scholarly journals NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Angel L. Pey ◽  
Clare F. Megarity ◽  
David J. Timson
Keyword(s):  
Active Sites ◽  
Physiological Role ◽  
Polymorphic Form ◽  
Normal Function ◽  
Enzyme Mechanism ◽  
Quinone Oxidoreductase ◽  
Lower Stability ◽  
Increased Risk ◽  
Wide Range ◽  
The Right

AbstractNAD(P)H quinone oxidoreductase 1 (NQO1) catalyses the two electron reduction of quinones and a wide range of other organic compounds. Its physiological role is believed to be partly the reduction of free radical load in cells and the detoxification of xenobiotics. It also has non-enzymatic functions stabilising a number of cellular regulators including p53. Functionally, NQO1 is a homodimer with two active sites formed from residues from both polypeptide chains. Catalysis proceeds via a substituted enzyme mechanism involving a tightly bound FAD cofactor. Dicoumarol and some structurally related compounds act as competitive inhibitors of NQO1. There is some evidence for negative cooperativity in quinine oxidoreductases which is most likely to be mediated at least in part by alterations to the mobility of the protein. Human NQO1 is implicated in cancer. It is often over-expressed in cancer cells and as such is considered as a possible drug target. Interestingly, a common polymorphic form of human NQO1, p.P187S, is associated with an increased risk of several forms of cancer. This variant has much lower activity than the wild-type, primarily due to its substantially reduced affinity for FAD which results from lower stability. This lower stability results from inappropriate mobility of key parts of the protein. Thus, NQO1 relies on correct mobility for normal function, but inappropriate mobility results in dysfunction and may cause disease.

scholarly journals A Systematic Review of Serum γ-Glutamyltransferase as a Prognostic Biomarker in Patients with Genitourinary Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 549
Author(s):  
Kosuke Takemura ◽  
Philip G. Board ◽  
Fumitaka Koga
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Cancer Cells ◽  
Elevated Serum ◽  
Physiological Role ◽  
Epidemiological Studies ◽  
Genitourinary Cancer ◽  
Increased Risk ◽  
Wide Range

γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells against oxidative stress. GGT has been proposed as a biomarker of carcinogenesis and tumor progression given that GGT activity is important during both the promotion and invasion phases in cancer cells. Moreover, GGT expression is reportedly related to drug-resistance possibly because a wide range of drugs are conjugated with GSH, the availability of which is influenced by GGT activity. While serum GGT activity is commonly used as a quick, inexpensive, yet reliable means of assessing liver function, recent epidemiological studies have shown that it may also be an indicator of an increased risk of prostate cancer development. Moreover, elevated serum GGT is reportedly an adverse prognostic predictor in patients with urologic neoplasms, including renal cell carcinoma, prostate cancer, and urothelial carcinoma, although the background mechanisms have still not been well-characterized. The present review article summarizes the possible role of GGT in cancer cells and focuses on evidence evaluation through a systematic review of the latest literature on the prognostic role of serum GGT in patients with genitourinary cancer.

Functional Polymorphisms in Oxidant Metabolism and DNA Repair Pathways and Risk of Leukemia and Transient Myeloproliferative Disorder in Children with Down Syndrome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2947-2947
Author(s):  
Melissa S Rayburg ◽  
Mi-Ok Kim ◽  
Todd Alonzo ◽  
Robert Gerbing ◽  
Gretchen A Radloff ◽  
...  
Keyword(s):  
Dna Repair ◽  
Down Syndrome ◽  
Myeloproliferative Disorder ◽  
Healthy Controls ◽  
Quinone Oxidoreductase ◽  
Children With Down Syndrome ◽  
Transient Myeloproliferative Disorder ◽  
Functional Polymorphisms ◽  
Increased Risk ◽  
Wide Range

