Activation of AMP-activated protein kinase by metformin induces protein acetylation in prostate and ovarian cancer cells

AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription. Nucleocytosolic concentration of acetyl-CoA affects histone acetylation and links metabolism and chromatin structure. Here we show that activation of AMPK with the widely used antidiabetic drug metformin or with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide increases the inhibitory phosphorylation of ACC and decreases the conversion of acetyl-CoA to malonyl-CoA, leading to increased protein acetylation and altered gene expression in prostate and ovarian cancer cells. Direct inhibition of ACC with allosteric inhibitor 5-(tetradecyloxy)-2-furoic acid also increases acetylation of histones and non-histone proteins. Because AMPK activation requires liver kinase B1, metformin does not induce protein acetylation in liver kinase B1-deficient cells. Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin's physiological effects

A measurement of the audible vocabulary level of selected television programs

The problem that this paper was concerned with was a measurement of the audible vocabulary level of selected television programs

Food safety and ICT traceability systems: Lessons from Japan for developing countries

The increasing number of food safety problems occurring worldwide in recent years has heightened consumers' food safety awareness and has caused public distrust of the increasingly complex and globalized food production and trading system. Establishing a food traceability system could improve consumers' confidence and address the documentation requirements required under multinational and bilateral trade agreements. Food traceability systems are therefore becoming critical for the food industry and the public sector, as well as for consumers. The increased requirements for documentation and reporting systems are taking a toll on developing countries that are hoping to expand their trade in food or break into new markets. Smallholder farmers in particular could be further marginalized from the global food trading system by the burden of the reporting requirements. This paper reviews experiences in using information and communications technology (ICT) to create efficient traceability systems and make information more easily available to consumers. Case studies from Japan, where the use of ICT in food traceability systems is relatively advanced, reveal lessons for developing countries. The paper examines institutional arrangements, hardware and software requirements, costs of operation, roles of the public and private sectors, and the impacts of two food traceability systems (one for dried shiitake mushrooms, the other for poultry products, both by smallholder farmers). The two case studies show how ICT can help to establish an efficient traceability system and improve consumers' confidence in the products. They also show that collaboration between public and private sectors is a key to success. The traceability systems facilitate improved efficiency in the management of the supply chain. At the same time, in the event of a food safety incident, the source of the problem can be more quickly identified and appropriate action taken. It is expected that traceability systems will be increasingly adopted in food-exporting countries as a strategy to improve competitiveness in the global food market

Hippocampal Interneuron Dynamics Supporting Memory Encoding and Consolidation

Neural circuits within the hippocampus, a mammalian brain structure critical for both the encoding and consolidation of episodic memories, are composed of intimately connected excitatory pyramidal cells and inhibitory interneurons. While decades of research have focused on how the in vivo physiological properties of pyramidal cells may support these cognitive processes, and the anatomical and physiological properties of interneurons have been extensively studied in vitro, relatively little is known about how the in vivo activity patterns of interneurons support memory encoding and consolidation. Here, I have utilized Acousto-Optic Deflection (AOD)-based two-photon calcium imaging and post-hoc immunohistochemistry to perform large-scale recordings of molecularly-defined interneuron subtypes, within both CA1 and CA3, during various behavioral tasks and states. I conclude that the subtype-specific dynamics of inhibitory circuits within the hippocampus are critical in supporting its role in memory encoding and consolidation

Evaluation of In-Situ variability of concrete pavement characteristics and their effect on performance

University of Minnesota Ph.D. dissertation. December 2013. Major: Civil Engineering. Advisor: Lev Khazanovich. 1 computer file (PDF); viii, 138 pages, appendices A-B.Pavement performance prediction must account for uncertainties in pavement characteristics, climate, traffic loading, etc. Past research identified that concrete thickness and flexural strength were two pavement characteristics that significantly affected transverse cracking in Jointed Plain Concrete Pavements (JPCP). This dissertation concentrated on quantifying the effect of concrete thickness variability and, to a lesser extent, flexural strength variability on the reliability analysis of jointed plain concrete pavement (JPCP) performance. Concrete thickness is typically assessed by measuring the length of concrete cores, but this procedure limits the amount of information collected. The possibility of using non-destructive testing to assess concrete thickness was evaluated and significant efforts were dedicated to quantification of the variability of constructed pavement concrete thickness and determination of requirements for thickness sampling spacing using autocorrelation concepts. The Mechanistic Empirical Pavement Design Guide (MEPDG) is a tool used to evaluate the performance of JPCP, which predicts pavement distresses based on a desired reliability of design. MEPDG's current reliability analysis does not allow the MEPDG to quantify the effect of improved material characterization prior to design or the effect of quality control on pavement performance. In this study, a method to account for pavement characteristic variability in the reliability analysis is presented and evaluated the measured variability of rigid pavement concrete thickness and flexural strength