243 research outputs found

    Embracing the complexity of matricellular proteins : the functional and clinical significance of splice variation

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    Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets

    Complicated objects: artifacts from the Yuanming Yuan in Victorian Britain

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    The 1860 spoliation of the Summer Palace at the close of the Second Opium War by British and French troops was a watershed event within the development of Britain as an imperialist nation, which guaranteed a market for opium produced in its colony India and demonstrated the power of its armed forces. The distribution of the spoils to officers and diplomatic corps by campaign leaders in Beijing was also a sign of the British Army’s rising power as an instrument of the imperialist state. These conditions would suggest that objects looted from the site would be integrated into an imperialist aesthetic that reflected and promoted the material benefits of military engagement overseas and foregrounded the circumstances of their removal to Britain for campaign members and the British public. This study mines sources dating to the two decades following the war – including British newspapers, auction house records, exhibition catalogs and works of art – to test this hypothesis. Findings show that initial movements of looted objects through the military and diplomatic corps did reinforce notions of imperialist power by enabling campaign members to profit from the spoliation through sales of looted objects and trophy displays. However, material from the Summer Palace arrived at a moment when British manufacturers and cultural leaders were engaged in a national effort to improve the quality of British goods to compete in the international marketplace and looted art was quickly interpolated in this national conversation. Ironically, the same “free trade” imperatives that motivated the invasion energized a new design movement that embraced Chinese ornament. As a consequence, political interpretations of the material outside of military collections were quickly joined by a strong response to Chinese ornament from cultural institutions and design leaders. Art from the Summer Palace held a prominent place at industrial art exhibitions of the postwar period and inspired new designs in a number of mediums. While the availability of Chinese imperial art was the consequence of a military invasion and therefore a product of imperialist expansion, evidence presented here shows that the design response to looted objects was not circumscribed by this political reality. Chinese ornament on imperial wares was ultimately celebrated for its formal qualities and acknowledged links to the Summer Palace were an indicator of good design, not a celebration of victory over a failed Chinese state. Therefore, the looting of the Summer Palace was ultimately an essential factor in the development of modern design, the essence of which is a break with Classical ornament

    Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

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    Background: Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses. Method: Male SHR, Wistar-Kyoto (WKY) and Wistar rats (WIS) were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s) between post-natal days (PND) 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of responsereinforcement functions (Herrnstein’s hyperbola) and bout-organized behavior were estimated in each epoch. Results: SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute), and particularly in the second epoch. Estimates of Herrnstein’s hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential

    Discipline in Context: Suspension, Climate, and PBIS in the School District of Philadelphia

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    The report details a two-year exploratory, mixed-methods research study on the disciplinary practices and climate of schools serving K–8 students in the School District of Philadelphia (SDP). Findings reveal that SDP schools are making efforts to reduce suspensions and improve climate, but critical barriers to these efforts include resource limitations and philosophical misalignments between teachers and school leaders. The study identified three profiles among SDP schools serving K–8 students based on information about disciplinary practices and climate, and found that these profiles are predictive of suspension and academic outcomes. Students attending schools with collaborative climates and less punitive approaches to discipline have lower risk of being suspended and better academic outcomes. The report offers a series of recommendations for strengthening the implementation of climate initiatives, including Positive Behavioral Interventions and Supports (PBIS), in challenging urban settings

    Discipline in Context: Suspension, Climate, and PBIS in the School District of Philadelphia

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    The report details a two-year exploratory, mixed-methods research study on the disciplinary practices and climate of schools serving K–8 students in the School District of Philadelphia (SDP). Findings reveal that SDP schools are making efforts to reduce suspensions and improve climate, but critical barriers to these efforts include resource limitations and philosophical misalignments between teachers and school leaders. The study identified three profiles among SDP schools serving K–8 students based on information about disciplinary practices and climate, and found that these profiles are predictive of suspension and academic outcomes. Students attending schools with collaborative climates and less punitive approaches to discipline have lower risk of being suspended and better academic outcomes. The report offers a series of recommendations for strengthening the implementation of climate initiatives, including Positive Behavioral Interventions and Supports (PBIS), in challenging urban settings

    Perinatal Cat and Dog Exposure and the Risk of Asthma and Allergy in the Urban Environment: A Systematic Review of Longitudinal Studies

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    Background. The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood. Methods. Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease. Results. Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion. Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required

    Paracetamol use in early life and asthma: prospective birth cohort study

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    Objective To determine if use of paracetamol in early life is an independent risk factor for childhood asthma
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