subject:(Ras)

Universidad de Cantabria

1. García Ibáñez, Yaiza. Ras site-specific effects in thyroid cáncer.

Degree: 2019, Universidad de Cantabria

► RESUMEN: El oncógeno RAS, frecuentemente mutado en cáncer de tiroides, está presente en diferentes localizaciones celulares, como en las balsas lipídicas (BL) o en membrana… (more)

Subjects/Keywords: RAS

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APA (6^th Edition):

García Ibáñez, Y. (2019). Ras site-specific effects in thyroid cáncer. (Doctoral Dissertation). Universidad de Cantabria. Retrieved from http://hdl.handle.net/10902/16358

Chicago Manual of Style (16^th Edition):

García Ibáñez, Yaiza. “Ras site-specific effects in thyroid cáncer.” 2019. Doctoral Dissertation, Universidad de Cantabria. Accessed February 27, 2021. http://hdl.handle.net/10902/16358.

MLA Handbook (7^th Edition):

García Ibáñez, Yaiza. “Ras site-specific effects in thyroid cáncer.” 2019. Web. 27 Feb 2021.

Vancouver:

García Ibáñez Y. Ras site-specific effects in thyroid cáncer. [Internet] [Doctoral dissertation]. Universidad de Cantabria; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10902/16358.

Council of Science Editors:

García Ibáñez Y. Ras site-specific effects in thyroid cáncer. [Doctoral Dissertation]. Universidad de Cantabria; 2019. Available from: http://hdl.handle.net/10902/16358

Tampereen ammattikorkeakoulu

2. Honkonen, Elina. Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa.

Degree: 2016, Tampereen ammattikorkeakoulu

URL: http://www.theseus.fi/handle/10024/116113

►

Aivoverenkiertohäiriö (AVH) on yleinen sairaus Suomessa. Sairauden aiheuttamat oireet vaikeuttavat kävelyä ja kuntoutumisessa kävelyn uudelleen oppimisella onkin tärkeä merkitys. AVH-potilaat hyötyvät intensiivisestä kävelyharjoittelusta. Opinnäytetyön tarkoituksena… (more)

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Aivoverenkiertohäiriö (AVH) on yleinen sairaus Suomessa. Sairauden aiheuttamat oireet vaikeuttavat kävelyä ja kuntoutumisessa kävelyn uudelleen oppimisella onkin tärkeä merkitys. AVH-potilaat hyötyvät intensiivisestä kävelyharjoittelusta. Opinnäytetyön tarkoituksena oli jäsentää tutkittua ja kokemusperäistä tietoa musiikin käytöstä AVH-potilaan kävelyharjoittelussa. Opinnäytetyötä ohjasivat seuraavat tutkimuskysymykset: Miten musiikki tukee AVH-potilaan kävelyn uudelleen oppimista? Minkälaista musiikkia kannattaa valita AVH-potilaan kävelytaidon edistämiseen? Miten fysioterapeutti voisi hyödyntää musiikkia käytännön tilanteissa? Opinnäytetyön tavoitteena oli rohkaista fysioterapeutteja ja fysioterapeuttiopiskelijoita musiikin käyttöön AVH-potilaan kävelyharjoittelussa. Toiminnallisen opinnäytetyön tiedonhaun menetelminä käytimme kuvailevaa kirjallisuuskatsausta ja teemahaastattelua. Toteutuksena oli opetustilanne Tampereen ammattikorkeakoulun fysioterapeuttiopiskelijoille musiikin mahdollisuuksista AVH-potilaan kävelyharjoittelussa. Opinnäytetyön teoriaosuudessa aiheenamme olivat AVH, kävely ja sen erityispiirteet AVH-potilaalla sekä musiikin vaikutus ihmiseen. Musiikin laaja-alainen aktivointi aivoissa edistää AVH-potilaan hermoverkoston korjaantumista ja luo näin suotuisat edellytykset kävelykyvyn parantumiselle. Tulosten tarkastelussa vastasimme tutkimuskysymyksiimme tarkastelemiemme neljäntoista tutkimuksen sekä neljän teemahaastattelun perusteella. Tutkimusten mukaan musiikin käyttö kävelyharjoittelussa parantaa AVH-potilaan askelrytmiä, askelpituutta, kävelynopeutta ja kävelyn symmetriaa sekä tasapainoa. Musiikin on hyvä olla tempoltaan AVH-potilaan sen hetkisen askelrytmin mukaista, rytmiä esille tuovaa sekä potilaalle tuttua ja mielekästä. Kuitenkin jo pelkkä metronomin tikitys tuottaa vastetta. Harjoitteissa edetään musiikin kuuntelusta ja sen rytmin tunnustelusta AVH-potilaan kävelyharjoitteisiin hänen fysioterapeuttisten tavoitteidensa mukaisesti. Toimenpide-ehdotuksena rohkaisemme tieteellisen ja kokemusperäisen tiedon valossa fysioterapeutteja toteuttamaan musiikillista kävelyharjoittelua. Myös kävelykestävyyttä voisi lisätä pidempikestoisen soittolistan käytöllä, jossa olisi asiakkaan askelrytmiin suhteutettua tempollista vaihtelevuutta. Jatkossa voisi tutkia musiikin vaikutusta AVH-potilaiden kävelyssä ilmenevien erityispiirteiden muuttumiseen.

The purpose of this study was to gather analysed scientific and experiential knowledge on music aided gait training individuals with stroke. The objective of this study was to encourage physiotherapists and physiotherapy students to utilize music in gait training among patients with stroke. The approach of this study functional and both descriptive literature review and interview method were applied. It contains a report and a lesson at Tampere University of Applied Sciences on the topic of this thesis. The data was gathered by theme interviews (n=4) and international researches (n=15). The findings indicate that music can improve stoke…

Advisors/Committee Members: Tampereen ammattikorkeakoulu.

Subjects/Keywords: RAS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Honkonen, E. (2016). Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa. (Thesis). Tampereen ammattikorkeakoulu. Retrieved from http://www.theseus.fi/handle/10024/116113

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Honkonen, Elina. “Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa.” 2016. Thesis, Tampereen ammattikorkeakoulu. Accessed February 27, 2021. http://www.theseus.fi/handle/10024/116113.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Honkonen, Elina. “Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa.” 2016. Web. 27 Feb 2021.

