Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Polyamine spermidine.
Дисертації з теми "Polyamine spermidine"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-32 дисертацій для дослідження на тему "Polyamine spermidine".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Catros, Véronique. "Implication des polyamines dans les processus proliferatifs malins." Rennes 1, 1990. http://www.theses.fr/1990REN1T085.
Повний текст джерелаАнотація:
Des etudes effectuees in vivo chez l'animal ainsi que chez des patients atteints de differents types histologiques de tumeurs, ont permis de montrer que le taux erythrocytaire de spermidine (spd) se comportait comme un index sanguin de la proliferation cellulaire tumorale. L'etude in vivo du metabolisme des polyamines (pa) apres administration de precurseurs radiomarques a des animaux porteurs de tumeurs greffees a permis d'apporter la preuve de l'origine tumorale de la spermidine erythrocytaire. Les modalites d'uptake des pa par les erythrocytes ont par ailleurs ete caracterisees in vitro: les erythrocytes de souris cancereuses presentent des modifications de leurs proteines stromales, leur conferant la capacite de capter trois fois plus de #1#4c spd que les erythrocytes de souris saines. A l'inverse de ce qui se passe au cours d'un processus proliferatif controle, ou l'evolution des taux erythrocytaires de pa est parfaitement regulee, en cas de cancer, les pa s'accumulent dans les hematies. Cette accumulation est correlee a une reduction de la concentration tissulaire en malonaldehyde (mda), une molecule inhibitrice de la replication de l'adn. L'etude du catabolisme des pa dans les cellules cancereuses ainsi que l'utilisation de drogues modulatrices de ce metabolisme permettent d'evoquer l'hypothese d'un role des pa erythrocytaires dans le controle homeostatique de la proliferation cellulaire. Les effets biologiques obtenus avec des analogues tetramethyles de pa permettent egalement d'envisager l'utilisation du metabolisme des pa a des fins therapeutiques et diagnostiques en cancerologie
2
Chen, Alina. "New polyamine analogues as potential antineoplastic agents." Scholarly Commons, 2000. https://scholarlycommons.pacific.edu/uop_etds/2680.
Повний текст джерелаАнотація:
The naturally occurring polyamines play an essential role in cell growth and proliferation. The levels of polyamines have been shown to increase in rapidly proliferating cancer cells. Therefore, compounds that inhibit enzymes in polyamine biosynthetic pathway may have therapeutic potential. Compounds capable of providing both in vitro and in vivo inhibition of almost all enzymes in the polyamine biosynthetic pathway are known. An exception is the lack of an agent that inhibits spermidine/spermine N 1 -acetyltransferase (SSAT), the rate-limiting enzyme in the catabolism of polyamines. The design, synthesis and characterization of five new polyamine analogues as potential inhibitors of SSAT are presented. Three compounds, N 1 -[3-(propenamido) propyl]-1,4-diaminobutane dihydrochloride 5 , N 1 -[3-(maleimido)propyl]-1,4-diamino-butane dihydrochloride 7 and N 1 -[3-(2-bromoacetamido)propyl]-1,4-diaminobutane dihydrochloride 9 , were designed as active-site-directed affinity label inhibitors. Two compounds, N-[N-(5-acetamido-2-hydroxypentyl-3-aminopropyl)]-1,4-diaminobutane trihydrochloride 12 and N-[3-(2-hydroxyethylamino)propyl]-1,4-diaminobutane trihydrochloride 14 , were designed as transition state-like analogue inhibitors. These compounds were synthesized using one key intermediate, N-(3-aminopropyl)-N,N ′ -bis-(tert-butoxycarbonyl)-1,4-diaminobutane 3 . Three of these synthesized compounds, 5 , 7 and 12 were evaluated for their ability to inhibit SSAT. The enzyme used was a crude extract of human large cell undifferentiated lung carcinoma cell line NCI H157 cells. These synthetic analogues when tested against the crude enzyme extract at concentrations of 0.05, 0.1, 1 and 5 μM appeared to show no effects on the activity of SSAT.
3
Vaishali, Mulangi Gopala Reddy. "Characterization of Polyamine Transporters from Rice and Arabidopsis." Bowling Green State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1303231265.
Повний текст джерела
4
Li, Jun. "A study of the role of spermidine/spermine N¹-acetyltransferase (SSAT) in polyamine homeostasis in human prostate cancer cells." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210088.
