Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium

AbstractIschemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied.The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 ± 0.14 versus 0.15 ± 0.10 μmol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to >90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%).These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose becomes an important myocardial substrate under these pathologic conditions

Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells

Mercury flux to sediments of Lake Tahoe, California-Nevada

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Water, Air, & Soil Pollution 210 (2010): 399-407, doi:10.1007/s11270-009-0262-y.We report estimates of mercury (Hg) flux to the sediments of Lake Tahoe, California-Nevada: 2 and 15-20 µg/m2/yr in preindustrial and modern sediments, respectively. These values result in a modern to preindustrial flux ratio of 7.5-10, which is similar to flux ratios recently reported for other alpine lakes in California, and greater than the value of 3 typically seen worldwide. We offer plausible hypotheses to explain the high flux ratios, including (1) proportionally less photoreduction and evasion of Hg with the onset of cultural eutrophication and (2) a combination of enhanced regional oxidation of gaseous elemental Hg and transport of the resulting reactive gaseous Hg to the surface with nightly downslope flows of air. If either of these mechanisms is correct, it could lead to local/regional solutions to lessen the impact of globally increasing anthropogenic emissions of Hg on Lake Tahoe and other alpine ecosystems.Funding was provided by Miami University, EPA-STAR, the Postdoctoral Scholar Program at Woods Hole Oceanographic Institution, and the USGS

N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis

The rising incidence of antimicrobial resistance (AMR) makes it imperative to understand the underlying mechanisms. Mycobacterium tuberculosis (Mtb) is the single leading cause of death from a bacterial pathogen and estimated to be the leading cause of death from AMR. A pyrido-benzimidazole, 14, was reported to have potent bactericidal activity against Mtb. Here, we isolated multiple Mtb clones resistant to 14. Each had mutations in the putative DNA-binding and dimerization domains of rv2887, a gene encoding a transcriptional repressor of the MarR family. The mutations in Rv2887 led to markedly increased expression of rv0560c. We characterized Rv0560c as an S-adenosyl-L-methionine-dependent methyltransferase that N-methylates 14, abolishing its mycobactericidal activity. An Mtb strain lacking rv0560c became resistant to 14 by mutating decaprenylphosphoryl-β-d-ribose 2-oxidase (DprE1), an essential enzyme in arabinogalactan synthesis; 14 proved to be a nanomolar inhibitor of DprE1, and methylation of 14 by Rv0560c abrogated this activity. Thus, 14 joins a growing list of DprE1 inhibitors that are potently mycobactericidal. Bacterial methylation of an antibacterial agent, 14, catalyzed by Rv0560c of Mtb, is a previously unreported mechanism of AMR

Structural brain correlates of childhood inhibited temperament: an ENIGMA-Anxiety Mega-analysis

NWORubicon 019.201SG.022Pathways through Adolescenc

Tracking System : Suaineadh satellite experiment

The purpose of this bachelor thesis is to present a tracking system for the Suaineadh satellite experiment. The experiment is a part of the REXUS (Rocket EXperiments for University Students) program and the objective is to deploy a foldable web in space. The assignment of this thesis is to develop a tracking system to find the parts from the Suaineadh experiment that will land on Earth. It is important to find the parts and recover all the data that the experiment performed during the travel in space. The implementation of this thesis investigates two different ways to track and find the experiment. The first way is to locate the experiment module by a Global Positioning System (GPS) and send the coordinates to a satellite modem, controlled by a programmed microprocessor. The other way is by using a radio beacon that sends a speciffic radio frequency. The results of this thesis presents a prototype for the tracking system with a GPS and the satellite modem and code example for the microprocessor. It also presents a working radio freqency beacon system on a Printed Circuit Board. The thesis had some unexpected incidents and had to change some directives. This rendered the work to take longer time then estimated. Despite the difficulties resulted this thesis in a working system to track the experiment