Vancouver:

Honkonen E. Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa. [Internet] [Thesis]. Tampereen ammattikorkeakoulu; 2016. [cited 2021 Feb 27]. Available from: http://www.theseus.fi/handle/10024/116113.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Honkonen E. Musiikin mahti - askelille tahti : Musiikin mahdollisuuksia aivoverenkiertohäiriöpotilaan kävelyharjoittelussa. [Thesis]. Tampereen ammattikorkeakoulu; 2016. Available from: http://www.theseus.fi/handle/10024/116113

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

3. Smith, Russell S. A Novel Affinity Reagent To RAS Perturbs Its Function In Cells.

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21928

► RAS GTPases are mutated to the constitutively active state in around 30% of human cancers. These mutations lock RAS in a GTP-bound ‘active’ state and… (more)

▼ RAS GTPases are mutated to the constitutively active state in around 30% of human cancers. These mutations lock RAS in a GTP-bound ‘active’ state and lead to excessive and inappropriate activation of the pro-proliferative MEK/ERK pathway and pro-survival AKT pathway, both of which are markers of poor prognosis in human cancer. This has made discovery of RAS inhibitors a top priority of cancer research. However, due to its picomolar affinity for GTP and lack of deep binding pockets on its surface, RAS inhibitors have proven elusive, with previous attempts to isolate direct inhibitors of RAS falling short of the mark. Thus there are currently no RAS-inhibitors available in the clinic. Here I describe a monobody affinity reagent that binds to H-RAS and K-RAS, but not N-RAS, with nanomolar affinity resulting in potent inhibition of RAS-driven signaling, oncogenic transformation and tumor growth. NS1 primarily elicits these effects by binding to the α4-β6-α5 interface of RAS, thereby preventing RAS dimerization at the plasma membrane. This in turn blocks the ability of RAS to promote dimerization of RAF, a requirement for RAF activation. However, NS1 elicits isoform-specific effects on RAS in addition to blocking RAS dimerization. For example, NS1 reduces K-RAS association with the plasma membrane and interaction with RAF. Neither of these effects were observed with the H-RAS. Finally, NS1 also reduces the pool of wild type RAS that is GTP-loaded, without blocking nucleotide cycling in vitro. Structural studies suggest that these additional inhibitory effects are the result of NS1 protruding towards to the plasma membrane and altering the orientation or interaction of RAS with the plasma membrane. This work demonstrates the utility of targeting the α4-β6-α5 interface for blocking RAS function and outlines a promising region of RAS to target with therapeutics. Advisors/Committee Members: O'Bryan, John P (advisor), McLachlan, Alan (committee member), Karginov, Andrei (committee member), Tyner, Angela L (committee member), Grippo, Paul J (committee member), O'Bryan, John P (chair).

Subjects/Keywords: NS1 monobody; H-RAS; K-RAS; RAS chimera; RAS inhibitor; RAS dimerization; RAS nanoclustering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Smith, R. S. (2017). A Novel Affinity Reagent To RAS Perturbs Its Function In Cells. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21928

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Smith, Russell S. “A Novel Affinity Reagent To RAS Perturbs Its Function In Cells.” 2017. Thesis, University of Illinois – Chicago. Accessed February 27, 2021. http://hdl.handle.net/10027/21928.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Smith, Russell S. “A Novel Affinity Reagent To RAS Perturbs Its Function In Cells.” 2017. Web. 27 Feb 2021.

Vancouver:

Smith RS. A Novel Affinity Reagent To RAS Perturbs Its Function In Cells. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10027/21928.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Smith RS. A Novel Affinity Reagent To RAS Perturbs Its Function In Cells. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/21928

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

4. Cantu, Daniel Vincenzo. Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance.

Degree: MS, Biophysics, 2019, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1557171451783892

► For over 30 years, Ras GTPases have been intensively studied in cancer research. Membrane bound Ras proteins (H-Ras, N-Ras, K-Ras 4A, and K-Ras 4B)… (more)

▼ For over 30 years, Ras GTPases have been intensively studied in cancer research. Membrane bound Ras proteins (H-Ras, N-Ras, K-Ras 4A, and K-Ras 4B) function as a molecular switch that cycles between GDP “off” state and GTP “on” state. They regulate a diverse array of cellular pathways including proliferation, differentiation, and survival. Oncogenic Ras proteins are found in about 30% of all recorded cancer cases. K-Ras is the highest mutated Ras recorded than all other isoform at 85%. With also a 95% occurrence in pancreatic cancers, discovery for anti-Ras therapeutic strategies have been a highly sought out interest in cancer research. However, despite the research history and high presence in tumors, there is no effective cancer treatment for oncogenic Ras cases. failure to find any treatment is why Ras has been deemed the “undruggable” protein. Contributing to the little success is that Ras is considered to have a relatively smooth and static surface from X-ray crystal structures. Over 140 crystal structures of Ras are deposited in PDB to date. These crystal structure shows minimal global change in residue position, indicating no plausible allosteric binding site. However, two important loop regions, named Switch I and Switch II, are highly dynamic and may adopt multiple confirmations. These loops regions can adopt an ensemble of excited-state confirmations that X-ray crystallography could not detect. Therefore, if there is an allosteric pocket for drug targets, the pocket would exist in an excited-state conformation. Nuclear Magnetic Resonance (NMR) has the ability to detect protein dynamics in sparsely populated excited states. We can utilize the potential of NMR to study a wide range of dynamics at atomic resolution in order to monitor the perturbations in the switch loops, then compare these perturbations between wild-type and mutant K-Ras. Here, I discuss preliminary NMR analysis of both GDP and GTP-bound WT K-Ras and the shortcomings on why traditional NMR methods are not viable to study the switch loops. I will also discuss alternative perspectives using novel NMR techniques to further understand how switch I and II behavior modulate K-Ras intrinsic dynamics and how mutations perturb such dynamics. Advisors/Committee Members: Bruschweiler, Rafael (Advisor).

Subjects/Keywords: Biophysics; Ras, K-Ras, NMR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cantu, D. V. (2019). Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1557171451783892

Chicago Manual of Style (16^th Edition):

Cantu, Daniel Vincenzo. “Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance.” 2019. Masters Thesis, The Ohio State University. Accessed February 27, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1557171451783892.

MLA Handbook (7^th Edition):

Cantu, Daniel Vincenzo. “Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance.” 2019. Web. 27 Feb 2021.

Vancouver:

Cantu DV. Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance. [Internet] [Masters thesis]. The Ohio State University; 2019. [cited 2021 Feb 27]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1557171451783892.