Повний текст джерелаАнотація:
Prostate cancer is the second leading cancer in men. A large amount of polyamines are synthesised in the human prostate and are involved in prostate cell growth and its physiological functions. The content of intracellular polyamines is closely related to cell growth. An increase in cell growth is accompanied by a rise of intracellular polyamine content, and a depletion of intracellular polyamine pools can cause growth arrest or cell death. Therefore, maintaining polyamine concentrations is critical to the cell. Spermidine/spermine N1-acetyltransferase (SSAT) is the first and rate-limiting enzyme in the polyamine catabolic pathway. SSAT gene is highly inducible, with many stimuli including polyamine analogues and some anticancer drugs producing dramatic increases in activity. Many studies have focussed on polyamine analogues as inducers of SSAT activity as increases in SSAT are associated with a growth inhibition in many tumour cells. However, the mechanisms of this inhibition are not fully understood with respect to polyamine content. Additionally, in vivo results in SSAT transgenic mice studies are contradictory. For example, prostate carcinogenesis is reduced in TRAMP mice but Apcmin/+ mice show a promoted intestinal tumorigenesis. It is thus necessary to characterise the regulation of polyamine content and metabolism by SSAT in prostate cancer cells. The aim of the present study was to characterise the role of SSAT in both the growth of LNCaP prostate carcinoma cells and the response of these cells to anticancer drugs. Our hypothesis is that increased SSAT activity will inhibit cell growth and that this is associated with a decrease of intracellular polyamine pools. Furthermore, if SSAT induction is an essential part of the response of cancer cells to anticancer drugs, then altered SSAT activity should affect sensitivity of the cells to the drugs. The present study used a cell culture model of human prostate cancer: LNCaP wild type (WT) and SSAT cDNA transfected prostate carcinoma cell lines. The expression of SSAT in the transfected cell line (SSAT- & SSAT+) was controlled through the “Tet-off” system. This model system provided a background for comparison of effects under basal (WT), low (SSAT-), and high (SSAT+) SSAT activity. Due to our interest in acetylpolyamine derivatives and their low concentrations in cells, a new method for quantifying polyamine concentrations was developed using liquid chromatography-mass spectrometry (LC-MS). This method was highly sensitive and can detect polyamines about 250 fold lower than HPLC, as well as N-acetylpolyamines and N1,N12-diacetylspermine. In addition, a variety of methods were utilised to measure cell growth, enzyme activity, protein expression, polyamine efflux and apoptosis, which includes enzyme assays, western blot, radiochemical labelled assays, flow cytometry, spectrophotometry and fluorescent microscopy. A stable increase in SSAT activity was inhibitory to the cell growth. This inhibition was associated with significant changes in the activity of the polyamine pathway. The alterations included an increase in ODC, APAO, and SMO activity; an accumulation of intracellular N1-acetylspermidine and putrescine; a decrease in intracellular spermidine and spermine; an increased polyamine flux and efflux; and an increase in apoptosis. Combination treatment to the cells with DFMO and MDL72527 partially restored the growth of SSAT+ cells. The original contribution of this study to the field is that the cells with a higher SSAT activity are less sensitive to aspirin and 5-FU, and the sensitivity increased while the overexpressed SSAT activity decreased. The growth inhibition was associated with a depletion of total intracellular polyamine pools by the drug treatments. Moreover, to our knowledge, it is first time that the extracellular polyamine concentrations were quantified by LC-MS in human tumour cells. Overall, an increase in SSAT activity led to an inhibition of prostate cancer cell growth, and vice versa. Thereby, this study suggests that SSAT is a potential target for novel drug discovery for cancer chemotherapy or chemoprevention. For example, a combination treatment could be designed that acts as an inducer of SSAT activity in tumour cells, leading to an inhibition of the cell growth in the first place and increased sensitivity to cytotoxic agents. This would then be followed by an agent to decrease SSAT activity when the sensitivity of cancer cells to the cytotoxic treatment was optimal.
5
Ariyaratne, Menaka M. "A new perspective on polyamine biosynthesis and transport in arabidopsis thaliana." Bowling Green State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1555693507751475.
Повний текст джерела
6
Fredericks, Eugene B. (Eugene Bernard). ""Studies involving alterations of polyamine metabolism in Arabidopsis thaliana"." Monash University, Dept. of Biological Sciences, 2001. http://arrow.monash.edu.au/hdl/1959.1/8432.
Повний текст джерела
7
AUBEL, CORINNE. "Effet d'une carence en acide amine sur deux mecanismes majeurs de l'homeostasie des polyamines : le transport membranaire et le catabolisme par la spermidine/spermine n1-acetyltransferase (doctorat)." Clermont-Ferrand 1, 2001. http://www.theses.fr/2001CLF1MM13.
Повний текст джерела
8
Rioux, Benjamin. "Synthèse et vectorisation de biomolécules type Chalcone en vue d'une application anticancéreuse." Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0104/document.
Повний текст джерелаАнотація:
La synthèse et la vectorisation d’agents anticancéreux constituent des axes de recherche majeurs du LCSN. De nombreux composés naturels possèdent des propriétés anticancéreuses, mais ils sont abandonnés en raison de leur manque de sélectivité vis-à-vis des cellules cancéreuses ou de leur faible biodisponibilité. Ainsi, un grand intérêt est actuellement porté sur le développement de médicaments spécifiquement vectorisés vers les cellules cancéreuses. Les vecteurs utilisés dans ce travail sont des dérivés de polyamines et des nano objets de type β-cyclodextrines / nanocristaux de cellulose (β-CD/CNCx). Les polyamines vont permettre un ciblage actif des cellules cancéreuses grâce au système de transport de polyamine (PTS) surexprimé dans ces cellules. Les nano objets vont cibler spécifiquement les tumeurs via un ciblage passif dû à l’effet EPR. Les principes actifs employés dans cette étude sont des flavonoïdes, et plus particulièrement des chalcones. En effet, les flavonoïdes, qui constituent une large famille de composés phénoliques naturels, sont connus pour leurs nombreux effets biologiques comme les activités antioxydantes, anti-inflammatoires et anti-prolifératives.L’intérêt du LCSN à la fois pour les chalcones et les agents anticancéreux nous a conduits à concevoir de nouveaux composés antiprolifératifs vectorisés. Ce travail présente dans un premier temps la synthèse de chalcones et l’obtention de dérivés couplés aux différents vecteurs décrits précédemment (motifs polyaminés,β-CD/CNCx) ; un travail sur la synthèse d’une bis-chalcone via le couplage de Suzuki est également exposé.L’ensemble des molécules obtenues est caractérisé par des analyses RMN 1H, 13C et HRMS. Dans une seconde partie, nous présentons l’ensemble des évaluations biologiques des composés précédemment obtenus. Ces évaluations sont réalisées par un test de viabilité cellulaire (test MTT) sur quatre lignées cancéreuses : deux colorectales (HT-29 et HCT-116) et deux prostatiques (PC-3 et DU-145)Synthesis and vectorization of anticancer agents are major research themes of LCSN. Many natural compoundspossess anti-cancer properties, but they are dropped because of their lack of selectivity to cancer cells or theirlow bioavailability. Thus, great interest is currently focused on the development of drugs specifically vectorizedto cancer cells. The vectors used in this work are polyamine derivatives and nano-objects type β-cyclodextrin /cellulose nanocrystals (β-CD/CNCx). Polyamines allow active targeting of cancer cells through the polyaminetransport system (PTS) overexpressed in these cells. Nano-objects specifically target tumors using a passivetargeting due to the EPR effect. Drugs used in this study are flavonoids, especially chalcones. Indeed,flavonoids, which constitute a large family of natural phenolic compounds, are known for their numerousbiological effects such as antioxidant, anti-inflammatory and anti-proliferative activities. The interest of LCSNfor both chalcones and anticancer agents led us to design new vectorized anti-proliferative compounds. Firstly,this work shows the synthesis of chalcones and their derivatives coupled to various above-described vectors(polyamines units, β-CD/CNCx); a work on the synthesis of a bis-chalcone through the Suzuki coupling reactionis also exposed. All molecules obtained are characterized by 1H NMR, 13C NMR and HRMS analysis. In thesecond part of this work, we present all biological evaluations of compounds previously obtained. Theseassessments are performed through a cell viability test (MTT test) on four cancer cell lines: two colorectal (HT-29 and HCT-116) and two prostate (PC-3 and DU-145) cell lines
9
Chiteri, Kevin Oyale. "Functional & Phylogenetic Analysis of Arabidopsis thaliana Organic Cation Transporters (OCT5 & OCT1) Genes in Polyamine Transport in Plants." Bowling Green State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1563038129138996.
Повний текст джерела
10
Ménard, Florian. "Benzoporphyrines polyaminées et glycolisées : synthèses et tests biologiques." Limoges, 2008. https://aurore.unilim.fr/theses/nxfile/default/8fa60a2e-636b-4c5d-b022-4d474de42c60/blobholder:0/2008LIMO4065.pdf.
Повний текст джерелаАнотація:
Ce travail porte sur la synthèse multi-étapes, la caractérisation et l'évaluation biologique de nouveaux photosensibilisateurs vectorisés conçus pour une utilisation potentielle en photothérapie dynamique des cancers. Nous avons élaboré plusieurs tétrabenzoporphyrines symétriques substituées par quatre polyamines ou quatre molécules de glucose, dans le but d’augmenter leur sélectivité pour les cellules cancéreuses. Ces dérivés de benzoporphyrines ont été obtenus suivant deux approches distinctes. Ainsi, la fixation des vecteurs (spermidine, spermine, α-D-glucose ou β-D-glucose) a été effectuée soit en fin de synthèse, directement sur le précurseur macrocyclique, soit dans la phase initiale, sur le synthon aldéhydique. Tous les produits finaux obtenus ont révélé leur aptitude à produire de l’oxygène singulet en présence de lumière visible ; finalement, des tests de viabilité cellulaire ont été réalisés, in vitro, sur deux lignées cancéreuses humaines (MCF-7 et HaCaT)This work reports the multi-step synthesis, characterization and biological evaluation of new vectorized photosensitizers designed for their potential use in phototherapy of cancers. This series of molecules consisted in symmetrical tetrabenzoporphyrins to which four glucosyl or polyamine units have been attached in order to increase their selectivity for cancer cells. These benzoporphyrin derivatives were obtained through two distinct approaches: attachment of the vectors (spermidine, spermine, α-D-glucose or β-D-glucose) has been carried out either at the very end of synthesis, on the macrocyclic precursor, or during the initial step, on the aldehydic synthon. All of these final products have proved their ability to produce singlet oxygen in the presence of visible light, and their effects on cell viability have been tested, in vitro, on two human cancer cell lines (MCF-7 and HaCaT)
11
Gomes, Guilherme Monteiro. "Agentes poliaminérgicos modulam a extinção do medo condicionado contextual em ratos." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/11118.
Повний текст джерелаАнотація:
Conselho Nacional de Desenvolvimento Científico e TecnológicoPolyamines, such as spermidine and spermine, have been reported to improve memory retention through the activation of N-methyl-D-aspartate receptors (NMDAr). However whether polyamine agonists and antagonists alter extinction remains unclear. In the current study, we investigated whether spermidine and polyamine antagonists that selectively block the NR2B subunit at the NMDAr alter the extinction of contextual conditioned fear in male Wistar rats. While the bilateral intrahippocampal administration of exogenous spermidine (2 nmol/site) facilitated the extinction of fear conditioning, the injection of the antagonists arcaine (0.2 nmol/site), ifenprodil (20 nmol/site) and traxoprodil (0.2 nmol/site), disrupted fear extinction. NMDAr antagonists, at doses that had no effect per se, reversed the facilitatory effect of spermidine on fear extinction. These results suggest that exogenous and endogenous polyamines facilitate the extinction of contextual conditioned fear through activation of NR2B subunit-containing NMDAr in the hippocampus. Since extinction-based exposure therapy is widely used as treatment for a number of anxiety-related disorders, including phobias and post-traumatic stress, the currently reported facilitation of extinction by polyaminergic agents suggest these compounds as putative candidates for drug development.
As poliaminas, como espermidina e espermina, são aminas alifáticas que estão presentes no sistema nervoso central e que se ligam na subunidade NR2B do receptor N-metil-D-aspartato (rNMDA). Tem-se demonstrado que a administração sistêmica, intrahipocampal e intraamígdala de poliaminas melhoram a aquisição e retenção da memória em ratos. Entretanto, seu efeito sobre a extinção do medo condicionado não foi investigado. No presente estudo, investigamos se a administração intrahipocampal de espermidina e de antagonistas seletivos para a subunidade NR2B do rNMDA alteram a extinção do medo condicionado contextual em ratos Wistar machos. A administração intrahipocampal de espermidina (2 nmol/sítio) facilitou a extinção do medo condicionado, enquanto que a injeção dos antagonistas do rNMDA, arcaína (0,2 nmol/sítio), ifenprodil (20 nmol/sítio) e traxoprodil (0,2 nmol/sítio), bloquearam a extinção do medo condicionado contextual. Já a administração dos antagonistas do rNMDA, em doses sem efeito per se, reverteu a facilitação da extinção induzida por espermidina. Estes resultados sugerem que as poliaminas facilitam a extinção do medo condicionado contextual através da ativação da subunidade NR2B do rNMDA hipocampal. Tendo em vista que a terapia baseada em exposição é um método amplamente utilizado como tratamento para diversos tipos de distúrbios relacionados com ansiedade, incluindo fobias e estresse pós-traumático, a facilitação da extinção causada pela administração de espermidina coloca este composto com um possível candidato para o desenvolvimento de novos fármacos para o tratamento destas patologias.
12
Almeida, Maria de Lurdes Soares de. "Selective protection of polyamines : Synthesis of spermidine derivatives." Doctoral thesis, Universidade do Porto. Reitoria, 1989. http://hdl.handle.net/10216/10192.
Повний текст джерела
13
Almeida, Maria de Lurdes Soares de. "Selective protection of polyamines : Synthesis of spermidine derivatives." Tese, Universidade do Porto. Reitoria, 1989. http://hdl.handle.net/10216/10192.
Повний текст джерела
14
Caron, Édith. "Étude de l'interaction entre l'actine et les polyamines : spermidine et spermine." Thèse, Université du Québec à Trois-Rivières, 1987. http://depot-e.uqtr.ca/5803/1/000560724.pdf.
Повний текст джерела
15
Gingras, Yves. "L'effet inhibiteur des polyamines spermine et spermidine sur le complexe protéique du photosystème II /." Thèse, Trois-Rivières, Université du Québec à Trois-Rivières, 1998. http://www.uqtr.ca/biblio/notice/tablemat/03-2195690TM.html.
Повний текст джерелаАнотація:
Mémoire (M.Sc.) - Université du Québec à Trois-Rivières, 1998.La table des matières est disponible en format électronique sur le site Web de la bibliothèque. CaQTU Bibliographie : f. [147]-158.
16
Gingras, Yves. "L'effet inhibiteur des polyamines spermine et spermidine sur le complexe protéique du photosystème II." Thèse, Université du Québec à Trois-Rivières, 1998. http://depot-e.uqtr.ca/3546/1/000654648.pdf.
Повний текст джерела
17
Chakrabarti, Nilanjana. "Functional Analysis and Characterization of Transporter of Putrescine and Spermidine (TOPAS1) in Phytophthora parasitica." Bowling Green State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu149874256456224.
Повний текст джерела
18
Vargas, Ashley Joy. "Assessing the Role of Dietary Polyamines on the Continuum of Colorectal Carcinoma." Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/293416.
Повний текст джерелаАнотація:
Putrescine, spermidine and spermine are the polyamines biosynthesized by human cells via ornithine decarboxylase (ODC) and are also sourced from the diet. Polyamines are required for malignant and normal cell growth and development. Pharmacological suppression of polyamine biosynthesis, by difluoromethylornithine, and inflammation, via sulindac, has demonstrated ~70% efficacy in preventing premalignant colorectal adenomas (CRA) in a clinical trial; however, high polyamine intakes mitigated this preventative action. Further, dietary polyamines increase the dysplasia of CRA in initiated animal models of colorectal cancer (CRC) and are hypothesized to function as tumor promoters. Human research on dietary polyamines was limited until the development of a dietary database in 2007 but, continues to be limited by the lack of a biomarker of exposure. Chapter 1 of this dissertation tests the hypothesis that dietary polyamines increase risk of CRA in polyp-formers (n = 1164) and found evidence to support this hypothesis. However, only women, younger participants and certain genotypes experienced more risk of CRA with high polyamine exposure. Chapter II tests the hypothesis that dietary polyamines increase the risk for CRC in an average risk cohort of post-menopausal women (n = 87,620) and did not find evidence to support this hypothesis in the whole population. Rather, dietary polyamines were non-significantly protective against CRC and significantly protective when paired with aspirin use and against CRC-specific death. There was some evidence to support an increase in risk of CRC in younger participants with high polyamine exposure. Overall, the first two chapters suggest that dietary polyamines protect the colorectum in normal risk individuals but promote carcinogenesis in high risk individuals. Chapter III tests the hypothesis that dietary polyamine intake correlates with urinary polyamine output in a group of overweight/obese, older men (n = 36) and Chapter IV tests the hypothesis that intake of highly ripe sweet cherries will increase urinary polyamine output in a subgroup of 10 men from Chapter III. The findings from these chapters suggest there may be a positive correlation, but that a better measure of dietary polyamine intake is needed to determine if urinary polyamines are biomarkers of exposure to polyamines.
19
Bergeron, Christophe. "Les polyamines : agents diagnostiques et cibles thérapeutiques en oncologie pédiatrique." Rennes 1, 1993. http://www.theses.fr/1993REN1B006.
Повний текст джерела
20
Léon, Patrick. "Alkylation d'amines par les sels de sulfonium, reaction de type gabriel et synthese de polyamines." Paris 6, 1987. http://www.theses.fr/1987PA066488.
Повний текст джерела
21
Bauer, Julia [Verfasser], and Florian [Akademischer Betreuer] Lang. "Der suizidale Zelltod humaner Erythrozyten - Stimulation durch Sphingosin und Auswirkungen der biogenen Polyamine Spermin und Spermidin / Julia Bauer ; Betreuer: Florian Lang." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1160754489/34.
Повний текст джерела
22
Martignoni, Felipe Villa. "TRAXOPRODIL ATENUA AS CONVULSÕES INDUZIDAS POR PENTILENOTETRAZOL." Universidade Federal de Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/8951.