Abstract Children with Down syndrome can have a wide range of developmental abnormalities related to the presence of additional genetic material from a small region of chromosome 21. Additional copies of the Cu/Zn superoxide dismutase gene and related genes at this locus are believed to contribute to high oxidative stress, and increased endogenous DNA damage and deficient repair observed in cells from patients with Down syndrome. Children with Down syndrome also have a markedly increased risk for the development of serious hematological disorders, including an approximately 20-fold increased risk for the development of acute myeloid leukemia (AML). In addition, in early infancy, as many as 10% may develop a transient myeloproliferative disorder (TMD). The basis for this overall increased risk is unknown, as are the risk factors influencing which specific patients with Down syndrome develop AML/TMD. We sought to test the hypothesis that functional polymorphisms in genes involved in oxidant metabolism and DNA repair contribute to the increased risk of AML and TMD in children with Down syndrome. We studied functional polymorphisms in the oxidant metabolizing enzyme NADPH quinone oxidoreductase 1 (NQO1), and in the DNA repair proteins X-ray repair cross complementing 1 protein (XRCC1) and Fanconi anemia complementation group A protein (FANCA). Genotyping was conducted in 170 patients with Down syndrome AML or TMD, and 202 healthy blood donor controls. All genotype frequencies in the control populations were consistent with those expected from Hardy-Weinberg equilibrium. We found that the variant NQO1 Pro187Ser allele, associated with reduced quinone reductase activity, occurred with a greater frequency in the Down syndrome AML/TMD patient population compared to healthy controls (OR, 1.61; 95% CI, 1.067–2.426; p=0.0231). The FANCA-1501 variant allele frequency was observed more frequently in Down syndrome AML/TMD patients compared to healthy controls (OR, 1.77; 95%CI, 1.220–2.568; p=0.0025). The variant XRCC-1 Arg399Gln allele was observed less frequently in the TMD/DS AML population as compared to controls (OR, 0.536; CI, 0.354–0.811; p=0.0031). These latter findings parallel the observation of a protective effect against AML in non-Down syndrome individuals with at least one copy of the XRCC-1 Arg399Gln allele (Seedhouse et al. Blood2002, 100:3761). Conclusion: These preliminary studies, representing the only reported data in Down Syndrome TMD/AML patients, suggest that functional polymorphic variants of the NQO1, FANCA, and XRCC1 genes involved in oxidant metabolism and DNA repair may influence the risk for developing leukemia. Studies involving future cohorts will be needed to confirm these observations.

scholarly journals Kinetic studies of the acylation of pig muscle–d-glyceraldehyde 3-phosphate dehydrogenase by 1,3-diphosphoglycerate and of proton uptake and release in the overall enzyme mechanism

1973 ◽  
Vol 135 (4) ◽  
pp. 695-703 ◽  
Author(s):  
P. J. Harrigan ◽  
D. R. Trentham
Keyword(s):  
Ionic Strength ◽  
Active Sites ◽  
Salt Effect ◽  
Kinetic Studies ◽  
Enzyme Mechanism ◽  
Binary Complex ◽  
Wide Range ◽  
Pig Muscle ◽  
Proton Uptake ◽  
Ph Range

In the presence of NAD+the acylation by 1,3-diphosphoglycerate of the four active sites of pig muscle d-glyceraldehyde 3-phosphate dehydrogenase can be monitored at 365nm by the disappearance of the absorption band present in the binary complex of NAD+and the enzyme. A non-specific salt effect decreased the acylation rate 25-fold when the ionic strength was increased from 0.10 to 1.0. This caused acylation to be the rate-limiting process in the enzyme-catalysed reductive dephosphorylation of 1,3-diphosphoglycerate at high ionic strength at pH8. The salt effect permitted investigation of the acylation over a wide range of conditions. Variation of pH from 5.4 to 8.6 produced at most a two-fold change in the acylation rate. One proton was taken up per site acylated at pH8.0. By using a chromophoric H+indicator the rate of proton uptake could be monitored during the acylation and was also almost invariant in the pH range 5.5–8.5. Transient kinetic studies of the overall enzyme-catalysed reaction indicated that acylation was the process involving proton uptake at pH8.0. The enzyme mechanism is discussed in the light of these results.

Port in oncology practice: 3-monthly locking with normal saline for catheter maintenance, a preliminary report

2017 ◽  
Vol 18 (4) ◽  
pp. 325-327 ◽  
Author(s):  
Gianfranca Solinas ◽  
Francesca Platini ◽  
Maurizio Trivellato ◽  
Carla Rigo ◽  
Oscar Alabiso ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Normal Saline ◽  
Venous Access ◽  
Central Venous ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Wide Range ◽  
Oncology Practice ◽  
The Right