Council of Science Editors:

Cantu DV. Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance. [Masters Thesis]. The Ohio State University; 2019. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1557171451783892

5. Jiménez Gómez, Iñaki. Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals.

Degree: 2017, Universidad de Cantabria

URL: http://hdl.handle.net/10902/12370

► RESUMEN: Las células transforman constantemente los estímulos recibidos del entorno en respuestas biológicas. Este proceso, está mediado por multitud de reacciones químicas en cadena. La… (more)

Subjects/Keywords: Ras

…HVR Región hipervariable de Ras IF Inmunofluorescencia Ig… …Kinase supressor of Ras LB Medio de Luria-‐Bertani LPA… …Fosfatasa Kappa R2B RPTPs subtipo IIb RBD Ras Binding Domain… …o dominio de unión a Ras REM Ras Exchange Motif rpm… …8 2.4.-‐ RUTA DE SEÑALIZACIÓN RAS-‐ERK…

12 more images…

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APA (6^th Edition):

Jiménez Gómez, I. (2017). Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals. (Doctoral Dissertation). Universidad de Cantabria. Retrieved from http://hdl.handle.net/10902/12370

Chicago Manual of Style (16^th Edition):

Jiménez Gómez, Iñaki. “Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals.” 2017. Doctoral Dissertation, Universidad de Cantabria. Accessed February 27, 2021. http://hdl.handle.net/10902/12370.

MLA Handbook (7^th Edition):

Jiménez Gómez, Iñaki. “Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals.” 2017. Web. 27 Feb 2021.

Vancouver:

Jiménez Gómez I. Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals. [Internet] [Doctoral dissertation]. Universidad de Cantabria; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10902/12370.

Council of Science Editors:

Jiménez Gómez I. Ras en el Complejo de Golgi : señales antitumorales mediadas por PTPK: Ras at Golgi Complex: PTPK-mediated antitumor signals. [Doctoral Dissertation]. Universidad de Cantabria; 2017. Available from: http://hdl.handle.net/10902/12370

University of Manchester

6. Vo, Uybach. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.

Degree: 2015, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:261055

►

Ras proteins are mutated in 30% of all human tumours contributing to several malignant phenotypes including abnormal cell growth, proliferation and apoptosis. The activity of… (more)

▼

Ras proteins are mutated in 30% of all human tumours contributing to several malignant phenotypes including abnormal cell growth, proliferation and apoptosis. The activity of Ras is controlled by the inter-conversion between GTP- and GDP- bound forms. This conversion is partly regulated by the binding of protein Son of Sevenless (Sos), a guanine nucleotide exchange factor. The mechanism of Ras activation via its interactions with Sos remains unclear making it challenging as an effective drug target. The aim of this work is to use Nuclear Magnetic Resonance (NMR) spectroscopy and other biophysical methods to understand the molecular activation of Ras via its interactions with Sos. In this thesis, the backbone and Cβ, as well as the partial side-chain NMR assignment for human K-Ras•GDP were completed at pH 7.4. We also revealed significant chemical shift differences between apo, GDP and GTPϒS-bound H-Ras states from the TROSY spectra. In addition, the monitoring of shift perturbations for H-Ras reveals several residues that appear to be central in Sos binding and may provide a starting point in the search for possible inhibition sites for future drug design. To gain a further understanding into the binding events of the Ras:Sos complex, we have expressed and purified the Sos construct containing the REM and Cdc25 domains (SosCat) for titration studies. Here, we have implemented a relatively novel approach to study large complexes (Stoffregen et al. 2012), by selectively labelling the [13C-] Met and Ile methyl groups of SosCat. This approach has provided an assignment for eight reporter signals. In addition, monitoring the shift perturbations of Met [13C-] methyls in the NMR spectra allowed us to examine individual residues at the two Ras binding sites (allosteric and catalytic sites) of SosCat. Disruption of H-Ras•GTPγS binding at the allosteric site (via SosCat W729E mutant) significantly weakens the interactions of Ras at the catalytic site. The data suggests a positive co-operative binding mechanism between the allosteric and catalytic sites, which is consistent with the allosteric feedback model. We have also measured the binding affinities of SosCat (by NMR spectroscopy and fluorescence) with wild type and Ras mutants using different GTP analogues. Our 15N-relaxation data of the H-Ras•GTPϒS:SosCat complex reveal dynamical changes in several regions of Ras other than the P-loop, switch I and II regions. In addition, the backbone NMR relaxation studies revealed that a complex between H-Ras•GTPϒS and SosCat proteins is dynamic and transiently formed. The reported work could be a significant step towards understanding the activation of Ras via its interactions with Sos; and in time the data may influence new anti-cancer treatments.

The Ras family of small GTPases, which includes three isoforms; H-Ras, K-Ras and N-Ras, forms one of the most important nodal points in pathways targeted intensively in cancer drug discovery. These proteins are ubiquitously expressed in mammalian cells and regulate cell signalling…

Advisors/Committee Members: WALTHO, JONATHAN JP, Waltho, Jonathan, Golovanov, Alexander.

Subjects/Keywords: Ras; Sos

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vo, U. (2015). Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:261055

Chicago Manual of Style (16^th Edition):

Vo, Uybach. “Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.” 2015. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:261055.

MLA Handbook (7^th Edition):

Vo, Uybach. “Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.” 2015. Web. 27 Feb 2021.

Vancouver:

Vo U. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. [Internet] [Doctoral dissertation]. University of Manchester; 2015. [cited 2021 Feb 27]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:261055.

Council of Science Editors:

Vo U. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. [Doctoral Dissertation]. University of Manchester; 2015. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:261055

University of Manchester

7. Vo, Uybach. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.

Degree: PhD, 2015, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/biochemical-and-biophysical-studies-to-characterise-the-rassosnucleotide-interactions(691827f9-00d8-445a-ab3f-e5b236f918ba).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706236

► Ras proteins are mutated in 30% of all human tumours contributing to several malignant phenotypes including abnormal cell growth, proliferation and apoptosis. The activity of… (more)

