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Abstract Background Highly fecund mouse strains provide an ideal model to understand the factors affecting maternal performance. The QSi5 inbred strain of mice was selected for high fecundity and low inter-litter interval, and is very successful at weaning large numbers of offspring when compared to other inbred strains. Results Post-natal pup weight gain was used to estimate mammary gland output and to compare the performance of QSi5 mice to CBA mice. Cumulative litter weights and individual pup weight gain was significantly higher throughout the first eight days of lactation in QSi5 mice compared to CBA mice. Morphometric analysis of mammary glands during pregnancy in QSi5 mice revealed a 150 percent greater ductal side branching compared to CBA mice (P < 0.001). Ontology and pathway classification of transcript profiles from the two strains identified an enrichment of genes involved in a number of pathways, including the MAPK, tight junction, insulin signalling and Wnt signalling. Eleven of these genes, including six genes from the MAPK signalling pathway, were identified as associated with postnatal growth. Further, positive mediators of Wnt signalling, including Wnt4, Csnk2a1 and Smad4, were over-represented in the QSi5 strain profile, while negative regulators, including Dkkl1, Ppp2r1a and Nlk, were under-represented. These findings are consistent with the role of Wnt and MAPK signalling pathway in ductal morphogenesis and lobuloalveolar development suggesting enhanced activity in QSi5 mice. A similar pattern of phenotype concordance was seen amongst 12 genes from the tight junction pathway, but a pattern did not emerge from the insulin signalling genes. Amongst a group of differentially expressed imprinted genes, two maternal imprinted genes that suppress growth induced via the IGF signalling pathway, Grb10 and Igf2r, were under-represented in QSi5 mice. Whereas Peg3 and Plagl1, both paternally imprinted genes that enhance neonatal growth, were over-represented in QSi5 mice. Conclusion We propose that the combined action of at least three major signalling pathways involved in mammary gland development and milk secretion, namely Wnt, MAPK and tight junction pathways, contribute to the superior maternal performance phenotype in QSi5 mice. Additionally, favourable expression patterns of the imprinted genes Peg3, Plagl1, Grb10 and Igf2r may also contribute.

Although educators believe that undergraduate internship programmes are a vital component of professional degrees, evidence of the relationship between students' experiences of learning during such programmes and the quality of new graduates' experiences of professional practice is limited. This research sought to investigate associations between veterinary students' experiences of "clinic-based learning" (CBL) during a final year internship programme and their experiences of "veterinary professional practice" (VPP) in the year following graduation. Phenomenographic analysis of semi-structured interview transcripts identified the qualitative variation present in final year interns' conceptions of and approaches to CBL (n = 41). Quantitative statistics were used to explore relationships amongst the quality of these components of students' experiences of learning and performance during the internship programme. Additional quantitative analysis was used to link new graduates' conceptions of and approaches to VPP with their experiences of CBL as final year students (n = 22). This illuminated crucial aspects of students' learning experiences associated with the extent of their transitions to independent practice as entry level veterinarians. The results have implications for the design and teaching of undergraduate internships in a range of professions.

New graduate veterinarians report differing experiences of the transition to practice. Some make a rapid transition to professional autonomy while others require prolonged and extensive support from their colleagues. Factors contributing to this variation are unclear. This study used phenomenography to analyse the conceptions of and approaches to "veterinary professional practice" (VPP) reported by new graduates in semi-structured interviews (n = 22). Quantitative statistical analysis was used to investigate links between the quality of graduates' experiences and their achievement during a comprehensive final year internship programme. Strong associations were identified between the quality of graduates' conceptions of and approaches to VPP. Links were also established between the quality of graduates' conceptions of VPP and their performance in practice prior to graduation. The outcomes of this research can be used to improve teaching and assessment during final year internships and enhance graduate attribute statements for professional degree programmes. The results also indicate that student learning research methodologies can be used to evaluate the quality of graduates' experiences in the workplace. This has implications for career outcomes research in a range of healthcare professions.