Повний текст джерелаАнотація:
There is evidence that while polyamines facilitate seizures by positively modulating N-methyl-D-aspartate receptors (NMDAr), selective antagonists of the NR2B-subunit decrease seizures. However, it remains undetermined whether traxoprodil (CP-101,606), an ifenprodil analog that acts as a selective antagonist of the NR2B subunit of the NMDAr, decreases seizure activity. In the current study we investigated whether traxoprodil alters PTZ-induced seizures in adult male Wistar rats by behavioral and electroencephalographical methods. Spermidine (SPD) (2 nmol/site; i.c.v.) facilitated behavioral and electroencephalographical seizures induced by a normally subeffective dose of PTZ (35 mg/kg; i.p.), but did not alter seizure activity induced by convulsant dose of PTZ (70 mg/kg; i.p). Traxoprodil (20 nmol i.c.v.) increased the latency to generalized tonic clonic seizures induced by PTZ (70 mg/kg; i.p). The oral administration of traxoprodil (60 mg/kg) increased the latency to clonic and tonic-clonic seizures, and decreased total time spent in seizures. These data constitute pharmacological evidence supporting a role for NR2B subunit in PTZ-induced seizures. While more studies are necessary to determine whether traxoprodil is a useful anticonvulsant in clinical settings, NR2B subunits may represent new targets of drug development for convulsive disorders.Há evidências de que as poliaminas facilitam convulsões por modular positivamente os receptores N-metil-D-aspartato (NMDAr), e que os antagonistas seletivos a subunidade NR2B do NMDAr têm atividade anticonvulsivante. Entretanto, permanece indeterminado se o traxoprodil (CP-101,606), um análogo do ifenprodil que age como antagonista seletivo na subunidade NR2B do NMDAr, tem efeito anticonvulsivante. Neste estudo investigamos se o traxoprodil altera as convulsões induzidas por pentilenotetrazol (PTZ) em ratos Wistar machos por meio de métodos comportamentais e eletroencéfalográficos (EEG). Espermidina (SPD) (2 nmol/sítio; i.c.v.) facilita as convulsões comportamentais e eletroencéfalográficas induzidas por doses subconvulsivantes de PTZ (35 mg/kg; i.p.), mas não altera a atividade convulsiva induzida por dose plenamente convulsivante de PTZ (70 mg/kg; i.p.). Traxoprodil (20 nmol i.c.v.) aumenta a latência para convulsão tônico-clônica generalizada induzida por PTZ (70 mg/kg; i.p.). A administração oral de traxoprodil (60 mg/kg) aumenta as latências para convulsão clônica e tônico-clônica generalizada e diminui a duração total das convulsões induzidas por PTZ (70 mg/kg; i.p.). Esses dados mostram que o traxoprodil diminui as convulsões induzidas por PTZ, um modelo animal com bom poder de predição de atividade convulsivante em humanos, e sugerem um papel para a subunidade NR2B nas convulsões induzidas por PTZ. Enquanto mais estudos são necessários para determinar se o traxoprodil tem, de fato, atividade anticonvulsivante na clínica, as subunidades NR2B podem representar um novo alvo para o desenvolvimento de drogas anticonvulsivantes.
23
Ceretta, Ana Paula Chiapinotto. "Administração sistêmica de espermidina e arcaína altera a memória da tarefa de esquiva inibitória em ratos: envolvimento da dependência de estado." Universidade Federal de Santa Maria, 2006. http://repositorio.ufsm.br/handle/1/11145.
Повний текст джерелаАнотація:
The polyamines, putrescine, spermidine and spermine, are present in high concentrations in the central nervous system and, because of their policationic nature, they can interact with diverse cellular anionic targets (nucleic acids and proteins) and modulate the learning and memory by interacting with the polyamine binding site at N-methyl-D-aspartate receptor. In this study we investigated the effects of the systemic administration of spermidine and arcaine on the memory of the inhibitory avoidance task in rats. It was also determined whether the effects of the spermidine and arcaine involve state dependence. The animals were trained in an inhibitory avoidance apparatus (0.4 mA, 3s) and tested in the same apparatus 24 hours later. Immediate post-training administration of spermidine (50 mg/kg, i.p.) improved, while arcaine (10 and 30 mg/kg, i.p.) impaired step-down latencies in the inhibitory avoidance test. Administration of spermidine (50 mg/kg, i.p.) 15 minutes before testing did not alter the performance of rats which were injected with spermidine (50 mg/kg, i.p.) or vehicle immediately after training. However, administration of arcaine (30 mg/kg, i.p.) 15 minutes before testing reverted the impairment of memory caused by the administration of arcaine (30 mg/kg, i.p.) immediately after training. Administration of arcaine (30 mg/kg, i.p.) or MK-801 (0.03 mg/kg, i.p.) before testing partially reverted the impairment of memory caused by the administration of arcaine (30 mg/kg, i.p.) or MK-801 (0.03 mg/kg, i.p.) immediately after training, characterizing a crossed state dependence. The results suggest that memory improvement caused by the administration of spermidine immediately after training is not due to state dependence. In contrast, the impairment of memory induced by arcaine is due to state dependence. The crossed state dependence between arcaine and MK-801 supports that state dependence induced by arcaine is related to NMDA receptor hypofunction.As poliaminas, putrescina, espermidina e espermina estão presentes em altas concentrações no sistema nervoso central e, por sua natureza policatiônica, podem interagir com sítios aniônicos de macromoléculas (ácidos nucléicos e proteínas) e modulam o aprendizado e a memória interagindo com o sítio de ligação das poliaminas no receptor N-metil-D-apartato. Neste estudo nós investigamos os efeitos da administração sistêmica de espermidina e arcaína sobre a memória da tarefa de esquiva inibitória em ratos. Também foi determinado se os efeitos da espermidina e arcaína envolvem dependência de estado. Os animais foram treinados em um aparelho de esquiva inibitória (0,4 mA, 3 seg) e testados no mesmo aparelho, 24 horas depois. A administração imediatamente após o treino de espermidina (50 mg/kg, i.p.) melhorou, enquanto que arcaína (10 e 30 mg/kg, i.p.) prejudicou a latência de descida da plataforma no teste da esquiva inibitória. A administração de espermidina (50 mg/kg, i.p.) 15 minutos antes do teste não afetou a performance dos ratos que foram injetados com espermidina (50 mg/kg, i.p.) ou veículo imediatamente após o treino. Entretanto, a administração de arcaína (30 mg/kg, i.p.) 15 minutos antes do teste reverteu o prejuízo da memória causado pela administração de arcaína (30 mg/kg, i.p.) imediatamente após o treino. A administração de arcaína (30 mg/kg, i.p.) ou MK-801 (0,03 mg/kg, i.p.) antes do teste reverteu parcialmente o prejuízo da memória causado pela administração de arcaína (30 mg/kg) ou MK-801 (0,03 mg/kg) imediatamente após o treino, caracterizando dependência de estado cruzada. Estes resultados sugerem que a melhora da memória causada pela administração de espermidina imediatamente após o treino não é devido à dependência de estado. Em contraste, o prejuízo da memória induzido pela arcaína é devido a uma dependência de estado. A dependência de estado cruzada entre arcaína e MK-801. sugere que a dependência de estado induzida pela arcaína envolve a hipofunção do receptor NMDA.
24
Plym, Forshell Tacha Zi. "Examining the role of metabolism in Myc-driven tumorigenesis." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-46564.
Повний текст джерелаАнотація:
Myc transcriptionally regulates genes involved in processes such as cell proliferation, metabolism, differentiation, and angiogenesis. MYC expression is deregulated in many types of human cancer; therefore discovering the mechanisms behind MYCs role in tumorigenesis is essential. In this dissertation, I have focused on several Myc target genes, Spermidine synthase (Srm); Lactate dehydrogenase (Ldh); 3-phosphoglycerate dehydrogenase (Phgdh); Serine hydroxymethyltransferase (SHMT) 1 and 2; and Pim-3 (a member of the Pim family of serine/threonine kinases). These enzymes play a role in various functions: Spermidine synthase (polyamine synthesis); Lactate dehydrogenase (glycolysis); Phgdh and Shmt (serine metabolism); and Pim-3 (cell signaling). In order to elucidate the impact Myc over-expression has on metabolism in tumorigenesis, we use human cell lines, and transgenic mice as well as cell lines and tissues derived from these mice. The impact of inhibition of these target genes on Myc-driven tumorigenesis was done by genetically inhibiting the target gene (using RNAi or mouse models) or inhibiting the protein with a chemical inhibitor. Investigating these Myc target genes will help determine if inhibition of Myc target genes is a viable approach for chemotherapeutics, and under what conditions this inhibition may be the most valuable. In paper I, we examine SRM; a highly expressed enzyme in the polyamine synthesis pathway that converts putrescine to spermidine, and is important for actively growing cells. Genetic inhibition via RNAi against Srm, or chemical inhibition of Srm, resulted in decreased proliferation of B-cell tumor lines from transgenic mice in vitro. In vivo treatment of λ-Myc transgenic mice with a chemical SRM inhibitor exhibited a significant chemopreventative effect on tumor formation. These results support previous findings that inhibition of polyamine synthesis pathway enzymes has a place in cancer therapy. Many Myc target genes have been suggested as attractive targets in battling Myc-driven tumorigenesis. Surprisingly in paper II, when we analyzed the inhibition of other Myc target genes, such as Ldh, Shmt, and Phgdh, we found that inhibition of these genes did not inhibit Myc-driven tumorigenesis to any significant degree. However, inhibition of Ldh, Phgdh and Shmt2 had a notable effect on in vitro Ras-driven transformation. These findings suggest that chemotherapeutic inhibition of metabolic genes such as Ldh, Phgdh and Shmt2 may be effective in genetically defined settings, keeping in mind the oncogenic lesion behind the tumor. The Pim kinase family consists of three serine/threonine kinases, Pim1-3. In paper III, we found that Pim-3 is a direct Myc target gene and that Pim-3 expression is high in Burkitt Lymphoma samples taken from human patients, as well as spontaneously arising lymphomas from Myc transgenic mice. We also found that inhibition of Pim-3 using a pan-Pim kinase inhibitor, Pimi, in these spontaneously arising Myc lymphomas resulted in caspase independent cell death. These results indicate that Pim kinase inhibition may be a potential chemotherapeutic strategy in human lymphomas that rely on Pim-3 kinase expression.
25
Прилуцький, Максим Петрович. "Розробка біосенсорних платформ та базових алгоритмів аналізу для експресної діагностики раку грудної залози людини в умовах in vitro". Doctoral thesis, Київ, 2020. https://ela.kpi.ua/handle/123456789/37315.
Повний текст джерелаАнотація:
Робота виконана на кафедрі лабораторної діагностики біологічних систем, факультету захисту рослин Національного університету «Києво-Могилянська академія».В дисертації описано розробку методики визначення поліамінів в культурі клітин лінії MCF-7 та в сироватці крові хворих на рак грудної залози і вивчення біологічних властивостей поліамінів, як потенційних маркерів раку грудної залози. Окрім того, порівняно декілька типів біосенсорних пристроїв, в яких використаний різний підхід до сенсибілізації чутливої поверхні трансдюсера, а також порівняно декілька типів трансдюсерної поверхні для визначенння найчутливішої біосенсорної платформи. Для створення ефективної біосенсорної платформи було порівняно декілька алгоритмів аналізу з використанням біосенсора, аби визначити найчутливіший та найефективніший. Серед усіх використаних алгоритмів аналізу найвищу ефективність показав прямий алгоритм аналізу, за якого специфічні антитіла та поліаміни були іммобілізовані безпосередньо на поверхні трансдюсера без додаткової модифікації. Наступним етапом стало визначення межей чутливості біосенсора з прямим алгоритмом аналізу. Діапазон чутливості новоствореного біосенсора знаходиться в межах 5-1000 нг/мл. Ефективність аналізу покращилася після модифікації поверхні трансдюсера додатковими речовинами, що дозволило збільшити чутливість поверхні трансдюсера, зорієнтувати антитіла специфічними до поліамінів ділянками та заблокувати неспецифічні місця зв’язування. Надалі було порівняно ефективність новоствореної методики біосенсорного аналізу з біосенсором на основі фотолюмінесценції оксиду цинку. Біосенсор на основі явища поверхневого плазмонного резонансу виявився кращим у індикації поламінів у модельних розчинах та культурі клітин лінії раку грудної залози людини MCF-7 на 14-30% порівняно з біосенсором на основі фотолюмінесценції оксиду цинку. Окрім того, трасдюсер на основі золота здатен у 1,5-2 рази краще визначати поліаміни в культурі клітин і модельних розчинах. На останньому етапі досліджень було встановлено, що зсув резонансного кута в контрольних сироватках крові не перевищував меж у 5 -10 нг/мл, а у зразках крові хворих на рак грудної залози концентраціях поліамінів перебувала в діапазоні від 20 до 100 нг/мл, що перевищує фізіологічні рівні. За отриманими результатами розроблений біосенсорний метод дозволяє виявити як низькі, так і високі концентрації поліамінів. Новостворена біосенсорна платформа може виявляти поліаміни в розчині та в культурі клітин in vitro в наномолярних концентраціях, а також в сироватці крові, що робить її актуальною та перспективною для подальшого вдосконалення і використання.