▼ Ras proteins are mutated in 30% of all human tumours contributing to several malignant phenotypes including abnormal cell growth, proliferation and apoptosis. The activity of Ras is controlled by the inter-conversion between GTP- and GDP- bound forms. This conversion is partly regulated by the binding of protein Son of Sevenless (Sos), a guanine nucleotide exchange factor. The mechanism of Ras activation via its interactions with Sos remains unclear making it challenging as an effective drug target. The aim of this work is to use Nuclear Magnetic Resonance (NMR) spectroscopy and other biophysical methods to understand the molecular activation of Ras via its interactions with Sos. In this thesis, the backbone and Cβ, as well as the partial side-chain NMR assignment for human K-Ras•GDP were completed at pH 7.4. We also revealed significant chemical shift differences between apo, GDP and GTPϒS-bound H-Ras states from the TROSY spectra. In addition, the monitoring of shift perturbations for H-Ras reveals several residues that appear to be central in Sos binding and may provide a starting point in the search for possible inhibition sites for future drug design. To gain a further understanding into the binding events of the Ras:Sos complex, we have expressed and purified the Sos construct containing the REM and Cdc25 domains (SosCat) for titration studies. Here, we have implemented a relatively novel approach to study large complexes (Stoffregen et al. 2012), by selectively labelling the [13C-] Met and Ile methyl groups of SosCat. This approach has provided an assignment for eight reporter signals. In addition, monitoring the shift perturbations of Met [13C-] methyls in the NMR spectra allowed us to examine individual residues at the two Ras binding sites (allosteric and catalytic sites) of SosCat. Disruption of H-Ras•GTPγS binding at the allosteric site (via SosCat W729E mutant) significantly weakens the interactions of Ras at the catalytic site. The data suggests a positive co-operative binding mechanism between the allosteric and catalytic sites, which is consistent with the allosteric feedback model. We have also measured the binding affinities of SosCat (by NMR spectroscopy and fluorescence) with wild type and Ras mutants using different GTP analogues. Our 15N-relaxation data of the H-Ras•GTPϒS:SosCat complex reveal dynamical changes in several regions of Ras other than the P-loop, switch I and II regions. In addition, the backbone NMR relaxation studies revealed that a complex between H-Ras•GTPϒS and SosCat proteins is dynamic and transiently formed. The reported work could be a significant step towards understanding the activation of Ras via its interactions with Sos; and in time the data may influence new anti-cancer treatments.

Subjects/Keywords: 616.99; Ras; Sos

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vo, U. (2015). Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/biochemical-and-biophysical-studies-to-characterise-the-rassosnucleotide-interactions(691827f9-00d8-445a-ab3f-e5b236f918ba).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706236

Chicago Manual of Style (16^th Edition):

Vo, Uybach. “Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.” 2015. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. https://www.research.manchester.ac.uk/portal/en/theses/biochemical-and-biophysical-studies-to-characterise-the-rassosnucleotide-interactions(691827f9-00d8-445a-ab3f-e5b236f918ba).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706236.

MLA Handbook (7^th Edition):

Vo, Uybach. “Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions.” 2015. Web. 27 Feb 2021.

Vancouver:

Vo U. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. [Internet] [Doctoral dissertation]. University of Manchester; 2015. [cited 2021 Feb 27]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/biochemical-and-biophysical-studies-to-characterise-the-rassosnucleotide-interactions(691827f9-00d8-445a-ab3f-e5b236f918ba).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706236.

Council of Science Editors:

Vo U. Biochemical and biophysical studies to characterise the Ras:Sos:nucleotide interactions. [Doctoral Dissertation]. University of Manchester; 2015. Available from: https://www.research.manchester.ac.uk/portal/en/theses/biochemical-and-biophysical-studies-to-characterise-the-rassosnucleotide-interactions(691827f9-00d8-445a-ab3f-e5b236f918ba).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706236

NSYSU

8. Cho, Chun-yu. Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK.

Degree: Master, Institute of Biomedical Sciences, 2006, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721106-102443

► Many tumor suppressor genes are known to be inactivated by epigenetic modifications including DNA methylation and histone deacetylation. RECK is a membrane-anchored glycoprotein that may… (more)

Subjects/Keywords: Ras; RECK

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cho, C. (2006). Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721106-102443

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cho, Chun-yu. “Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK.” 2006. Thesis, NSYSU. Accessed February 27, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721106-102443.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cho, Chun-yu. “Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK.” 2006. Web. 27 Feb 2021.

Vancouver:

Cho C. Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK. [Internet] [Thesis]. NSYSU; 2006. [cited 2021 Feb 27]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721106-102443.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cho C. Involvement of DNA methylation in ras-induced down-regulation of the metastasis suppressor RECK. [Thesis]. NSYSU; 2006. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721106-102443

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ruhr Universität Bochum

9. Neumann, Sebastian. Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1).

Degree: 2011, Ruhr Universität Bochum

URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31305

► Eine erhöhte intrazelluläre freie Calcium-Ionen-Konzentration induziert den programmierten Zelltod, die Apoptose. In dieser Arbeit führte die Transfektion mit Calciumphosphat/DNA-Nanopartikeln nur zu einem geringen Anstieg der… (more)

Subjects/Keywords: Nanopartikel; Calcium; Ras; Protektion; Transvektion

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APA (6^th Edition):

Neumann, S. (2011). Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1). (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31305

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Neumann, Sebastian. “Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1).” 2011. Thesis, Ruhr Universität Bochum. Accessed February 27, 2021. http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31305.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Neumann, Sebastian. “Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1).” 2011. Web. 27 Feb 2021.

Vancouver:

Neumann S. Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1). [Internet] [Thesis]. Ruhr Universität Bochum; 2011. [cited 2021 Feb 27]. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31305.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Neumann S. Zelluläre Protektion bei Transfektion mit Calciumphosphat/DNA-Nanopartikeln und durch Regulation des voltage-dependent anion channel-1 (VDAC-1). [Thesis]. Ruhr Universität Bochum; 2011. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31305

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ruhr Universität Bochum

10. Güldenhaupt, Jörn. ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras.

Degree: 2010, Ruhr Universität Bochum

URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-32311

► Das Ras Protein gehört zur Familie der kleinen GTPasen und ist ein protoonkogenes Protein, das in 20% aller Tumore mutiert ist. In vivo ist Ras… (more)

Subjects/Keywords: Proteine; Ras; Guanosintriphosphatasen; Lipidmembran; Infrarotspektroskopie

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APA (6^th Edition):

Güldenhaupt, J. (2010). ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-32311

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Güldenhaupt, Jörn. “ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras.” 2010. Thesis, Ruhr Universität Bochum. Accessed February 27, 2021. http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-32311.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Güldenhaupt, Jörn. “ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras.” 2010. Web. 27 Feb 2021.

