Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse

In the isolated rat carotid artery, the endocannabinoid anandamide induces endothelium-dependent relaxation via activation of the enzyme sphingosine kinase (SK). This generates sphingosine-1-phosphate (S1P) which can be released from the cell and activates S1P receptors on the endothelium. In anaesthetised mice, anandamide has a well-characterised triphasic effect on blood pressure but the contribution of SK and S1P receptors in mediating changes in blood pressure has never been studied. Therefore, we assessed this in the current study. The peak hypotensive response to 1 and 10 mg/kg anandamide was measured in control C57BL/6 mice and in mice pretreated with selective inhibitors of SK1 (BML-258, also known as SK1-I) or SK2 ((R)-FTY720 methylether (ROMe), a dual SK1/2 inhibitor (SKi) or an S1P1 receptor antagonist (W146). Vasodilator responses to S1P were also studied in isolated mouse aortic rings. The hypotensive response to anandamide was significantly attenuated by BML-258 but not by ROMe. Antagonising S1P1 receptors with W146 completely blocked the fall in systolic but not diastolic blood pressure in response to anandamide. S1P induced vasodilation in denuded aortic rings was blocked by W146 but caused no vasodilation in endothelium-intact rings. This study provides evidence that the SK1/S1P regulatory-axis is necessary for the rapid hypotension induced by anandamide. Generation of S1P in response to anandamide likely activates S1P1 to reduce total peripheral resistance and lower mean arterial pressure. These findings have important implications in our understanding of the hypotensive and cardiovascular actions of cannabinoids

Cognitive representations of disability behaviours in people with mobility limitations : consistency with theoretical constructs

Disability is conceptualised as behaviour by psychological theory and as a result of bodily impairment by medical models. However, how people with disabilities conceptualise those disabilities is unclear. The purpose of this study was to examine disability representations in people with mobility disabilities. Thirteen people with mobility disabilities completed personal repertory grids (using the method of triads) applied to activities used to measure disabilities. Ten judges with expertise in health psychology then examined the correspondence between the elicited disability constructs and psychological and medical models of disability. Participants with mobility disabilities generated 73 personal constructs ofdisability. These constructs were judged consistent with the content of two psychological models, namely the theory of planned behaviour and social cognitive theory and with the main medical model of disability, the International Classification of Functioning Disability and Health.Individuals with activity limitations conceptualise activities in a manner that is compatible with both psychological and medical models. This ensures adequate communication in contexts where the medical model is relevant, e.g. clinical contexts, as well as in everyday conversation about activities and behaviours. Finally, integrated models of disability may be of value for theory driven interdisciplinary approaches to disability and rehabilitation

Keratinocyte Carcinomas:Current concepts and future research priorities

Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas (KC), the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in KC tumorigenesis and tumor characteristics which have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of KC continue to increase, strategies for prevention, including effective sun protective behavior, educational interventions and reduction of tanning bed access and usage are essential. Gaps in our knowledge requiring additional research in order to reduce the high morbidity and costs associated with KC include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.</p

Bottom sediments of Lake Rotoma

Lake Rotoma is a deep (70-80 m), oligotrophic, warm monomictic lake of volcanic origin with insignificant stream inflow and no clearly defined outflow. For at least 60 years up to 1972 the lake level fluctuated markedly about an overall rising trend of some 6-10 m. Nearshore profiles are related to the prevailing wave climate superimposed upon the overall rising lake level, shelves being wider, less steep, and deeper about the more exposed eastern and southern shorelines. The outer portions of shelves extending well below modern storm wave base into waters as deep as 15-25 m are relict features from lower lake level stands. Sediments fine from sand-gravel mixtures nearshore to silts in basinal areas. Their composition reflects a composite provenance involving the lavas and tephras about the lake, as well as intralake diatom frustules and organic matter. The distribution pattern of surficial bottom sediments is an interplay between grains of both biological and terrigenous origin, supplied presently and in the past by a variety of processes, that have been dispersed either by the modern hydrodynamic regime or by former ones associated with lower lake levels. These interrelationships are structured by erecting 5 process-age sediment classes in the lake, namely neoteric, amphoteric, proteric, palimpsest, and relict sediments, analogous to categories postulated for sediments on oceanic continental shelves. Short-core stratigraphy includes the Kaharoa (A.D. -1020) and Tarawera (A.D. 1886) tephras. The rates of sedimentation of diatomaceous silts in basinal areas have more than doubled since the Tarawera eruption, indicating an overall increase in the fertility level of lake waters associated, perhaps, with recent farm development in the catchment

