Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling

Exogenous dietary fat can induce obesity and promote diabetes, but endogenous fat production is not thought to affect skeletal muscle insulin resistance, an antecedent of metabolic disease. Unexpectedly, the lipogenic enzyme fatty acid synthase (FAS) was increased in the skeletal muscle of mice with diet-induced obesity and insulin resistance. Skeletal muscle–specific inactivation of FAS protected mice from insulin resistance without altering adiposity, specific inflammatory mediators of insulin signaling, or skeletal muscle levels of diacylglycerol or ceramide. Increased insulin sensitivity despite high-fat feeding was driven by activation of AMPK without affecting AMP content or the AMP/ATP ratio in resting skeletal muscle. AMPK was induced by elevated cytosolic calcium caused by impaired sarco/endoplasmic reticulum calcium ATPase (SERCA) activity due to altered phospholipid composition of the sarcoplasmic reticulum (SR), but came at the expense of decreased muscle strength. Thus, inhibition of skeletal muscle FAS prevents obesity-associated diabetes in mice, but also causes muscle weakness, which suggests that mammals have retained the capacity for lipogenesis in muscle to preserve physical performance in the setting of disrupted metabolic homeostasis

Review on Wave Energy Technologies and Power Equipment for Tropical Reefs

As a promising renewable resource to replace part of the energy supply, the wave energy is having more and more interest worldwide. This paper presents a comprehensive analysis of different wave energy technologies in order to identify more promising methods for power supply to tropical reefs. It starts with summarizing the characteristics of tropical reefs in which the most suitable places to be exploited are shown, and the classification of different types of wave energy converters according to their construction features. It is also described in detail each of the stages that are part of the energy conversion. On the basis of the characteristics of tropical coral reefs, the paper puts forward a new type of raft wave energy device which can achieve high operational reliability and adaptability with cost-effective deployment

Computer Assisted Relief Generation - a Survey

In this paper we present an overview of the achievements accomplished to date in the field of computer aided relief generation. We delineate the problem, classify the different solutions, analyze similarities, investigate the evelopment and review the approaches according to their particular relative strengths and weaknesses. In consequence this survey is likewise addressed to researchers and artists through providing valuable insights into the theory behind the different concepts in this field and augmenting the options available among the methods presented with regard to practical application

Detection of microaneurysms in retinal images using an ensemble classifier

This paper introduces, and reports on the performance of, a novel combination of algorithms for automated microaneurysm (MA) detection in retinal images. The presence of MAs in retinal images is a pathognomonic sign of Diabetic Retinopathy (DR) which is one of the leading causes of blindness amongst the working age population. An extensive survey of the literature is presented and current techniques in the field are summarised. The proposed technique first detects an initial set of candidates using a Gaussian Matched Filter and then classifies this set to reduce the number of false positives. A Tree Ensemble classifier is used with a set of 70 features (the most commons features in the literature). A new set of 32 MA groundtruth images (with a total of 256 labelled MAs) based on images from the MESSIDOR dataset is introduced as a public dataset for benchmarking MA detection algorithms. We evaluate our algorithm on this dataset as well as another public dataset (DIARETDB1 v2.1) and compare it against the best available alternative. Results show that the proposed classifier is superior in terms of eliminating false positive MA detection from the initial set of candidates. The proposed method achieves an ROC score of 0.415 compared to 0.2636 achieved by the best available technique. Furthermore, results show that the classifier model maintains consistent performance across datasets, illustrating the generalisability of the classifier and that overfitting does not occur

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Enzymatic Resolution of \u3b1-Methyleneparaconic Acids and Evaluation of their Biological Activity

Both enantiomers of three biologically relevant paraconic acids\u2014MB-3, methylenolactocin, and C75\u2014were obtained with enantioselectivities up to 99% by kinetic enzymatic resolutions. Good enantiomeric excesses were obtained for MB-3 and methylenolactocin, using \u3b1-chymotrypsin and aminoacylase as enantiocomplementary enzymes, while C75 was resolved with aminoacylase. They all were evaluated for their antiproliferative, antibacterial, and antifungal activities, showing weak effects and practically no difference between enantiomers in each case. At high concentrations (16\u201364 \u3bcg/mL), (\u2013)- C75 acted as an antimicrobial agent against Gram-positive bacteria

Aberrant lipid metabolism: an emerging diagnostic and therapeutic target in ovarian cancer

Ovarian cancer remains the most lethal gynaecological cancer. A better understanding of the molecular pathogenesis of ovarian cancer is of critical importance to develop early detection tests and identify new therapeutic targets that would increase survival. Cancer cells depend on de novo lipid synthesis for the generation of fatty acids to meet the energy requirements for increased tumour growth. There is increasing evidence that lipid metabolism is deregulated in cancers, including ovarian cancer. The increased expression and activity of lipogenic enzymes is largely responsible for increased lipid synthesis, which is regulated by metabolic and oncogenic signalling pathways. This article reviews the latest knowledge on lipid metabolism and the alterations in the expression of lipogenic enzymes and downstream signalling pathways in ovarian cancer. Current developments for exploiting lipids as biomarkers for the detection of early stage ovarian cancer and therapeutic targets are discussed. Current research targeting lipogenic enzymes and lipids to increase the cytotoxicity of chemotherapy drugs is also highlighted.Carmen E. Pyragius, Maria Fuller, Carmela Ricciardelli and Martin K. Oehle

Unicystic ameloblastoma of the mandible - an unusual case report and review of literature

Ameloblastoma is a true neoplasm of odontogenic epithelial origin. It is the second most common odontogenic neoplasm, and only odontoma outnumbers it in reported frequency of occurrence. Its incidence, combined with its clinical behavior, makes ameloblastoma the most significant odontogenic neoplasm. Unicystic ameloblastoma (UA) refers to those cystic lesions that show clinical, radiographic, or gross features of a mandibular cyst, but on histologic examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor growth. It accounts for 5-15% of all intraosseous ameloblastomas. We report a case of unicystic ameloblastoma in a 30-year-old female, and review the literature

SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway