Description: In obesity, reduced cardiac glucose uptake and mitochondrial abnormalities are putative causes of cardiac dysfunction. However, high-fat diet (HFD) does not consistently induce cardiac insulin resistance and mitochondrial damage, and recent studies suggest HFD may be cardioprotective. To determine cardiac responses to HFD, we investigated cardiac function, glucose uptake, and mitochondrial respiration in young (3-month-old) and middle-aged (MA) (12-month-old) male Ldlr –/– mice fed chow or 3 months HFD to induce obesity, systemic insulin resistance, and hyperinsulinemia. In MA Ldlr –/– mice, HFD induced accelerated atherosclerosis and nonalcoholic steatohepatitis, common complications of human obesity. Surprisingly, HFD-fed mice demonstrated increased cardiac glucose uptake, which was most prominent in MA mice, in the absence of cardiac contractile dysfunction or hypertrophy. Moreover, hearts of HFD-fed mice had enhanced mitochondrial oxidation of palmitoyl carnitine, glutamate, and succinate and greater basal insulin signaling compared with those of chow-fed mice, suggesting cardiac insulin sensitivity was maintained, despite systemic insulin resistance. Streptozotocin-induced ablation of insulin production markedly reduced cardiac glucose uptake and mitochondrial dysfunction in HFD-fed, but not in chow-fed, mice. Insulin injection reversed these effects, suggesting that insulin may protect cardiac mitochondria during HFD. These results have implications for cardiac metabolism and preservation of mitochondrial function in obesity.

Description: Background The epithelial–mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells. Methods Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan–Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided. Results The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14 x 10 –4 ) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01 x 10 –4 ). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells. Conclusions The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies.

Description: Microcystis is known to overwinter on sediment surfaces and provide an inoculum to support water column blooms in lakes. There is uncertainty as to whether recruitment is an active process triggered by internal changes in buoyancy, or a passive process induced by resuspension. The effect on Microcystis recruitment of ammonium, light and temperature was assessed in laboratory experiments using sediments collected in a small eutrophic lake from two habitats: near-edge (containing Microcystis and Aphanizomenon gracile ) and mid-lake (predominantly Microcystis ). In all experiments single cells, rather than colonies, accounted for the majority (〉55%) of recruited cells. Microcystis recruitment was significantly lower ( P  〈 0.001) in near-shore samples suggesting that A. gracile elicits allelopathic effects on Microcystis. In mid-lake samples, Microcystis recruitment was significantly higher at moderate ammonium concentrations (0.1, 0.2 and 0.5 mg L –1 ; P  〈 0.001), at two temperatures (16 and 25°C; P  〈 0.001) and high light intensities (50 and 100 µmol m –2 s –1 ; P  〈 0.01). Microcystis cells were isolated from sediment in spring, early and late summer and assessed using transmission electron microscopy. The percentage of cell area filled with gas vesicles increased significantly ( P  〈 0.001). These data demonstrate that allopathic interactions, ammonium, light and temperature can individually and synergistically regulate gas vesicle synthesis and Microcystis recruitment.

Description: Cyanobacteria are commonly associated with eutrophic lakes, where they often form blooms and produce toxins. However, they are a ubiquitous component of phytoplankton in lakes of widely varying trophic status. We hypothesised that cyanobacterial diversity would vary among lakes of differing trophic status, but that the relative importance of geographical and hydromorphological characteristics driving these patterns would differ across trophic groups. DNA from 143 New Zealand lakes that spanned a range of geographic, hydromorphological and trophic gradients was analysed using automated rRNA intergenic spacer analysis and screened for genes involved in cyanotoxin production. Statistical analysis revealed significant delineation among cyanobacterial communities from different trophic classes. Multivariate regression indicated that geographical features (latitude, longitude and altitude) were significant in driving cyanobacterial community structure; however, partitioning of their effects varied among trophic categories. High-throughput sequencing was undertaken on selected samples to investigate their taxonomic composition. The most abundant and diverse (71 operational taxonomic units) taxon across all lake types was the picocyanobacteria genus Synechococcus . Cyanotoxins (microcystins n = 23, anatoxins n = 1) were only detected in eutrophic lowland lakes. Collectively, these data infer that increasing eutrophication of lakes will have broad-scale impacts on planktonic cyanobacteria diversity and the prevalence of cyanotoxins.