Visuo-spatial cognition in Williams syndrome: Reviewing and accounting for the strengths and weaknesses in performance

Individuals with Williams syndrome typically show relatively poor visuo-spatial abilities in comparison to stronger verbal skills. However, individuals' level of performance is not consistent across all visuo-spatial tasks. The studies assessing visuo-spatial functioning in Williams syndrome are critically reviewed, in order to provide a clear pattern of the relative difficulty of these tasks. This prompts a possible explanation of the variability in performance seen which focuses on the processing demands of some of these tasks. Individuals with Williams syndrome show an atypical processing style on tests of construction, which does not affect tests of perception

The social consequences of minor innovations in construction

Innovation studies in construction focus on a desire to increase economics and efficiency at a large scale. This has resulted in a skewed perspective that sees only major corporations with substantial R&D resources, complex projects, or national interests at the heart of innovation. By adopting anthropological methods, it becomes possible to examine the two aims of this paper: to demonstrate that an accumulation of minor innovations can have significant consequences; and to show that these are inherently social rather than purely economic. Results come from fieldwork studying the improvisatory house-building practices of the Kelabit people of rural Borneo, tracing changes to the technologies used for roofing and foundations, and describes how these are mutually entangled with new social structures. The conclusion is that we should think more broadly about the forms and effects of innovation in construction, and recognise the significance of improvisation at the level of the individual or small group

Cornish identities and migration: a multi-scalar approach

The definitive version is available at www.blackwell-synergy.com. 24 month embargo by the publisher. Article will be released July 2009.In this article we argue that theories of transnationalism have value in exploring the historical context of migration and that historical contexts help to shape such theoretical conceptualizations. Historians of migration have now begun to engage more directly with the literature of transnationalism, focusing on the networks that linked settler and home communities. Here we add to this by examining a nineteenth-century migrant community from a British region through the lens of transnationalism, applying the concept to the case of the Cornish, whose economic specialization produced culturally distinct Cornish communities on the mining frontiers of North America, Australia and South Africa. In doing so, we bring together the issues of scale and time. We review the multiple levels of the Cornish transnational space of the late nineteenth century, which exhibited aspects of both core transnationalism and translocalism. This waned, but in the later twentieth century, a renewed interest in a transnational Cornish identity re-emerged, articulating with changing identity claims in Cornwall itself. To capture better the experience of the Cornish over these two very different phases of transnationalism we identify another subset of transnationalism - that of transregionalism.Leverhulme Trus

Broken Rituals: Contending Gods and Sacred Cows in Religious Racial Reconciliation and Race Relations

Race remains one of the most important determinants of a host of sociological outcomes despite claims that social characteristics such as class matter more. For example, racial inequalities are apparent in educational outcomes and regarding to asset-ownership. Perhaps the most troubling evidence of persistent racial inequities is the killing of Black people by law enforcement officials or civilians while they are engaged in such mundane activities, such as jogging in a neighborhood or selling compact discs (CDs). In the aftermath of these unnatural killings, there are often calls for racial reconciliation, faith based racial reconciliation. In times where it appears that the worst of humanity is on full display, many people, including many Americans, look to religious institutions, religious tradition, and religious leaders for guidance. Many sociologists have expressed an interest in understanding why Americans look to religion, how religious groups and institutions have responded, and what are some best practices. This research has been limited in important ways. For example, in the last quarter century, sociologists and other scholars studying religious, racial reconciliation and race relations have regarded both Black and White “racial” groups as homogenic groupings, and consequently ignore variations in the American religious universe, especially among American Blacks. The question of whether current religious sociological frames can accurately describe, explain, or make predictions about the successes or failures of racial, religious reconciliation then arises. Sociological research on racial and religious reconciliation is also limited by a conventional definition of religion. To address that limitation, I use Charles Long’s definition, where religion is understood as an orientation. I engaged in a longitudinal qualitative study focused on groups and individuals attempting to implement religious remedies in areas of high impact racial events. The primary group in which I was embedded included up too 1100 residents in Baton Rouge, with a focus on v responses to the killings of unarmed Black people from Trayvon Martin to George Floyd. It is anticipated that what I call the hidden gods and “sacred cows,” govern issues of race in modern America that impact whether racial, religious reconciliation is possible. The theoretical, methodological, and public policy implications of the proposed study are identified here