Vancouver:

Güldenhaupt J. ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras. [Internet] [Thesis]. Ruhr Universität Bochum; 2010. [cited 2021 Feb 27]. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-32311.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Güldenhaupt J. ATF-FTIR-spektroskopische Untersuchungen von membrangebundenem Ras. [Thesis]. Ruhr Universität Bochum; 2010. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-32311

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ruhr Universität Bochum

11. Karassek, Sascha. Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose.

Degree: 2010, Ruhr Universität Bochum

URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-29769

► In der vorliegenden Arbeit wurde der Einfluss von Rheb auf die stressinduzierte Apoptose in verschiedenen zellulären Systemen untersucht. Dabei konnte gezeigt werden, dass eine exogene… (more)

Subjects/Keywords: RAS; Apoptosis; Proteinbiosynthese; Rab-Proteine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Karassek, S. (2010). Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-29769

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Karassek, Sascha. “Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose.” 2010. Thesis, Ruhr Universität Bochum. Accessed February 27, 2021. http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-29769.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Karassek, Sascha. “Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose.” 2010. Web. 27 Feb 2021.

Vancouver:

Karassek S. Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose. [Internet] [Thesis]. Ruhr Universität Bochum; 2010. [cited 2021 Feb 27]. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-29769.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Karassek S. Einfluss der kleinen GTPase Ras homologue enriched in brain (Rheb) auf die stressinduzierte Apoptose. [Thesis]. Ruhr Universität Bochum; 2010. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-29769

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Dalhousie University

12. Arsenault, Daniel. The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells.

Degree: MS, Department of Biochemistry & Molecular Biology, 2012, Dalhousie University

URL: http://hdl.handle.net/10222/15710

► Phosphatidylcholine (PC) is an essential component of biological membranes and is synthesized by the CDP-choline pathway under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase-alpha… (more)

Subjects/Keywords: H-ras; Anoikis; Phosphatidylcholine; Cancer

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APA (6^th Edition):

Arsenault, D. (2012). The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/15710

Chicago Manual of Style (16^th Edition):

Arsenault, Daniel. “The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells.” 2012. Masters Thesis, Dalhousie University. Accessed February 27, 2021. http://hdl.handle.net/10222/15710.

MLA Handbook (7^th Edition):

Arsenault, Daniel. “The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells.” 2012. Web. 27 Feb 2021.

Vancouver:

Arsenault D. The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells. [Internet] [Masters thesis]. Dalhousie University; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10222/15710.

Council of Science Editors:

Arsenault D. The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells. [Masters Thesis]. Dalhousie University; 2012. Available from: http://hdl.handle.net/10222/15710

Oregon State University

13. Cheng, Ronshan. Ras oncogenes and p53 suppressor genes in fish carcinogenesis models.

Degree: PhD, Food Science and Technology, 1995, Oregon State University

URL: http://hdl.handle.net/1957/27187

► A digoxigenin-labeled nonradioactive detection system was used to screen a zebrafish cDNA library for p53-like and ras-like genes. One clone was isolated and identified as… (more)

▼ A digoxigenin-labeled nonradioactive detection system was used to screen a zebrafish cDNA library for p53-like and ras-like genes. One clone was isolated and identified as an incomplete p53-like gene. The insert size of this clone is 1777 bp, which encodes part of evolutionarily conserved region II and all of regions III, IV, and V. A magnetically enriched whole zebrafish cDNA library was constructed to enhance possible recovery of ras-like genes in zebrafish. One clone, termed Zras-Bl, carried an insert of 2592 bp with an open reading frame encoding a 188 amino acid residue ras p21 protein. Based on total protein sequence, this expressed zebrafish ras p21 is most closely related to human N-ras (91% homology), with lesser homology to Ha-ras (84%) and Ki-ras (85%). Preliminary partial sequence data obtained by genomic and reverase transcriptasepolymerase chain reaction (RT-PCR) screening indicate the presence of at least one additional expressed ras gene in zebrafish. The tumorigenicity and Ki-ras mutational properties of dietary 7,12-dimethylbenz[a]anthracene (DMBA) and dibenzo[a,l]pyrene (DBP) were compared in rainbow trout. Both chemicals elicited predominantly 12(1)G->A and 12(2)G->T mutations in trout liver tumors. Two {12(1)G->T and 12(2)G->T} and one {12(1)G->A and 12(2)G->T} double mutation were also observed in DBP livers tumors, but not in DMBA liver tumors. Some stomach tumors from both chemicals exhibited so much DNA degradation that routine PCR amplification was not possible. Among sixteen DMBA stomach tumors with intact DNA, no Ki-ras mutations were found. Of sixteen DBP stomach tumors examined, one had 12(1)G->A and two had 13(1)G->C mutations. The observed G->T transversions are compatible with apurinic mutagenesis driven by unstable DNA adducts arising from one-electron oxidation, but this is not true for the major G->A transitions or G->C transversions and rare double mutations found in this study. The low sensitivity of direct sequencing may limit the frequency of ras mutant detection in this study. Advisors/Committee Members: Bailey, George S. (advisor).

Subjects/Keywords: Ras oncogenes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cheng, R. (1995). Ras oncogenes and p53 suppressor genes in fish carcinogenesis models. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/27187

Chicago Manual of Style (16^th Edition):

Cheng, Ronshan. “Ras oncogenes and p53 suppressor genes in fish carcinogenesis models.” 1995. Doctoral Dissertation, Oregon State University. Accessed February 27, 2021. http://hdl.handle.net/1957/27187.

MLA Handbook (7^th Edition):

Cheng, Ronshan. “Ras oncogenes and p53 suppressor genes in fish carcinogenesis models.” 1995. Web. 27 Feb 2021.

Vancouver:

Cheng R. Ras oncogenes and p53 suppressor genes in fish carcinogenesis models. [Internet] [Doctoral dissertation]. Oregon State University; 1995. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1957/27187.

Council of Science Editors:

Cheng R. Ras oncogenes and p53 suppressor genes in fish carcinogenesis models. [Doctoral Dissertation]. Oregon State University; 1995. Available from: http://hdl.handle.net/1957/27187

Oregon State University

14. Liang, Xiaoshan. Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure.

Degree: PhD, Biochemistry and Biophysics, 1993, Oregon State University

URL: http://hdl.handle.net/1957/36253

► Characterization of the 5' flanking region of rainbow trout ki-ras gene was begun with the cloning and sequencing of this region by the inverse PCR… (more)

▼ Characterization of the 5' flanking region of rainbow trout ki-ras gene was begun with the cloning and sequencing of this region by the inverse PCR technique and dideoxynucleotide chain termination method. In total, a nucleotide sequence of 1080 bp upstream from the first coding ATG was sequenced. Although this region showed certain promoter elements, it does not share common features with other mammalian ras promoters, which lack the TATA and contain multiple GC boxes with Spl binding activities. In contrast, this region in trout ras contains typical TATA and CCAAT boxes. This structural difference of the trout ki-ras promoter from that of other mammalian ras genes may suggest that different transcriptional regulation mechanisms of the ras ger.e are used at various levels in evolution. The chromatin structure of the trout ki-ras gene was studied by probing invivo for DNase I hypersensitive sites. To overcome the difficulties of using the traditional indirect end labeling method for a single-copy gene, the technique of ligation-mediated PCR was applied. No hypersensitive sites were observed at or near the codon 12 region of the gene, either in normal (protooncogene) or tumor (oncogene) tissue from the liver. This result suggests that the local chromatin structure of trout ki-ras gene may not be an important factor for codon 12 mutations induced by genotoxins, and that changes of chromatin structure are unlikely to be promoted after tumor formation. Studies by micrococcal nuclease demonstrate that this ras gene, in the region around 12, lacks ordered nucleosome positioning or may be even free of nucleosomes. Such an irregular organization of ras oncogenic chromatin would resemble that of many other "normal", highly active eukaryotic genes. The intrinsic affinity of trout ki-ras gene for aflatoxin B₁ was determined by in vitro alkylation experiments. Exon 1 of the gene was synthesized and labeled at the 5'end of the coding strand by the PCR technique. Taking advantage of the selective cleavage of AFB1-DNA adducts by piperidine under alkali conditions, the frequency of AFB 1 attack to each guanyl site was determined by densitometric scans after the cleaved fragments were electrophoresed on sequencing gels. The results demonstrated that two guanyl sites of codon 12 had differential affinity to AFBl, the more 5' G was relatively inaccessible but the more 3' G was accessible, indicating that the sequence selectivity of AFB I may contribute to the preference of the initial adduction in vivo. Advisors/Committee Members: van Holde, Kensal E. (advisor), Bailey, George (committee member).

Subjects/Keywords: Ras oncogenes

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APA (6^th Edition):

Liang, X. (1993). Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/36253

Chicago Manual of Style (16^th Edition):

Liang, Xiaoshan. “Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure.” 1993. Doctoral Dissertation, Oregon State University. Accessed February 27, 2021. http://hdl.handle.net/1957/36253.

MLA Handbook (7^th Edition):

Liang, Xiaoshan. “Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure.” 1993. Web. 27 Feb 2021.

Vancouver:

Liang X. Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure. [Internet] [Doctoral dissertation]. Oregon State University; 1993. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1957/36253.

Council of Science Editors:

Liang X. Studies of rainbow trout Ki-ras gene : sequencing, aflatoxin B1 binding, and chromatin structure. [Doctoral Dissertation]. Oregon State University; 1993. Available from: http://hdl.handle.net/1957/36253

Vanderbilt University

15. Burns, Michael Charles. Small Molecule Modulation of the Ras-SOS Interaction in Cancer.

Degree: PhD, Biochemistry, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/15156

► Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing… (more)

▼ Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. This dissertation describes the discovery of small molecules that can both inhibit and activate SOS-catalyzed Ras activation. Chapter II describes small molecules that bind directly to Ras that inhibit SOS-catalyzed nucleotide exchange on Ras in a competitive manner. Chapter III describes an investigation examining small molecules that activate SOS-catalyzed nucleotide exchange in vitro and modulate Ras signaling pathways in cells. This study has revealed valuable tool compounds that alter the Ras-SOS interaction by binding to a previously uncharacterized small molecule binding site on the Ras:SOS:Ras complex. X-ray crystallography of Ras:SOS:Ras in complex with these molecules revealed that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. Treating cells with these compounds resulted in an increase in Ras-GTP levels and disruption of MAPK and PI3K signaling at low micromolar concentrations. Chapter IV describes efforts to improve these molecules by conducting a high-throughput screen of the VICB library, and Chapter V describes ongoing investigations into the possible mechanisms of action underlying the perturbed signaling observed downstream of Ras following compound treatment. Chapter VI includes a discussion of the work conducted in this dissertation and describes future directions based on this work. These small molecules represent new tools to study the acute activation of Ras and form the basis for a new approach to target Ras in cancer. Advisors/Committee Members: Scott Hiebert (committee member), Lawrence Marnett (committee member), Jennifer Pietenpol (committee member), Stephen W. Fesik (Committee Chair).

Subjects/Keywords: Ras; SOS; nucleotide exchange

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Burns, M. C. (2014). Small Molecule Modulation of the Ras-SOS Interaction in Cancer. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15156

Chicago Manual of Style (16^th Edition):

Burns, Michael Charles. “Small Molecule Modulation of the Ras-SOS Interaction in Cancer.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed February 27, 2021. http://hdl.handle.net/1803/15156.

MLA Handbook (7^th Edition):

Burns, Michael Charles. “Small Molecule Modulation of the Ras-SOS Interaction in Cancer.” 2014. Web. 27 Feb 2021.

Vancouver:

Burns MC. Small Molecule Modulation of the Ras-SOS Interaction in Cancer. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1803/15156.

Council of Science Editors:

Burns MC. Small Molecule Modulation of the Ras-SOS Interaction in Cancer. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/15156

Universidade de Brasília

16. Larissa Fernandes. Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis.

Degree: 2007, Universidade de Brasília

URL: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2591

►

Paracoccidioides brasiliensis é um fungo termo-dimórfico que causa uma micose sistêmica de alta incidência na América Latina. Devido sua participação no controle de morfogênese, diferenciação… (more)

▼

Paracoccidioides brasiliensis é um fungo termo-dimórfico que causa uma micose sistêmica de alta incidência na América Latina. Devido sua participação no controle de morfogênese, diferenciação e virulência em patógenos, decidiu-se caracterizar os genes ras em P. brasiliensis. Foram identificados ras1 e ras2 que codificam para duas proteínas diferentes com alta identidade. O padrão transcricional de ras também foi investigado por RT-PCR durante a transição micélio para levedura (M→Y), choque térmico a 42C e após internalização de leveduras em macrófagos murinos. Ambos os genes foram regulados negativamente em leveduras internalizadas em macrófagos e ras1 foi modulado negativamente a 42C. Entretanto, os genes ras não apresentaram variação transcricional durante a transição M→Y. O fato de que as proteínas Ras são localizadas na membrana através de farnesilação, permitiu a análise in silico dos genes que codificam para as subunidades das preniltransferases (farnesiltransferase e geranilgeraniltransferase I): ram1, ram2 e cdc43. P. brasiliensis apresenta em seu genoma todos os genes necessários para maquinaria de prenilação. Um inibidor de farnesiltransferase foi utilizado para investigar a importância desse processo no crescimento vegetativo e transição dimórfica. O bloqueio da farnesilação interferiu com o crescimento vegetativo de leveduras e estimulou a produção de tubos germinativos mesmo a 37C. Durante a transição Y→M, o inibidor aumentou a filamentação de maneira dosedependente, indicando que o bloqueio da farnesilação favorece a forma miceliana de P. brasiliensis. Os resultados sugerem que os genes ras devem ter um papel no dimorfismo, resposta a choque térmico e na interação patógeno-hospedeiro. Uma estratégia para estudar a função de ras1 em P. brasiliensis também foi desenhada através de interferência no RNA. Cassetes de silenciamento com ras1 senso e antisenso foram construídos para futura investigação detalhada do papel dos genes ras na patobiologia deste fungo.

