Caffeine-stimulated fatty acid oxidation is blunted in CD36 null mice

Aim: The increase in skeletal muscle fatty acid metabolism during exercise has been associated with the release of calcium. We examined whether this increase in fatty acid oxidation was attributable to a calcium-induced translocation of the fatty acid transporter CD36 to the sarcolemma, thereby providing an enhanced influx of fatty acids to increase their oxidation.Methods: Calcium release was triggered by caffeine (3 mM) to examine fatty acid oxidation in intact soleus muscles of WT and CD36-KO mice, while fatty acid transport and mitochondrial fatty acid oxidation were examined in giant vesicles and isolated mitochondria, respectively, from caffeine-perfused hindlimb muscles of WT and CD36-KO mice. Western blotting was used to examine calcium-induced signalling.Results: In WT, caffeine stimulated muscle palmitate oxidation (+136%), but this was blunted in CD36-KO mice (-70%). Dantrolene inhibited (WT) or abolished (CD36-KO) caffeine-induced palmitate oxidation. In muscle, caffeine-stimulated palmitate oxidation was not attributable to altered mitochondrial palmitate oxidation. Instead, in WT, caffeine increased palmitate transport (+55%) and the translocation of fatty acid transporters CD36, FABPpm, FATP1 and FATP4 (26-70%) to the sarcolemma. In CD36-KO mice, caffeine-stimulated FABPpm, and FATP1 and 4 translocations were normal, but palmitate transport was blunted (-70%), comparable to the reductions in muscle palmitate oxidation. Caffeine did not alter the calcium-/calmodulin-dependent protein kinase II phosphorylation but did increase the phosphorylation of AMPK and acetyl-CoA carboxylase comparably in WT and CD36-KO.Conclusion: These studies indicate that sarcolemmal CD36-mediated fatty acid transport is a primary mediator of the calcium-induced increase in muscle fatty acid oxidation

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO

A VALUE PLATFORM ANALYSIS PERSPECTIVE ON CUSTOMER ACCESS INFORMATION TECHNOLOGY

Customer access information technologies (CAITs) provide a link between a firm and its customers. Firms invest in CAITs to reduce costs, increase revenues and market share, lock in existing customers and capture new ones. These benefits, however, are notoriously difficult to measure. This paper proposes an evaluative method for CAlT deployment called value platform analysis, that is based on a conceptual model drawn from the theory of retail outlet deployment in marketing science. The model focuses on the impact of CAIT features and environmental features on transactions generated by the CAIT. Specific econometric models are developed for deployment. Hypotheses regarding the likely impact of automated teller machine (ATM) location design choices and environmental features on ATM transactions are evaluated. The results indicate that there are a number of key features influencing ATM performance. Two distinct ATM deployment scenarios emerge: one for servicing a bank's own customers, and another for providing transaction services for customers for a fee.Information Systems Working Papers Serie

Gas generation over plutonium oxides in the 94-1 shelf-life surveillance program.

The Department of Energy (DOE) is embarking upon a program to store large quantities of plutonium-bearing materials for up to fifty years. The Los Alamos National Laboratory Shelf Life Project was established to bound the behavior of plutonium-bearing material meeting the DOE 3013 Standard. The shelf life study monitors temperature, pressure and gas composition over oxide materials in a limited number of large-scale 3013 inner containers and in many small-scale containers. For the large-scale study, baseline plutonium oxides, oxides exposed to high-humidity atmospheres, and oxides containing chloride salt impurities are planned. The first large-scale container represents a baseline and contains dry plutonium oxide prepared according to the 3013 Standard. This container has been observed for pressure, temperature and gas compositional changes for less than a year. Results indicate that no detectable changes in pressure and gas composition are observed

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.

This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres

A Geologically Based Indoor-Radon Potential Map of Kentucky

We combined 71,930 short-term (median duration 4 days) home radon test results with 1:24,000-scale bedrock geologic map coverage of Kentucky to produce a statewide geologically based indoor-radon potential map. The test results were positively skewed with a mean of 266 Bq/m3, median of 122 Bq/m3, and 75th percentile of 289 Bq/m3. We identified 106 formations with ≥10 test results. Analysis of results from 20 predominantly monolithologic formations showed indoor-radon concentrations to be positively skewed on a formation-by-formation basis, with a proportional relationship between sample means and standard deviations. Limestone (median 170 Bq/m3) and dolostone (median 130 Bq/m3) tended to have higher indoor-radon concentrations than siltstones and sandstones (median 67 Bq/m3) or unlithified surficial deposits (median 63 Bq/m3). Individual shales had median values ranging from 67 to 189 Bq/m3; the median value for all shale values was 85 Bq/m3. Percentages of values falling above the U.S. Environmental Protection Agency (EPA) action level of 148 Bq/m3 were sandstone and siltstone: 24%, unlithified clastic: 21%, dolostone: 46%, limestone: 55%, and shale: 34%. Mississippian limestones, Ordovician limestones, and Devonian black shales had the highest indoor-radon potential values in Kentucky. Indoor-radon test mean values for the selected formations were also weakly, but statistically significantly, correlated with mean aeroradiometric uranium concentrations. To produce a map useful to nonspecialists, we classified each of the 106 formations into five radon-geologic classes on the basis of their 75th percentile radon concentrations. The statewide map is freely available through an interactive internet map service

An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations

The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins

What Every Business Student Needs to Know About Information Systems

Whether Information Systems should or should not be part of the core business school curriculum is a recurring discussion in many universities. In this article, a task force of 40 prominent information systems scholars address the issue. They conclude that information systems is absolutely an essential body of knowledge for business school students to acquire as well as a key element of the business school\u27s long-run strategic positioning within the university. Originally prepared in response to draft accreditation guidelines prepared by AACSB International, the article includes a compilation of the concepts that the authors believe to be the core information systems knowledge that all business school students should be familiar with

An enterprise engineering approach for the alignment of business and information technology strategy

Information systems and information technology (IS/IT, hereafter just IT) strategies usually depend on a business strategy. The alignment of both strategies improves their strategic plans. From an external perspective, business and IT alignment is the extent to which the IT strategy enables and drives the business strategy. This article reviews strategic alignment between business and IT, and proposes the use of enterprise engineering (EE) to achieve this alignment. The EE approach facilitates the definition of a formal dialog in the alignment design. In relation to this, new building blocks and life-cycle phases have been defined for their use in an enterprise architecture context. This proposal has been adopted in a critical process of a ceramic tile company for the purpose of aligning a strategic business plan and IT strategy, which are essential to support this process. © 2011 Taylor & Francis.Cuenca, L.; Boza, A.; Ortiz, A. (2011). 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