26
Signor, Cristiane. "EFEITO DA ESPERMIDINA SOBRE A PERSISTÊNCIA DA MEMÓRIA EM RATOS." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/11211.
Повний текст джерелаАнотація:
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe long-term memory involves three stages: acquisition, consolidation and extinction. However was recently described a new phase of consolidation, called the persistence of memory. At this stage, crucial events occur 12 hours after the acquisition, in which the synthesis of new proteins and brain derived neurotrophic factor, are essential. The polyamines putrescine, spermidine and spermine, they act as endogenous modulators of various ion channels, including the glutamatergic receptor subtype N-methyl-D-aspartate. Systemic and intra-cerebral spermidine, immediately after training, improves memory in various tasks in rats. However, no studies demonstrating the effect of spermidine on the persistent memory. Thus, we investigated the effect of systemic administration of spermidine, and arcaine, antagonist of polyamine site on the N-methyl-D-aspartate, the persistence of memory, through the task of contextual fear conditioning. For this study, were used adult male Wistar rats, which underwent a training session on the task of contextual fear conditioning, and 12 hours after training, received a systemic administration of spermidine (0.1-30 mg/kg ), arcaine (0.1-10 mg/ kg) or the combination of spermidine and arcaine. In the second or the seventh day after training the mice were tested. Systemic administration of spermidine improved, whereas systemic administration of impaired arcaine the persistence of memory, when the rats were tested in the second and seventh day after training. The arcaine (0.1 mg / kg) in a dose that has no effect per se prevented improved starry induced by spermidine (10 mg/kg), whereas spermidine (1 mg/kg) dose not effect per se has prevented the worsening of starry arcaine induced (10 mg/kg), when the rats were tested in the second and seventh day after training. These results suggest the involvement of spermidine in persistent memory in rats.
A memória de longa duração envolve três fases: aquisição, consolidação e evocação. No entanto, recentemente foi descrita uma nova fase de consolidação, denominada de persistência da memória. Nesta fase, ocorrem eventos cruciais 12 horas após a aquisição, na qual a síntese de novas proteínas e do fator neurotrófico derivado do encéfalo, são essenciais. As poliaminas putrescina, espermidina e espermina, atuam como moduladores endógenos de diversos canais iônicos, incluindo o subtipo de receptor glutamatérgico N-metil-D-aspartato. A administração sistêmica e intra-cerebral de espermidina, imediatamente após o treino, melhora a memória em diversas tarefas em ratos. Entretanto, não há estudos demonstrando o efeito da espermidina sobre a persistência da memória. Assim, nós investigamos o efeito da administração sistêmica de espermidina, e de arcaína, antagonista do sítio das poliaminas no receptor N-metil-D-aspartato, na persistência da memória, através da tarefa de medo condicionado contextual. Para este estudo, foram utilizados ratos Wistar machos adultos, os quais, foram submetidos a uma sessão de treino na tarefa de medo condicionado contextual, e 12 horas após o treinamento, receberam uma administração sistêmica de espermidina (0,1-30 mg/kg), arcaína (0,1-10 mg/kg) ou a associação de espermidina e arcaína. No segundo ou no sétimo dia após o treino os ratos foram submetidos ao teste. A administração sistêmica de espermidina melhorou, enquanto que a administração sistêmica de arcaína prejudicou a persistência da memória, quando os ratos foram testados no segundo e no sétimo dia após o treino. A arcaína (0,1 mg/kg) na dose que não possui efeito per se, preveniu a melhora da persistência da memória induzida pela espermidina (10 mg/kg), enquanto que a espermidina (1 mg/kg) na dose que não possui efeito per se, preveniu a piora da persistência da memória induzida pela arcaína (10 mg/kg), quando os ratos foram testados no segundo e no sétimo dia após o treino. Estes resultados sugerem o envolvimento da espermidina na persistência da memória em ratos.
27
Giourmas, Nicholas. "The potential therapeutic effect of spermidine supplementation on the mdx mouse phenotype." Thesis, 2021. https://vuir.vu.edu.au/43403/.
Повний текст джерелаАнотація:
Duchenne Muscular Dystrophy (DMD) is one of the most severe forms of inheritable muscular dystrophies that affects 1 in every 5,000 boys. DMD is caused by a genetic mutation on the X chromosome, which results in the loss of the full-length protein, dystrophin. Dystrophin plays a stabilising role by connecting the cytoskeleton of muscle fibres to the extracellular matrix, with the absence of dystrophin directly correlating with the severity of DMD. It has been previously shown that the drug, rapamycin, improves dystrophic muscle function, in part, through the upregulation of the process known as autophagy. This autophagic process plays a role in degrading/removing damaged molecules, including lipids and proteins. Long term use of rapamycin, however, may result in toxic side effects that makes its use as a DMD treatment limited. Because of this, finding a non-toxic inducer of autophagy may be beneficial in treating DMD. One molecule that is known to activate autophagy in a range of tissues, including skeletal muscle, is the polyamine spermidine.
28
Wu, Wei-Zhi, and 吳偉誌. "Investigating the roles of polyamine-spermidine biosynthetic enzyme and nitric oxide in root growth of Nicotiana benthamiana by virus-induced gene silencing." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/r5ae94.
Повний текст джерелаАнотація:
碩士國立彰化師範大學
生物學系
102
Polyamines and the biosynthesis of the corresponding enzymes have been implicated in environmental stresses and plant growth. Another NO (Nitric oxide) is a highly diffusible gaseous free radical involved in plant stress-related substance. However, the roles of polyamine and nitric oxide in root growth have not been fully elucidated. In this study, Nicotiana benthamiana was used as a model plants to investigate the roles of polyamine in root growth. Genes encoding polyamine biosynthesis enzymes were knocking down by using the virus-induced gene silencing (VIGS) strategies. Analysis of root growth was carried out in the spermidine synthase (SPDS)-silenced plants. In NbSPDS-silenced plants, it was observed that the number of lateral roots was decreased as compared to vector-control plants. The effects of VIGS on gene expression level were validated by using reverse transcription-PCR. The expression of genes encoding Tobacco rattle virus (TRV) coat protein was detected in the VIGS-treated root tissues. When compared with the vector-control lines, the expression of NbSPDS gene was significantly decreased. The NO level was higher in the NbSPDS-silenced plants than that of vector-control and wild-type plants. High performance liquid chromatography analysis of polyamine content showed that the content of spermidine was decreased in the NbSPDS-silenced plants as compared to the vector-control plants. Moreover, the VIGS technology was apply for abiotic stress. In summary, this study suggests that spermidine may play important roles in root growth.