This study investigated veterinary students' experiences of clinic-based learning (CBL) during a comprehensive final year internship programme. Open-ended surveys (n = 93) were used to gather qualitative data about students' conceptions of what is learned during CBL and their approaches to learning in clinics. Phenomenography was used for detailed analysis of the variation evident in students' responses. Relationships between qualitative differences in students' conceptions and approaches were then evaluated using quantitative statistical analysis. Links to achievement during final year were examined. Close associations were found between the quality of students' experiences of CBL and achievement during the internship programme. (Contains 4 tables and 3 figures.)

Over three decades ago, Parker and Snow (Am J Physiol 223: 888-893, 1972) demonstrated that canine erythrocytes undergo an increase in cation permeability when incubated with extracellular ATP. In this study we examined the expression and function of the channel/pore-forming [P2X.sub.7] receptor on canine erythrocytes. [P2X.sub.7] receptors were detected on canine erythrocytes by immunocytochemistry and immunoblotting. Extracellular ATP induced [sup.86][Rb.sup.+] ([K.sup.+]) efflux from canine erythrocytes that was 20 times greater than that from human erythrocytes. The [P2X.sub.7] agonist 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-trisphosphate (BzATP) was more potent than ATP, and both stimulated [sup.86][Rb.sup.+] efflux from erythrocytes in a dose-dependent fashion with E[C.sub.50] values of ~7 and ~309 [micro]M, respectively. 2-Methylthioadenosine 5'-triphosphate and adenosine 5'-O-(3-thiotriphosphate) induced a smaller [sup.86][Rb.sup.+] efflux from erythrocytes, whereas ADP, AMP, UTP, or adenosine had no effect. ATP-induced [sup.86][Rb.sup.+] efflux from erythrocytes was inhibited by oxidized ATP, KN-62, and Brilliant blue G, known [P2X.sub.7] antagonists. ATP also induced uptake of [choline.sup.+] into canine erythrocytes that was 60 times greater than that into human erythrocytes. Overnight incubation of canine erythrocytes with ATP and BzATP induced phosphatidylserine exposure in >80% of cells and caused up to 20% hemolysis. In contrast, purinergic receptor; P2Z receptor; extracellular adenosine 5'-triphosphate; red blood cell; dog

The transplantation of beta-glucuronidase expressing neural progenitors into the newborn mice cerebral ventricles reveals that the donor cells are engrafted all over the neuraxis. The various regions of the brain possessed donor-derived cells that are present as normal constituents. The entire neuraxis exhibited the beta-glucuronidase activity.

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Please cite this paper as: Murine epidermal Langerhans cells and keratinocytes express functional P2X7 receptors. Experimental Dermatology 2010; 19: e151-e157. Abstract: Extracellular ATP via the activation of purinergic P2 receptors has an emerging role in cutaneous biology; however, the distribution of these receptors in mouse skin is poorly defined. This study investigated whether murine epidermal cell subpopulations express functional purinergic P2X7 receptors. P2X7 expression was examined by immunoblotting and immunofluorescence staining of epidermal cells from C57Bl/6 mice. P2X7 function was evaluated by nucleotide-induced ethidium+ uptake measurements in epidermal cells from C57Bl/6 mice, and from P2X7 deficient mice and wild-type littermate controls. P2X7 was detected in whole epidermal cell preparations, and specifically on Langerhans cells (LCs) and keratinocytes (KCs). ATP induced ethidium+ uptake into LCs and KCs, with EC50 values of 503 and 482 μ m, respectively. BzATP, and to a lesser extent ATPγS and ADP, also induced ethidium+ uptake; while UTP, αβ-meth-ATP and NAD were ineffective. ATP-induced ethidium+ uptake was impaired by Na+ and Mg2+, and the P2X7 antagonist, A-438079 and was absent in LCs and KCs from P2X7 deficient mice. These results demonstrate that murine LCs and KCs express functional P2X7, and support a role for this receptor in cutaneous biology. [ABSTRACT FROM AUTHOR]

Over three decades ago, Parker and Snow (Am J Physiol 223: 888-893, 1972) demonstrated that canine erythrocytes undergo an increase in cation permeability when incubated with extracellular ATP. In this study we examined the expression and function of the channel/pore-forming P2X7 receptor on canine erythrocytes. P2X7 receptors were detected on canine erythrocytes by immunocytochemistry and immunoblotting. Extra- cellular ATP induced 86Rb+ (K+) efflux from canine erythrocytes that was 20 times greater than that from human erythrocytes. The P2X7 agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine 5′-trisphosphate (BzATP) was more potent than ATP, and both stimulated 86Rb+ efflux from erythrocytes in a dose-dependent fashion with EC50 values of ∼7 and ∼309 μM. respectively. 2-Methylthioadenosine 5′-triphosphate and adenosine 5′-O-(3-thiotriphosphate) induced a smaller 86Rb+ efflux from erythrocytes, whereas ADP, AMP, UTP, or adenosine had no effect. ATP-induced 86Rb+ efflux from erythrocytes was inhibited by oxidized ATP, KN-62, and Brilliant blue G, known P2X7 antagonists. ATP also induced uptake of choline+ into canine erythrocytes that was 60 times greater than that into human erythrocytes. Overnight incubation of canine erythrocytes with ATP and BzATP induced phosphatidylserine exposure in >80% of cells and caused up to 20% hemolysis. In contrast, <30% of human erythrocytes showed phosphatidylserine exposure after overnight incubation with ATP and BzATP, and hemolysis was negligible. Flow cytometric measurements of ATP-induced ethidium+ uptake showed that P2X7 function was three times lower in canine monocytes than in human monocytes. These data show that the massive cation permeability increase induced by extracellular ATP in canine erythrocytes results from activation and opening of the P2X7 receptor channel/pore. [ABSTRACT FROM AUTHOR]

Objective--To characterize the clinical signs of globoid cell leukodystrophy (GLD) in Australian Kelpies from a working line (AWKs) and determine whether an association existed between these signs and degrees of demyelination and inflammatory responses in affected brains. Design--Case-control study. Animals-4 AWKs with GLD (cases) and 7 unaffected young adult dogs of mixed breeding (controls). Procedures-Clinical records were reviewed for information on signalment, and samples of neurologic tissues underwent histological processing, immunohistochemical staining, and image analysis. Findings were compared between case and control dogs. Results--The 4 affected AWKs had progressive ataxia, tremors, and paresis and low leukocyte activity of galactosylceramidase, the lysosomal enzyme deficient in GLD. Image analysis of neurologic tissue revealed globoid cells characteristic of GLD and substantial demyelination in the peripheral and central nervous systems, relative to that in neurologic tissue from control dogs. This was accompanied by microglial activation, reactive astrocytosis, and axonal spheroid formation. Conclusions and Clinical Relevance--The demyelination, inflammatory responses, and axonal spheroids evident in the AWKs were consistent with the clinical signs of peripheral nerve, spinal cord, and cerebellar dysfunction. Because GLD is an autosomal recessive inherited disease, with considerable overlap in galactosylceramidase activity existing among heterozygotes and noncarriers, development of a molecular test is important for preventing the perpetuation of this disease in the Australian Kelpie breed. [ABSTRACT FROM AUTHOR]

Cells of the immune system undergo activation and subsequent proliferation in the normal course of an immune response. Infrequently, the molecular and cellular events that underlie the mechanisms of proliferation are dysregulated and may lead to oncogenesis, leading to tumor formation. The most common forms of immunological cancers are lymphomas, which in dogs account for 8%-20% of all cancers, affecting up to 1.2% of the dog population. Key genes involved in negatively regulating proliferation of lymphocytes include a group classified as tumor suppressor genes (TSGs). These genes are also known to be associated with progression of lymphoma in humans, mice, and dogs and are potential candidates for pathological grading and diagnosis. The aim of the present study was to analyze TSG profiles in stimulated leukocytes from dogs to identify genes that discriminate an activated phenotype. A total of 554 TSGs and three gene set collections were analyzed from microarray data. Cluster analysis of three subsets of genes discriminated between stimulated and unstimulated cells. These included 20 most upregulated and downregulated TSGs, TSG in hallmark gene sets significantly enriched in active cells, and a selection of candidate TSGs, p15 (CDKN2B), p18 (CDKN2C), p19 (CDKN1A), p21 (CDKN2A), p27 (CDKN1B), and p53 (TP53) in the third set. Analysis of two subsets suggested that these genes or a subset of these genes may be used as a specialized PCR set for additional analysis.