1,413 research outputs found
The pathway to pyrimidines : The essential focus on dihydroorotate dehydrogenase, the mitochondrial enzyme coupled to the respiratory chain
No full textThis paper is based on the Anne Simmonds Memorial Lecture, given by Monika Löffler at the International Symposium on Purine and Pyrimidine Metabolism in Man, Lyon 2019. It is dedicated to H. Anne Simmonds (died 2010) - a founding member of the ESSPPMM, since 2003 Purine and Pyrimidine Society - and her outstanding contributions to the identification and study of inborn errors of purine and pyrimidine metabolism. The distinctive intracellular arrangement of pyrimidine de novo synthesis in higher eukaryotes is important to cells with a high demand for nucleic acid synthesis. The proximity of the enzyme active sites and the resulting channeling in CAD and UMP synthase is of kinetic benefit. The intervening enzyme dihydroorotate dehydrogenase (DHODH) is located in the mitochondrion with access to the ubiquinone pool, thus ensuring efficient removal of redox equivalents through the constitutive activity of the respiratory chain, also a mechanism through which the input of 2 ATP for carbamylphosphate synthesis is balanced by Oxphos. The obligatory contribution of O2 to de novo UMP synthesis means that DHODH has a pivotal role in adapting the proliferative capacity of cells to different conditions of oxygenation, such as hypoxia in growing tumors. DHODH also is a validated drug target in inflammatory diseases. This survey of selected topics of personal interest and reflection spans some 40 years of our studies from tumor cell cultures under hypoxia to in vitro assays including purification from mitochondria, localization, cloning, expression, biochemical characterization, crystallisation, kinetics and inhibition patterns of eukaryotic DHODH enzymes
Genetic basis of haemolytic anemia caused by pyrimidine 5’nucleotidase deficiency.
No full textPyrimidine 5' nucleotidase (P5'N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Recently, a protein with P5'N-1 activity was analyzed and a provisional complementary DNA (cDNA) sequence published. This sequence was used to study 3 families with P5'N-1 deficiency. This approach generated a genomic DNA sequence that was used to search GenBank and identify the gene for P5'N-1. It is found on chromosome 7, consists of 10 exons with alternative splicing of exon 2, and produces proteins 286 and 297 amino acids long. Three homozygous mutations were identified in this gene in 4 subjects with P5'N-1 deficiency: codon 98 GATGTT, AspVal (linked to a silent polymorphism codon 92, TACTAT), codon 177, CAATAA, Glntermination, and IVS9-1, GT. The latter mutation results in the loss of exon 9 (201 bp) from the cDNA. None of these mutations was found in 100 normal controls. The DNA analysis was complicated by P5'N-1 pseudogenes found on chromosomes 4 and 7. This study is the first description of the structure and location of the P5'N-1 gene, and 3 mutations have been identified in affected patients from separate kindreds
Diagnosis and Treatment of Inborn Errors of Purine and Pyrimidine Metabolism: An Overview
No full textAutonomy and Advocacy in Perinatal Nursing Practice
No full textAdvocacy has been positioned as an ideal within the practice of nursing, with national guidelines and professional standards obliging nurses to respect patients' autonomous choices and to act as their advocates. However, the meaning of advocacy and autonomy is not well defined or understood, leading to uncertainty regarding what is required, expected and feasible for nurses in clinical practice. In this article, a feminist ethics perspective is used to examine how moral responsibilities are enacted in the perinatal nurse-patient relationship and to explore the interaction between the various threads that influence, and are in turn affected by, this relationship. This perspective allows for consideration of contextual and relational factors that impact on the way perinatal nursing care is given and received, and provides a framework for exploring the ways in which patient autonomy, advocacy and choice are experienced by childbearing women and their nurses during labour and birth
Was English Good for Us?