Introduction Patients with cancer need stable venous access using central vascular devices like central venous ports and peripherally inserted central catheters that can be used for a wide range of indications. Numerous flushing protocols exist including different frequencies for catheter locking to maintain catheter patency. The aim of this retrospective study was to evaluate the incidence of lumen occlusion of central venous ports in a group of adult cancer patients, adopting a policy of locking with normal saline every three months. Methods This is a single-center retrospective observational study. During follow-up, we analyzed adult cancer patients who had undergone port insertion from January 1st, 2007 to August 31st, 2014. Flushing and locking were performed every three months with a syringe containing normal saline. Results We collected data from 381 patients with ports inserted in subclavian vein (379 patients) and in the right jugular vein (2 patients). Locking was performed during 3-monthly follow-up visits. Median follow-up was 810 days (90-2700 days). Among 381 ports, 59 were removed; the reasons for removal were: end of use (45 cases), catheter rupture (9 cases), dislocation (3 cases) and catheter-related bloodstream infection (2 cases). We had no reports of lumen occlusion. Conclusions Our data suggest that locking ports with normal saline every three months is not associated with an increased risk of lumen occlusion.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

It is better an approximate answer to the right question than the exact answer to the wrong question : the case of the psychometric analysis of the ASQ:SE

2020 ◽  
Author(s):  
Luis Anunciacao ◽  
janet squires ◽  
J. Landeira-Fernandez
Keyword(s):  
Internal Structure ◽  
Statistical Methods ◽  
Principal Component ◽  
Psychological Theory ◽  
Published Data ◽  
Multivariate Statistical ◽  
Exact Answer ◽  
Wide Range ◽  
Ages And Stages Questionnaire ◽  
The Right

One of the main activities in psychometrics is to analyze the internal structure of a test. Multivariate statistical methods, including Exploratory Factor analysis (EFA) and Principal Component Analysis (PCA) are frequently used to do this, but the growth of Network Analysis (NA) places this method as a promising candidate. The results obtained by these methods are of valuable interest, as they not only produce evidence to explore if the test is measuring its intended construct, but also to deal with the substantive theory that motivated the test development. However, these different statistical methods come up with different answers, providing the basis for different analytical and theoretical strategies when one needs to choose a solution. In this study, we took advantage of a large volume of published data (n = 22,331) obtained by the Ages and Stages Questionnaire Social-Emotional (ASQ:SE), and formed a subset of 500 children to present and discuss alternative psychometric solutions to its internal structure, and also to its subjacent theory. The analyses were based on a polychoric matrix, the number of factors to retain followed several well-known rules of thumb, and a wide range of exploratory methods was fitted to the data, including EFA, PCA, and NA. The statistical outcomes were divergent, varying from 1 to 6 domains, allowing a flexible interpretation of the results. We argue that the use of statistical methods in the absence of a well-grounded psychological theory has limited applications, despite its appeal. All data and codes are available at https://osf.io/z6gwv/.

THE VALUE OF LOVE IN THE SYSTEM OF FORMATION OF THE PROFESSIONAL MATURITY OF THE EDUCATOR

2020 ◽  
Vol 1 (10(79)) ◽  
pp. 12-18
Author(s):  
G. Bubyreva
Keyword(s):  
Russian Federation ◽  
The State ◽  
Educational Process ◽  
Wide Range ◽  
The Family ◽  
The Russian Federation ◽  
The Government ◽  
The Individual ◽  
The Right

The existing legislation determines the education as "an integral and focused process of teaching and upbringing, which represents a socially important value and shall be implemented so as to meet the interests of the individual, the family, the society and the state". However, even in this part, the meaning of the notion ‘socially significant benefit is not specified and allows for a wide range of interpretation [2]. Yet the more inconcrete is the answer to the question – "who and how should determine the interests of the individual, the family and even the state?" The national doctrine of education in the Russian Federation, which determined the goals of teaching and upbringing, the ways to attain them by means of the state policy regulating the field of education, the target achievements of the development of the educational system for the period up to 2025, approved by the Decree of the Government of the Russian Federation of October 4, 2000 #751, was abrogated by the Decree of the Government of the Russian Federation of March 29, 2014 #245 [7]. The new doctrine has not been developed so far. The RAE Academician A.B. Khutorsky believes that the absence of the national doctrine of education presents a threat to national security and a violation of the right of citizens to quality education. Accordingly, the teacher has to solve the problem of achieving the harmony of interests of the individual, the family, the society and the government on their own, which, however, judging by the officially published results, is the task that exceeds the abilities of the participants of the educational process.  The particular concern about the results of the patriotic upbringing served as a basis for the legislative initiative of the RF President V. V. Putin, who introduced the project of an amendment to the Law of RF "About Education of the Russian Federation" to the State Duma in 2020, regarding the quality of patriotic upbringing [3]. Patriotism, considered by the President of RF V. V. Putin as the only possible idea to unite the nation is "THE FEELING OF LOVE OF THE MOTHERLAND" and the readiness for every sacrifice and heroic deed for the sake of the interests of your Motherland. However, the practicing educators experience shortfalls in efficient methodologies of patriotic upbringing, which should let them bring up citizens, loving their Motherland more than themselves. The article is dedicated to solution to this problem based on the Value-sense paradigm of upbringing educational dynasty of the Kurbatovs [15].

