Effect of flavonoids on 2 `-deoxyguanosine and DNA oxidation caused by singlet molecular oxygen

Antioxidant potential is generally investigated by assaying the ability of a compound to protect biological systems from free radicals. However, non-radical reactive oxygen species can also be harmful. Singlet molecular oxygen ((1)O(2)) is generated by energy transfer to molecular oxygen. The resulting (1)O(2) is able to oxidize the nucleoside 2`-deoxyguanosine (dGuo), which leads to the formation of 8-oxo-7,8-dihydro-2`-deoxyguanosine (8-oxodGuo) and spiroiminodihydantoin 2`-deoxyribonucleoside diastereomers (dSp) in an aqueous solution. The main objective of the present study was to verify whether the presence of flavonoids (flavone, apigenin, quercetin, morin and catechin) at different concentrations could protect dGuo from (1)O(2) damage. Of the tested flavonoids, flavone possessed antioxidant activity, as determined by a decrease in the formation of both products. Apigenin, morin, quercetin and catechin all increased the formation of 8-oxodGuo at a concentration of 100 mu M. The quantification of plasmid strand breaks after treatment with formamidopyrimidine-DNA glycosylase showed that flavone protected and quercetin and catechin enhanced DNA oxidation. Our results show that compounds, such as flavonoids, may affect the product distribution of (1)O(2)-mediated oxidation of dGuo, and, in particular, high concentrations of flavonoids with hydroxyl groups in their structure lead to an increase in the formation of the mutagenic lesion 8-oxodGuo. (C) 2010 Elsevier Ltd. All rights reserved.

Ultrasensitive Simultaneous Quantification of 1,N(2)-Etheno-2 `-deoxyguanosine and 1,N(2-)Propano-2 `-deoxyguanosine in DNA by an Online Liquid Chromatography-Electrospray Tandem Mass Spectrometry Assay

Exocyclic DNA adducts produced by exogenous and endogenous compounds are emerging as potential tools to study a variety of human diseases and air pollution exposure. A highly sensitive method involving online reverse-phase high performance liquid chromatography with electrospray tandem mass spectrometry detection in the multiple reaction monitoring mode and employing stable isotope-labeled internal standards was developed for the simultaneous quantification of 1,N(2)-etheno-2`-deoxyguanosine (1,N(2)-epsilon dGuo) and 1,N(2)-propano-2`-deoxyguanosine (1,N(2)-propanodGuo) in DNA. This methodology permits direct online quantification of 2`-deoxyguanosine and ca. 500 amol of adducts in 100 mu g of hydrolyzed DNA M the same analysis. Using the newly developed technique, accurate determinations of 1,N(2)-etheno-2`-deoxyguanosine and 1,N2-propano-2`-deoxyguanosine levels in DNA extracts of human cultured cells (4.01 +/- 0.32 1,N(2)-epsilon dGuo/10(8) dGuo and 3.43 +/- 0.33 1,N(2)-propanodGuo/10(8) dGuo) and rat tissue (liver, 2.47 +/- 0.61 1,N(2)-epsilon dGuo/10(8) dGuo and 4.61 +/- 0.69 1,N(2)-propanodGuo/108 dGuo; brain, 2.96 +/- 1.43,N(2)-epsilon dGuo/10(8) dGuo and 5.66 +/- 3.70 1,N(2)-propanoclGuo/10(8) dGuo; and lung, 0,87 +/- 0.34 1,N(2)-edGuo/ 10(8) dGuo and 2.25 +/- 1.72 1,N(2)-propanodGuo/10(8) dGuo) were performed. The method described herein can be used to study the biological significance of exocyclic DNA adducts through the quantification of different adducts in humans and experimental an with pathological conditions and after air pollution exposure.

Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multifactorial and remain unclear. Here we examined DNA damage;p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93) --> Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2`-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This toxic activity of mutant SOD1 in the nucleus may play an important role in the complex mechanisms associated with motor neuron death observed in ALS pathogenesis. (C) 2010 Elsevier B.V. All rights reserved.

Single-wall carbon nanotubes modified with organic dyes: Synthesis, characterization and potential cytotoxic effects

This work deals with the covalent functionalization of single-wall carbon nanotubes (SWNTs) with phenosafranine (PS) and Nile Blue (NB) dyes. These dyes can act as photosensitizers in energy and electron transfer reactions, with a potential to be applied in photodynamic therapy. Several changes in the characteristic Raman vibrational features of the dyes suggest that a covalent modification of the nanotubes with the organic dyes occurs. Specifically, the vibrational modes assigned to the NH(2) moieties of the dyes are seen to disappear in the SWNT-dye nanocomposites, corroborating the bond formation between amine groups in the dyes and carboxyl groups in the oxidized nanotubes. The X-ray absorption (XANES) data also show, that the intense band at 398.6 eV attributed to 1s -> 2p pi* transition of the nitrogen of the aromatic PS ring, is shifted due to the bonding with the carbonic structure of the SWNTs. The cytotoxicity data of dyes-modified SWNT composites in the presence and absence of light shows that the SWNT-NB (4 mu g/mL) composite presents a good photodynamic effect, namely a low toxicity in the dark, higher toxicity in the presence of light and also a reduced dye photobleaching by auto-oxidation. (C) 2010 Elsevier B.V. All rights reserved.

Mechanistic study of the addition reaction of TeCl(4) to alkynes: Participation of TeCl(3) centered-radical

The mechanism of the addition reaction of TeCl(4) to alkynes was indirectly established by the detection of TeCl(3) centered radicals using EPR spin trapping, ESI-MS and ESI-MS/MS characterization. Crown Copyright (C) 2008 Published by Elsevier B. V. All rights reserved.