29
Popelková, Zuzana. "Obsah polyaminů ve vybraných produktech." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-362508.
Повний текст джерелаАнотація:
The theoretical part of my thesis focuses on venison, its composition and effects and formation of polyamines in the body. The practical part deals with the content of polyamines (putrescine, spermidine, spermine) in roe deer, red deer and wild boar's ridge. Polyamines were determined by high performance liquid chromatogramy. The influence of the preservation method and the kind of venison was researched on the total amount of the polyamines and the contents of individual polyamines. The total amount of polyamines is decreased during storage in roe deer, red deer and wild boar. The highest concentrations were measured spermidine in roe deer and red deer, whether chilled or frozen meat. The boar ridge was found most spermine. Kind of venison did not affect the content of polyamines. Polyamines occurred about the same amount as in roe deer, red deer and boar meat.
30
POJER, Pavel. "Výskyt biologicky účinných aminů a polyaminů ve vybraných druzích zrajících sýrů." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-50690.
Повний текст джерела
31
Montemayor, Eric John 1979. "Biochemical studies of spermidine/spermine N¹-acetyltransferase, an important regulator of cellular polyamines." 2008. http://hdl.handle.net/2152/17941.
Повний текст джерелаАнотація:
The polyamines spermine and spermidine play important roles in many cellular processes, and unusual levels of these polyamines have been associated with numerous human diseases. Spermidine/spermine N¹-acetyltransferase (SSAT) is an enzyme involved in polyamine regulation, where acetylation of polyamines by SSAT ultimately leads to their degradation or export from the cell. In this dissertation, x-ray crystallography and nuclear magnetic resonance (NMR) are used to provide insights into the structure and function of this important enzyme. X-ray crystallography provided two distinct views of SSAT: one of the enzyme in complex with coenzyme A (CoA), and another of the enzyme in complex with CoA and the polyamine spermine. Together, the two structures reveal structural plasticity in the active site of the enzyme. The complex with spermine provides a direct view of polyamine binding by SSAT, and shows that the enzyme relies heavily on associated water molecules to bind spermine; these water molecules also appear to form a "proton relay" between the primary amine of spermine and the side-chain of a conserved glutamate residue. Guided by the structural results, NMR methods were used to test hypotheses regarding the enzyme mechanism of SSAT. The activity of the enzyme over a range of solution conditions, and towards different polyamine substrates, was determined; the effects of mutating single amino acids in the enzyme were also evaluated. The enzyme appeared to be most active between pH 8.5 and 9.5, and mutation of the aforementioned glutamate significantly altered this behavior. This suggests the glutamate is directly involved in the acetyltransfer reaction, where it likely functions as a catalytic base though the proton relay in the enzyme active site. These studies advance our general understanding of how polyamines are regulated in mammalian cells, and have the potential to assist in developing new therapeutic options for human diseases involving polyamines.text
32
Niemand, Jandeli. "Biochemical characterisation of putrescine and spermidine uptake as a potential therapeutic target against the human malaria parasite, Plasmodium falciparum." Thesis, 2012. http://hdl.handle.net/2263/24986.
Повний текст джерелаАнотація:
Plasmodium falciparum causes the most severe form of human malaria, and the continual development of resistance of this parasite to current anti-malarial drugs underpins a pressing need for the discovery of novel chemotherapeutic approaches. Polyamines and their biosynthetic enzymes are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of the malaria parasite’s polyamine biosynthesis pathway causes cytostatic arrest in the trophozoite stage, but does not cure infections in vivo. This may be due to the salvage of exogenous polyamines from the host, replenishing the intracellular polyamine pool; however the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study the uptake of the polyamines putrescine and spermidine into P. falciparum-infected erythrocytes (iRBC) well as into P. falciparum parasites functionally isolated from their host cell by saponin-permeabilisation of the erythrocyte membrane was investigated using radioisotope flux techniques. While the characteristics of transport of putrescine into infected erythrocytes were similar to those of transport into uninfected erythrocytes, spermidine entered iRBC in part via the ‘new permeation pathways’ induced by the parasite in the erythrocyte membrane. Both putrescine and spermidine were taken up across the plasma membrane of isolated parasites via a saturable, temperature-dependent process that showed competition between different polyamines as well as the polyamine precursor ornithine and basic amino acids. Inhibition of polyamine biosynthesis led to increased total uptake of both putrescine and spermidine. The influx of putrescine and spermidine into isolated parasites was independent of Na+ but increased with increasing pH and showed a marked dependence on the membrane potential, decreasing with membrane depolarisation and increasing with membrane hyperpolarisation. Both anthracene and polyamine derivatives have been shown to have anti-malarial activity. Anthracene-polyamine conjugates have been developed with the aim of utilising the polyamine uptake mechanisms of cancer cells to deliver the cytotoxic anthracene moieties to these cells. Here, several anthracene-polyamine conjugates showed promising anti-malarial activity. These compounds inhibited parasite proliferation with IC50 values in the nM range, and caused an arrest in the cell cycle, as well as a decrease in the mitochondrial membrane potential. Cytotoxicity could not be reversed by the addition of exogenous polyamines, nor did the conjugates have an effect on intracellular polyamine levels. This doctoral study showed that P. falciparum parasites not only synthesise polyamines, but can also acquire putrescine and spermidine from the extracellular environment and paves the way for interfering with polyamine metabolism as an anti-parasitic strategy.Thesis (PhD)--University of Pretoria, 2012.
Biochemistry
unrestricted