Diverse fossil epacrids (Styphelioideae; Ericaceae) from early Pleistocene sediments at Stony Creek Basin, Victoria, Australia

There is currently intense interest in the radiation of the scleromorphic groups that dominate the Australian flora, but at present, only Proteaceae and Casuarinaceae have fossil records detailed enough to provide useful evidence on the timing of these radiations. This article records a diverse assemblage of fossil leaves of another major scleromorphic group, the epacrids (subfamily Styphelioideae of Ericaceae, formerly known as Epacridaceae). The fossils are from Stony Creek Basin, in the western uplands of Victoria, Australia, and are of earliest Pleistocene age (ca. 1.6 million years old). They include 19 forms sufficiently distinct as to constitute different species. This diversity is considerably greater than the extant diversity of epacrids in the region. Published taphonomic data are used to argue that the actual diversity of the source vegetation of the fossil flora may have been significantly greater and comparable to the current local species richness of the centers of diversity. Ten of the fossil species are assigned to the largest extant tribe (Styphelieae), eight are assigned to Epacrideae or Archerieae, and one is assigned to Cosmelieae. This evidence is used to argue that substantial radiation of the epacrids had occurred by the beginning of the Pleistocene

Remnant cholesterol predicts progression of diabetic nephropathy and retinopathy in type 1 diabetes

Background We aimed to assess whether remnant cholesterol concentration and variability predict the progression of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR) in type 1 diabetes. Methods This observational prospective study covered 5150 FinnDiane Study participants. Remnant cholesterol was calculated as total cholesterol - LDL cholesterol - HDL cholesterol and variability as the coefficient of variation. DN category was based on consensus albuminuria reference limits and the progression status was confirmed from medical files. SDR was defined as retinal laser treatment. For 1338 individuals, the severity of diabetic retinopathy (DR) was graded using the ETDRS classification protocol. Median (IQR) follow-up time was 8.0 (4.9-13.7) years for DN and 14.3 (10.4-16.3) for SDR. Results Remnant cholesterol (mmol L-1) was higher with increasing baseline DN category (P < 0.001). A difference was also seen comparing non-progressors (0.41 [0.32-0.55]) with progressors (0.55 [0.40-0.85]), P < 0.001. In a Cox regression analysis, remnant cholesterol predicted DN progression, independently of diabetes duration, sex, HbA(1c), systolic blood pressure, smoking, BMI, estimated glucose disposal rate and estimated glomerular filtration rate (HR: 1.51 [1.27-1.79]). Remnant cholesterol was also higher in those who developed SDR (0.47 [0.36-0.66]) than those who did not (0.40 [0.32-0.53]), P < 0.001, and the concentration increased stepwise with increasing DR severity (P < 0.001). Regarding SDR, the HR for remnant cholesterol was 1.52 (1.26-1.83) with the most stringent adjustment. However, remnant cholesterol variability was not independently associated with the outcomes. Conclusions Remnant cholesterol concentration, but not variability, predicts DN progression and development of SDR. However, it remains to be elucidated whether the associations are causal or not.Peer reviewe

Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

OBJECTIVE—To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men

Evaluating policy as argument: the public debate over the first UK austerity budget

This article aims to make a methodological contribution to the ‘argumentative turn’ in policy analysis and to the understanding of the public debate on the UK Government's austerity policies. It suggests that policy arguments are practical arguments from circumstances, goals and means–goal relations to practical conclusions (proposals) that can ground decision and action. Practical proposals are evaluated in light of their potential consequences. This article proposes a deliberation scheme and a set of critical questions for the evaluation of deliberation and decision-making in conditions of incomplete knowledge (uncertainty and risk). It illustrates these questions by analysing a corpus of articles from five newspapers over the two months following the adoption of the first austerity budget in June 2010. It also suggests how analysis of ‘frames’ and ‘framing’ can be integrated with the evaluation of deliberation and decision-making

ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes

International audienceBACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-)Apob(100/100)). CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome

Evaluation of the pleiotropic effects of statins:a reanalysis of the randomized trial evidence using Egger regression

Objective— To reanalyze data from recent randomized trials of statins to assess whether the benefits and risks of statins are mediated primarily via their LDL-C (low-density lipoprotein cholesterol) lowering effects or via other mechanisms. Approach and Results— We adapted Egger regression, a technique frequently used in Mendelian randomization studies to detect genetic pleiotropy, to reanalyze the available randomized control trial data of statin therapy. For cardiovascular end points, each 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 0.77 (95% confidence interval, 0.71–0.84) with an intercept that was indistinguishable from zero (intercept, −0.0032; [95% confidence interval, −0.090 to 0.084]; P =0.94), indicating no pleiotropy. For incident diabetes mellitus, a 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 1.07 (95% confidence interval, 0.99–1.16) and an intercept nondistinguishable from zero (intercept, −0.015; [95% confidence interval, −0.30 to 0.27]; P =0.91), again indicating no pleiotropy. Conclusions— Our reanalysis of the randomized control trial data using Egger regression adds to the existing evidence that the cardiovascular benefits of statins and their association with incident diabetes mellitus are mediated primarily, if not entirely, via their LDL-C lowering properties rather than by any pleiotropic effects. </jats:sec