Paracoccidioides brasiliensis is a thermo-dimorphic fungus that causes a human systemic mycosis with high incidence in Latin America. Due to their participation in the control of pathogen morphogenesis, differentiation and virulence the characterization of ras genes in P. brasiliensis was done. It was identified ras1 and ras2 coding for two different proteins with high identity. The ras transcriptional pattern was investigated by RT-PCR during mycelium-to-yeast (M→Y) transition, heat shock at 42C and after internalization of yeast cells by murine macrophages. Both genes were down regulated inside macrophages and ras1, at 42C. In contrast, the ras genes did not show any transcriptional variation during the M→Y transition. The fact that Ras proteins are attached to the membrane via farnesylation prompted the search on Pb gene database for the genes coding the subunits of the prenyltransferases (farnesyltransferase and geranilgeraniltransferase I): ram1, ram2 and cdc43. P. brasiliensis has all genes necessary to the…

Advisors/Committee Members: Marcelo Afonso Vallim, Lidia Maria Pepe de Moraes, Francisco Rogerio Fontenele Aragão, Maria Sueli Soares Felipe.

Subjects/Keywords: BIOLOGIA MOLECULAR; ras; paracoccidioides brasiliensis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fernandes, L. (2007). Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis. (Thesis). Universidade de Brasília. Retrieved from http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2591

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fernandes, Larissa. “Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis.” 2007. Thesis, Universidade de Brasília. Accessed February 27, 2021. http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2591.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fernandes, Larissa. “Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis.” 2007. Web. 27 Feb 2021.

Vancouver:

Fernandes L. Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis. [Internet] [Thesis]. Universidade de Brasília; 2007. [cited 2021 Feb 27]. Available from: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2591.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fernandes L. Caracterização molecular e funcional dos genes ras1 e ras2 do fungo dimórfico e patogênico Paracoccidioides Brasiliensis. [Thesis]. Universidade de Brasília; 2007. Available from: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2591

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

17. Ducioame, Alexa Rene. Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations.

Degree: MS, Civil Engineering, 2018, University of North Dakota

URL: https://commons.und.edu/theses/2201

► The Tongue River in Cavalier has experienced severe erosion and bank failures in recent years. Two homes have been evacuated and demolished, and another… (more)

▼ The Tongue River in Cavalier has experienced severe erosion and bank failures in recent years. Two homes have been evacuated and demolished, and another lost ten ft of their yard overnight when a tree slumped into the river. The city lies downstream of Renwick Dam and nine other dams upstream of it which have greatly reduced the average flows through town. The resulting lowered water surface is a probable source of the streambank instability. A series of rock weirs was proposed to be installed in town to raise the minimum water surface elevation and potentially provide benefit to all problem sites identified in town. The existing conditions and several potential weir locations were analyzed using the Hydrologic Engineering Center River Analysis System (HEC-RAS) sediment transport analysis. The Park Street weir location was chosen as optimal for maximizing benefit at all problem sites, minimizing scour, and addressing the most urgent needs. The Red River Riparian Project team originally identified twenty problem sites in town that needed attention. Since then, several of the locations have installed projects to protect the streambanks. Three potential weir locations were identified for this study: Woodland Terrace, Park Street, and Division Ave. The Woodland Terrace site is immediately downstream of the last original problem site. However, that site and the next upstream of it have had projects constructed. The Park Street weir is immediately downstream of the last problem site that has had no remediation. The Division Ave location is closer to the area where more severe erosion was occurring and houses needed to be removed. The existing conditions unsteady flow model geometry was created using LiDAR, survey, and other available data. Hydrology was developed with a U.S. Army Corps of Engineers (USACE) Hydrologic Engineering Center Hydrologic Modeling System (HEC-HMS) model of the Pembina River watershed and U.S. Geological Survey (USGS) gage data. Then the unsteady flow model was calibrated to 2013 flow and elevation data. The sediment transport model used the gradation data collected at the time of survey, USGS gage data, and several assumed parameters. The results do not precisely model actual erosion and deposition depths due to these assumptions and some software limitations. This study compares potential project impacts from each weir location. The parameters stay the same across all models and a preferred option can be selected by a relative comparison. The results can be verified with more detailed data and modeling in the future. Advisors/Committee Members: Yeo H. Lim.

Subjects/Keywords: Cavalier; HEC-RAS; Hydraulic; Sediment

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APA (6^th Edition):

Ducioame, A. R. (2018). Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations. (Masters Thesis). University of North Dakota. Retrieved from https://commons.und.edu/theses/2201

Chicago Manual of Style (16^th Edition):

Ducioame, Alexa Rene. “Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations.” 2018. Masters Thesis, University of North Dakota. Accessed February 27, 2021. https://commons.und.edu/theses/2201.

MLA Handbook (7^th Edition):

Ducioame, Alexa Rene. “Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations.” 2018. Web. 27 Feb 2021.

Vancouver:

Ducioame AR. Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations. [Internet] [Masters thesis]. University of North Dakota; 2018. [cited 2021 Feb 27]. Available from: https://commons.und.edu/theses/2201.