På systrars initiativ : Dalarnes sjuksköterskeförening 1920-1933

Denna uppsats dokumenterar uppkomst, frontpersoner och verksamhet för Dalarnes sjuksköterskeförening (DSF) mellan åren 1920-1933, vilket är en lokal sjuksköterskeförening som senare blev underavdelning till riksföreningen Svensk sjuksköterskeförening (SSF). DSF var den första lokala sjuksköterskeföreningen och startades 1920 av sjuksköterskor kring området Falun/Borlänge. Det var inte en elitförening likt SSF som i sin professionalisering enbart ville avskärma sig från de underordnade som biträden och kämpa för status och kalltanken. DSF var en förening som ville stärka kårandan men även arbeta för löne- och arbetsförhållandefrågor, vilket på den tiden egentligen hörde samman med socialistiska föreningar. I sin verksamhet ville de även få till stånd en platsbyrå för föreningens medlemmar. Det var en politiskt oberoende förening som arbetade fackligt. År 1933 blev Dalarnes sjuksköterskeförening en underavdelning till SSF som från och med det året började arbeta fackligt på lokalföreningars begäran.

Class Struggle, Elitism and Social Collectivism in Ngugi wa Thiong’o’s Devil on the Cross : A Marxist Approach

Ngugi wa Thiong’o’s Devil on the Cross represents both an insightful interpretation and a scathing critique of Kenyan politics and society during the period of neo-colonialism. The present thesis aims to explore, with the help of Marxist ideology and criticism, the relevance of the issues of class struggle, elitism and social collectivism in the novel. At the same time, this study will attempt to define Devil on the Cross as a "national allegory" depicting situations that are common to almost all post-colonial societies, and in particular, how the novel's ideological and political commitment is an important feature as it reflects Ngugi’s effort to draw attention to how Kenya and Africa as a whole suffered from imperialism, neo-colonialism, and a corrupt and greedy capitalist society.

Är den tillämpade idrottsforskningen könsneutral? : Fallstudie på en tidskrifts publikationer

Syfte Mötet mellan kroppen som något socialt format och som något biologiskt mätbart som sker i idrott kan vara problematiskt vilket visat sig genom tidigare forskning inom området. Olika sätt att se på kön kan göra att biologisk jämlikhet mellan män och kvinnor förutsätts där det finns skillnader eller att skillnader förutsätts där det inte finns några. Syftet med denna studie var att genom en systematisk litteraturgranskning belysa det tillämpade idrottsvetenskapliga forskningsfältets urval av försökspersoner och rapportering av dessa. Samt utifrån teorier kring kön och genus tolka resultatet av detta. Vidare var syftet att undersöka effekten av förstaförfattarens könskategori på val av urvalsgrupper och rapportering av dessa. Studien tar bland annat sin utgångspunkt i Hirdmans formler för förhållandet mellan man och kvinna för att analysera de resultat som fås. Tas både kulturella och biologiska aspekter på kroppen i beaktning i den idrottsvetenskapliga forskning som sker som sedan skall tillämpas i praktiken? Metod Genom en fallstudie av en idrottsvetenskaplig tidskrift som publicerar studier inom den tillämpade idrottsvetenskapliga forskningen kodades dess publicerade artiklar. Totalt kodades 291 artiklar som hörde till original investigations, case studies och technical reports. Särskild vikt lades vid de kodade artiklarnas sammanfattning och urval av försökspersoner varför titel, sammanfattning, sökord och könskategori på förstaförfattare kodades. Även könsfördelning på försökspersonerna i urvalsgruppen och totalt antal försökspersoner kodades.  Resultat I häften av alla artiklar gick könsfördelning inte att utläsa i sammanfattning. Totalt identifierades 8643 försökspersoner varav 4191 var av manligt kön, 1440 av kvinnligt kön och 3012 gick inte att koda till en könskategori. Fler än 50 % av artiklarna identifierades med ett urval av enbart män, 6 % med ett urval av enbart kvinnor, 21 % blandat urval och resterande gick inte att koda. I 84 % av fallen identifierades förstaförfattare som man. Slutsats Vid en första anblick av en artikel kan det vara svårt att bilda sig en uppfattning kring könsfördelning på studiens urvalsgrupp. Urvalsgrupperna är inte jämnt fördelade mellan kvinnor och män. En skev rekrytering av urvalet kan ge upphov till att den idrottsvetenskapliga forskningen speglar idrottens premisser att det är en manlig arena. På detta sätt riskerar den att reproducera den manliga normen inom idrotten genom att påverka framtida forskning eller idrottsutbildningar.

Designing Agent-Oriented Systems by Analysing Agent Interactions

We propose a preliminary methodology for agent-oriented software engineering based on the idea of agent interaction analysis. This approach uses interactions between undetermined agents as the primary component of analysis and design. Agents as a basis for software engineering are useful because they provide a powerful and intuitive abstraction which can increase the comprehensiblity of a complex design. The paper describes a process by which the designer can derive the interactions that can occur in a system satisfying the given requirements and use them to design the structure of an agent-based system, including the identification of the agents themselves. We suggest that this approach has the flexibility necessary to provide agent-oriented designs for open and complex applications, and has value for future maintenance and extension of these systems.

Towards a Methodology for Coordination Mechanism Selection in Open Systems

Agent-oriented software engineering (AOSE) is a promising approach to developing applications for dynamic open systems. If well developed, these applications can be opportunistic, taking advantage of services implemented by other developers at appropriate times. However, methodologies are needed to aid the development of systems that are both flexible enough to be opportunistic and tightly defined by the application requirements. In this paper, we investigate how developers can choose the coordination mechanisms of agents so that the agents will best fulfil application requirements in an open system.