeletal protein, and variable staining for other markers, including chromogranin, synaptophysin,

Meloxicam (2.0 mg/kg, IM, q 12 h for 14 days) did not cause substantial alterations in function of or histopathologic findings for the kidneys of Japanese quail but did induce muscle necrosis; repeated IM administration of meloxicam to quail may be contraindicated.

Canine gastrointestinal sarcomas, a group of tumours that includes leiomyosarcomas (LMSAs), gastrointestinal stromal tumours (GISTs) and other rarer sarcomas, comprise about 10–30% of all gastrointestinal tumours. This study aims to characterize the histologic characteristics and clinical behaviour in order to identify prognostic factors predictive of outcome. A single institution database search for surgically treated gastrointestinal sarcomas yielded 47 cases with adequate tissue remaining for histologic analysis and 42 cases available for analysis of clinical outcome. Tumours were then prospectively evaluated for mitotic count, necrosis, haemorrhage and inflammation, as well as categorized via immunohistochemical (IHC) staining for smooth muscle actin, c‐KIT and DOG‐1. IHC analysis defined 32 tumours as GISTs, 14 as LMSAs and one as a sarcoma not otherwise specified. For both GISTs and LMSAs, the overall median survival time (MST) is 1024 days (range 31–1456), which did not differ statistically between tumour types (p = .92). The overall metastatic rate of GISTs in this study was 32.1% (n = 9) which was not significantly different to that of LMSAs at 15.3% (n = 2, p = .45). In multivariate analysis, mitotic count under 9 in GIST patients and complete surgical excision in all tumour types correlated with improved MST. For patients with GISTs, the intensity of c‐KIT staining also correlated positively with survival, with an MST of 250 days in cases with weak staining and an MST of 1418 days in cases with moderate or strong c‐KIT staining (p = .005).