No full textThe following report investigates the effects studying in a multilingual study environment has up-on students. The foundation of this case is built on interviews with four RUC alumni, as we will investigate how their experiences has influenced their lives. The interviews are based on the methodology described in Steinar Kvale and Svend Brinkmann's book ‘InterViews’, to ensure the utmost satisfactory results. The data we collected through the interview process was hereafter analysed according to two theories: Pierre Bourdieu's Capital Theory and Robert Philipson's Theo-ry of Linguistic Imperialism. This project is relevant as the world is moving towards a more interconnected, globalised world-structure and ergo a study into these affairs would be appropriate to be able to navigate in and fully comprehend such a phenomenon.The following report investigates the effects studying in a multilingual study environment has up-on students. The foundation of this case is built on interviews with four RUC alumni, as we will investigate how their experiences has influenced their lives. The interviews are based on the methodology described in Steinar Kvale and Svend Brinkmann's book ‘InterViews’, to ensure the utmost satisfactory results. The data we collected through the interview process was hereafter analysed according to two theories: Pierre Bourdieu's Capital Theory and Robert Philipson's Theo-ry of Linguistic Imperialism. This project is relevant as the world is moving towards a more interconnected, globalised world-structure and ergo a study into these affairs would be appropriate to be able to navigate in and fully comprehend such a phenomenon
A Quantitative Study of Attitudes towards Varieties of English in Denmark
No full textI dette projekt undersøges engelsktalende danskeres sprogattituder angående forskellige former for engelsk. Undersøgelsen udspringer af en fælles interesse for sprogattituder, samt ideen om at nye sprogattituder er ved at forme sig i kraft af stigende globalisering, nationalismens genkomst, samt et vedvarende og tiltagende engelsk sprogbrug i Danmark. Problemformulering lyder således: Hvilke fremkomne attituder i forhold til forskellige former for engelsk findes der i Danmark, og hvad siger disse om stereotyper angående overlegenhed, attraktion og dynamik i engelsk kommunikation? Ud over en række underspørgsmål, arbejdes der yderligere med hypotesen om at den tiltagende nationalisme (ind- så vel som udenlands) muligvis har medvirket til at gøre den danske variant af engelsk mere accepteret, eller måske endda foretrukket. Teoriafsnittet indeholder teoretisk begrebsafklaring, samt gennemgange af teoretiske emner som Standardisering i Sprog, Attituder i forhold til Sprogvariation, baseret på udvalgte værker af forskere som Jennifer Jenkins og Peter Garrett, blandt andre. Metodisk valgtes en kvantitativ tilgang. Dette i form af en spørgeskemaundersøgelse med spørgsmål baseret på skalaer der skulle belyse de spurgtes holdninger i forhold til parametrene overlegenhed, attraktion og dynamik. Ud over at fastslå data som alder, køn og så videre, drejer spørgsmålene sig om i hvilken grad de forskellige varianter af engelsk egner sig som togannoncører. Disse valgte varianter var tre indfødte: Received Pronunciation, General American og skotsk engelsk, samt tre ikke-indfødte varianter: tanzanisk engelsk, indisk engelsk og dansk engelsk. Spørgeskemaet blev udleveret via sociale medier, samt gennem personlige kontakter blandt stab på enkelte gymnasier. Dette gav et samlet antal på 54 svarsæt, hvoraf to tredjedele var 15-20 år gamle, og den sidste tredjedel over 40. Resultaterne af analysen af de adspurgtes svar viste en positive rangering af dansk engelsk. Blandt den ældre gruppe var RP den fortrukne variant, mens DE fik en anden plads på alle spørgsmål. Modsat var den yngre gruppe mere begejstret for GA end RP, hvor DE ligeledes lå umiddelbart efter favoritten. Tanzanisk og indisk engelsk var ikke agtet særligt højt. Disse resultater ledte til en diskussion om sprogattituder og sprogbrug i Danmark, samt stereotype anskuelser af bestemte varianter af engelsk. Den overordnede konklusion lyder på at specifikke stereotyper var at spore i svarene, især i forhold til indisk og skotsk engelsk, samt RP. Både GA og RP var vurderet langt mere positivt end tanzanisk og indisk engelsk (og skotsk, på de fleste spørgsmål). I lyset af at dansk engelsk var den højest vurderet generelt, kan det formodes at denne variant er ved at blive mere accepteret i Danmark.This project investigates language attitudes toward varieties of native and non-native English among Danes in Denmark. The investigation derives from a common interest in language attitudes, but also from the fact that increasing globalisation, the (re)emergence of nationalism, and a continuing and increasing use of English in Denmark, may have led to new language attitudes being formed. The leading question has been, “What are the emerging attitudes towards native and nonnative varieties of English in Denmark and what do they reveal about stereotypes pertaining to superiority, attractiveness and dynamism for communication in English?”. In addition to a number of research questions, a hypothesis has been put forward that given the increased interest in national identity (in Denmark, but also abroad), the Danish variety of English may have become more respected, or has even earned prestige. The theory section contains descriptions of terminology and an outline of theories such as Standardisation in Language and Attitudes Towards Language Variation, based on selected works by Jennifer Jenkins and Peter Garrett, among others. Methodologically, we chose a quantitative approach. More specifically, a survey with questions based on the semantic differential scales of superiority, attractiveness and dynamism. The selected varieties were three native Englishes: Received Pronunciation, General American and Scottish English, and three non-native varieties: Tanzanian English, Indian English and Danish English. The survey was distributed via social media, as well as through personal contacts at Danish high schools. This gave us a final count of 54 respondents; two thirds were young people between ages 15 and 20, and one third were above forty years of age. The results of the analyses pointed to a positive rating of Danish English. Among the older group, RP was the favoured native variety, while DE was rated in second place on all questions. In the younger group, however, GA was the favoured native variety, while only DE rated higher. The non-native varieties of Tanzanian and Indian English were both rated rather poorly. These results lead to a discussion of the changing landscape of English language use and attitude in Denmark, as well as stereotypes pertaining to the selected varieties of English. The overall conclusion of the project, was that certain stereotypes were prevalent, especially in regard to Indian and Scottish English, as well as RP. The native varieties of GA and RP were rated far above Tanzanian and Indian English (as well as Scottish English on most scales). Considering Danish English was rated overall most favourably, it stands to reason this variety is seeing a rise in acceptance in Denmark
87 NAD SYNTHESIS BY ERYTHROCYTES IN PHOSPHORIBOSYL -PYROPHOSPHATE SYNTHETASE (PPRPs) SUPERACTIVITY
No full textNAD Synthesis by Erythrocytes in Phosphoribosylpyrophosphate Synthetase (PRPPs) Superactivity
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