Tracking System : Suaineadh satellite experiment

The purpose of this bachelor thesis is to present a tracking system for the Suaineadh satellite experiment. The experiment is a part of the REXUS (Rocket EXperiments for University Students) program and the objective is to deploy a foldable web in space. The assignment of this thesis is to develop a tracking system to find the parts from the Suaineadh experiment that will land on Earth. It is important to find the parts and recover all the data that the experiment performed during the travel in space. The implementation of this thesis investigates two different ways to track and find the experiment. The first way is to locate the experiment module by a Global Positioning System (GPS) and send the coordinates to a satellite modem, controlled by a programmed microprocessor. The other way is by using a radio beacon that sends a speciffic radio frequency. The results of this thesis presents a prototype for the tracking system with a GPS and the satellite modem and code example for the microprocessor. It also presents a working radio freqency beacon system on a Printed Circuit Board. The thesis had some unexpected incidents and had to change some directives. This rendered the work to take longer time then estimated. Despite the difficulties resulted this thesis in a working system to track the experiment

Personalized Environmental Policy : A personal guide towards sustainable environmental decisions

Syftet med detta projekt var att skapa underlaget till ett personligt digitalt verktyg. Verktyget, som är menat att vara en applikation till smarttelefoner, ska hjälpa den enskilde individen att minska sin negativa inverkan på miljön. Detta ska skegenom att appen hjälper individen att hitta ett mer hållbart sätt att leva. Detta genom att både informera användaren om vad den vardagliga konsumtionen orsakarsamt hitta alternativ till dagens levnadssätt. Det beslutsfattande elementet iverktyget skulle bygga på en metod som är framtagen av Joakim Karlsson. Denna metod går ut på att presentera alternativ parvis för användaren och genom attvikta alternativen sortera ut överflödiga jämförelser.För att kunna presentera klimatsmarta alternativ för användaren behövdes en databas med statistik på utsläpp som produkter orsakar inom alla konsumtionområden. En litteraturstudie utfördes där möjligheterna till att bygga en sådan databas undersöktes. Konsumtionsmönster undersöktes som skulle möjliggöra en miljömässigt hållbar levnadsstandard. Vidare studerades motivationsmetoder som, genom att föras in i appen, skulle bidra till att fler individer lyckas genomgå en förändring. Slutligen sammanställdes en simulering av appen och möjliga vägar för att kommersialisera produkten utvärderades. Nedan följer en lista av kortfattade slutsatser och resultat. • Att basera appens beslutsprocess på Joachim Karlssons metod fungerar ochär lämplig att integrera i en app som är anpassad för en individ. • En databas som innehåller statistik för utsläpp av produkter är teoretisktmöjligt att bygga, men alldeles för tidskrävande i detta projekt. 15 datapunkter samlades istället in för att simulera funktionen. • De tekniker och teorier som studerats inom motivationsmetoder har lett tillen diskussion kring hur dessa kan implementeras i appen. • Marknadsanalysen synliggjorde företaget Svalna som utvecklat en liknande app. Efter ett möte där de visade intresse för underlaget som utvecklats idenna studie övervägdes de olika vägarna för att kommersialisera underlaget. Slutsatsen som drogs var att det bästa alternativet för fortsatt arbete är ettsamarbete med Svalna.The purpose of this project was to lay the foundations for a personal digital tool.The tool, which is intended to be an application for smartphones, will be designed to help individuals reduce their negative impact on the environment. This will be achieved by helping the individual find a more sustainable lifestyle through the app. The app will inform the user about the impact on the climate from daily consumption and thereafter suggest possible changes to their current lifestyle. The decision-making element in the tool would be based on a method that aims to streamline decision making in companies through pairwise comparisons. This is achieved by weighting the categories and then presenting them in pairs to the user. To present the user with environmentally friendly alternative ways to live, a broad database of statistics on emissions caused by the consumption of products was needed. A literature study was conducted to find out if such a database would be possible to build. Furthermore, studies where conducted to find the consumption patterns of an environmentally sustainable lifestyle. To get as many people to succeed in changing their lifestyle as possible, theories and methods regarding motivation were studied. Finally, a simulation of the app was compiled and possible ways to commercialize the product were evaluated. The list below briefly covers the conclusions and results of the project. • It is possible to integrate Joachim Karlsson’s method in an app of which targets the individual. • The database containing statistics on emissions is theoretically viable but too time-consuming to be a part of this project. 15 data points were collected to be able to simulate the function of the app. • The techniques and theories behind the motivational methods have led to a discussion of how these methods can be implemented in the app. • The market analysis drew attention to a company named Svalna who made an app with a similar purpose. After a meeting, where they showed interest in this concept, possible ways to commercialize the app were considered. Finally, it was concluded that the best option forward is a collaboration with Svalna