The Right to Bodily Integrity

2018 ◽  
Author(s):  
Alison Brysk
Keyword(s):  
Sexual Assault ◽  
Sexual Violence ◽  
Public Space ◽  
Transitional Justice ◽  
The United States ◽  
Bodily Integrity ◽  
Global Pattern ◽  
Popular Resistance ◽  
Wide Range ◽  
The Right

In Chapter 7, we profile the global pattern of sexual violence. We will consider conflict rape and transitional justice response in Peru and Colombia, along with the plight of women displaced by conflict from Syria and Central America, and limited international policy response. State-sponsored sexual violence and popular resistance to reclaim public space will be chronicled in Egypt as well as Mexico. We will track intensifying public sexual assault amid social crisis in Turkey, South Africa, and India, which has been met by a wide range of public protest, legal reform, and policy change. For a contrasting experience of the privatization of sexual assault in developed democracies, we will trace campus, workplace, and military rape in the United States.

Lying in Early Modern English Culture

2017 ◽  
Author(s):  
Andrew Hadfield
Keyword(s):  
Early Modern ◽  
Cultural History ◽  
Identity Politics ◽  
Social Life ◽  
Thomas More ◽  
Early Modern English ◽  
Wide Range ◽  
Constant Feature ◽  
The Right ◽  
English Culture

Lying in Early Modern English Culture is a major study of ideas of truth and falsehood from the advent of the Reformation to the aftermath of the Gunpowder Plot. The period is characterized by panic and chaos when few had any idea how religious, cultural, and social life would develop after the traumatic division of Christendom. Many saw the need for a secular power to define the truth; others declared that their allegiances belonged elsewhere. Accordingly there was a constant battle between competing authorities for the right to declare what was the truth and so label opponents as liars. Issues of truth and lying were, therefore, a constant feature of everyday life, determining ideas of identity, politics, speech, sex, marriage, and social behaviour, as well as philosophy and religion. This book is a cultural history of truth and lying from the 1530s to the 1610s, showing how lying needs to be understood in practice and theory, concentrating on a series of particular events, which are read in terms of academic debates and more popular notions of lying. The book covers a wide range of material such as the trials of Anne Boleyn and Thomas More, the divorce of Frances Howard, and the murder of Anthony James by Annis and George Dell; works of literature such as Othello, The Faerie Queene, A Mirror for Magistrates, and The Unfortunate Traveller; works of popular culture such as the herring pamphlet of 1597; and major writings by Castiglione, Montaigne, Erasmus, Luther, and Tyndale.

Tickets for the Inclusive Museum

2020 ◽  
pp. 390-406
Author(s):  
Magda Nikolaraizi ◽  
Charikleia Kanari ◽  
Marc Marschark
Keyword(s):  
Hard Of Hearing ◽  
Learning Experiences ◽  
Learning Needs ◽  
Participatory Learning ◽  
Maximum Benefit ◽  
Wide Range ◽  
The Right ◽  
Physical Features ◽  
And Behavior

In recent years, museums of various kinds have broadened their mission and made systematic efforts to develop a dynamic role in learning by offering a wide range of less formal experiences for individuals with diverse characteristics, including individuals who are deaf or hard-of-hearing (DHH). Despite the worthwhile efforts, in the case of DHH individuals, museums frequently neglect to consider their unique communication, cognitive, cultural, and learning characteristics, thus limiting their access and opportunities for fully experiencing what museums have to offer. This chapter examines the potential for creating accessible museum environments and methods that reflect an understanding of the diverse communication, cognitive, cultural, and learning needs of DHH visitors, all of which enhance their access and participation in the museum activities. The role of the physical features of museum spaces for the access and behavior of DHH visitors is emphasized, together with attention to exhibition methods and the communication and cognitive challenges that need to be considered so DHH visitors can get the maximum benefit. The chapter emphasizes the right of individuals who are DHH to nonformal learning and analyzes how museums could become more accessible to DHH individuals by designing, from the beginning, participatory learning experiences that address their diverse needs.

Sign in / Sign up

Export Citation Format

Share Document