Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-a(2)-glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. RESULTS: Treatment of these animals for 15 days with ZAG (100? µg, intravenously, daily) resulted in a reduction of body weight of 6.55? g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4?°C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli

A mitochondrial encephalomyopathy with a partial cytochrome c oxidase deficiency of muscle.

A 16 year old girl showed delayed psychomotor development. In infancy, exercise intolerance, cerebellar signs, deteriorated with increasing intercurrent infections, and disturbances of breathing and cardiac rhythm became manifest. From the age of 7 years there was chronic progressive psychomotor deterioration, with hypotonia, a bilateral pyramidal and cerebellar syndrome, and mild epilepsy. CSF pyruvate and lactate levels were elevated, and lactate content was elevated in the urine. There was an abnormally high rise of lactate levels on moderate exercise and an abnormal response to pyruvate loading. Quadriceps muscle biopsies obtained at age 10 and 16 years showed ragged-red fibres, and a decreased cytochrome c oxidase activity and cytochrome aa3 content. Cytochrome c oxidase activity in fibroblasts was normal. Clinical signs and symptoms in association with a disturbance of mitochondrial energy metabolism led us to diagnosis of probable Leigh syndrome

The circulation of flesh: regional food producing/consuming systems in Southern England 1500BC-AD1086

It has become an axiom of British archaeology that the results of developer-funded fieldwork are under-utilised in research and several projects carried out at British universities have attempted to redress this perceived imbalance. These projects, including those on British and Continental prehistory carried out by Richard Bradley, the Roman Rural settlement project, the Fields of Britannia project, John Blair's work on early medieval England and the EngLaId project, of which this thesis forms a component, have all demonstrated beyond doubt the transformative effect of the data produced by developer-funded work on our understanding. However, to date no project has sought to utilise artefact and ecofact data produced by developer-funded work on a similar scale. This thesis is partly an attempt to fill this gap, by using ceramic, animal bone and charred plant data from digital archives generated by developer-funded archaeology, to address a series of questions about food production/consumption over the later prehistoric and early historic periods in Southern England. These three datasets have very varied characteristics and their integration in a single database was, therefore, one of the major challenges of the thesis. However, this also provided the opportunity to ask new questions and to address old questions with new data. The thesis argues that regional ecosystems had a long-term influence on processes of food production/consumption, which displayed considerable continuities across the boundaries of traditional archaeological periods. Landscape, settlement, ceramic, animal bone and charred plant data from three regional case studies, encompassing the Upper Thames Valley, the Middle and Lower Thames Valley and the route of HS1 in Kent were investigated using a Filemaker database and QGIS mapping. It is argued that, while there were long-term continuities in the use of plants and animals, the expression of social relationships expressed in fields, settlements and ceramics followed a cyclical pattern.</p

Big, bad (?) data: new approaches to the study of food, identity and landscape in early medieval England

A Big Data study of ceramics, animal bone, charred plant remains and stable isotopes in the context of the Oxford-based English Landscapes and Identities (EngLaId) project