Council of Science Editors:

Ducioame AR. Evaluation Of Streambank Stabilization Options On The Tongue River In Cavalier, ND Utilizing Hec-Ras Hydraulic And Sediment Transport Simulations. [Masters Thesis]. University of North Dakota; 2018. Available from: https://commons.und.edu/theses/2201

University of Ottawa

18. McDonell, Laura Marie. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .

Degree: 2018, University of Ottawa

URL: http://hdl.handle.net/10393/37610

► Ras-MAPK signalling regulates key cellular processes such as proliferation, differentiation and survival. Unsurprisingly, mutations in RAS genes are now recognized as potent oncogenic drivers. However,… (more)

▼ Ras-MAPK signalling regulates key cellular processes such as proliferation, differentiation and survival. Unsurprisingly, mutations in RAS genes are now recognized as potent oncogenic drivers. However, disruption of this pathway during development is associated with a family of disorders termed the Rasopathies. Shared clinical features include cutaneous, neurological and cardiac anomalies. At the outset of this study, the genetic etiology of three neurocutaneous disorders, microcephaly-capillary malformation syndrome (MIC-CAP), encephalocraniocutaneous lipomatosis (ECCL) and PHACE (Posterior fossa malformations, facial Hemangiomas, cerebral Arterial anomalies, Cardiovascular defects and Eye abnormalities) syndrome had not yet been established. This thesis identifies mutations in STAM-binding protein (STAMBP) in a cohort of individuals with MIC-CAP syndrome using whole-exome sequencing (WES). This gene encodes a deubiquitinating isopeptidase that regulates cell surface receptor-mediated endocytosis and sorting. Cell lines of individuals with MIC-CAP show reduced STAMBP expression, associated with accumulation of ubiquitinated protein aggregates, increased apoptosis and constitutive activation of the Ras-MAPK and PI3K-AKT pathways. WES also enabled the identification of post-zygotic mutations within the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1) in individuals with ECCL. Fibroblasts from affected individuals showed increased phosphorylation of the FGFRs consistent with receptor activation as well as insensitive signal transduction through the Ras-MAPK pathway. Neurocutaneous syndromes can feature striking vascular lesions such as the cerebral vasculopathy and large segmented facials hemangiomas seen in PHACE syndrome. The asymmetric and patchy vascular malformations coupled with a sporadic incidence and absence of familial recurrence suggested that PHACE might be caused by post-zygotic mutations. Interrogation of a discordant sib-pair using copy number analysis and WES did not identify causative mutations indicating the need for a comprehensive and targeted –omic approach to elucidate the molecular mechanism of this syndrome. Taken together, these findings expand the spectrum of the Rasopathies while providing novel pathomechanistic insights into the regulation of cellular proliferation and survival during development.

Subjects/Keywords: Ras-Mapk Signalling; Neurocutaneous Disorders

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APA (6^th Edition):

McDonell, L. M. (2018). Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McDonell, Laura Marie. “Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .” 2018. Thesis, University of Ottawa. Accessed February 27, 2021. http://hdl.handle.net/10393/37610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McDonell, Laura Marie. “Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .” 2018. Web. 27 Feb 2021.

Vancouver:

McDonell LM. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . [Internet] [Thesis]. University of Ottawa; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10393/37610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McDonell LM. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Oregon State University

19. Mangold, Kathy A. Characterization of a ras gene in rainbow trout.

Degree: PhD, Toxicology, 1989, Oregon State University

URL: http://hdl.handle.net/1957/38435

► The rainbow trout (Oncorhynchus mykiss) model of chemical carcinogenesis is becoming increasingly important as a supplement to rodent studies. However, much of the molecular biology… (more)

▼ The rainbow trout (Oncorhynchus mykiss) model of chemical carcinogenesis is becoming increasingly important as a supplement to rodent studies. However, much of the molecular biology of the carcinogenic response is still unknown in the trout model. The ras gene family has been implicated in the tumorigenesis of both spontaneous and chemically-induced tumors in mammals. This study is the first to characterize a ras proto-oncogene in rainbow trout. To accomplish this, the ras gene sequence was amplified in vitro by using polymerase chain reaction (PCR). Two synthetic and degenerative oligonucleotide sequences based on a consensus mammal/goldfish ras sequence were used as primers in the PCR procedure. An 800 base pair (bp) sequence was amplified from trout genomic DNA and hybridized with a human c-Ha-ras sequence. The initial amplifications of trout liver cDNA using the PCR procedure with the synthetic ras primers resulted in a single product of approximately 216 bps. However, this amplified "trout" 216 by product was subsequently shown to be an artifact of carryover from a human Ki-ras plasmid. Carryover is a common problem found in many laboratories involved with the PCR procedure, and extensive precautions were used to eliminate the problem in our laboratories. The 800 by PCR product was cloned and sequenced using Taq polymerase. RT-8, a clone containing the 800 bp insert, was shown to have 91% homology to the first two exons of mammalian c-Ha-ras gene and lesser homology to other ras genes. Amplification of trout liver cDNA using specific primers based on the RT-8 sequence resulted in the amplification of sequences identical to the sequence of the RT-8 insert without an intron, as well as unique sequences, which may represent additional trout ras genes. The PCR procedure was modified to identify sequence information immediately 3' of the known trout ras sequence. Partial sequences of at least two different trout ras genes are presented. With this new information, analysis of DNA sequence information from chemically initiated tumors may elucidate the role activation of ras genes plays in the trout model of carcinogenesis. Advisors/Committee Members: Bailey, George S. (advisor).

Subjects/Keywords: Ras oncogenes

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APA (6^th Edition):

Mangold, K. A. (1989). Characterization of a ras gene in rainbow trout. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/38435

Chicago Manual of Style (16^th Edition):

Mangold, Kathy A. “Characterization of a ras gene in rainbow trout.” 1989. Doctoral Dissertation, Oregon State University. Accessed February 27, 2021. http://hdl.handle.net/1957/38435.

MLA Handbook (7^th Edition):

Mangold, Kathy A. “Characterization of a ras gene in rainbow trout.” 1989. Web. 27 Feb 2021.

Vancouver:

Mangold KA. Characterization of a ras gene in rainbow trout. [Internet] [Doctoral dissertation]. Oregon State University; 1989. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1957/38435.

Council of Science Editors:

Mangold KA. Characterization of a ras gene in rainbow trout. [Doctoral Dissertation]. Oregon State University; 1989. Available from: http://hdl.handle.net/1957/38435

University of Melbourne

20. Banerjee, Sangita. Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours.

Degree: 2015, University of Melbourne

URL: http://hdl.handle.net/11343/58834

► Cancer is a cooperative process, involving mutations in multiple genes. Activation of a cancer-driving gene, the Ras small GTPase, via a mutation that locks Ras… (more)

Subjects/Keywords: cancer; autophagy; Ras; Drosophila

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APA (6^th Edition):

Banerjee, S. (2015). Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/58834

Chicago Manual of Style (16^th Edition):

Banerjee, Sangita. “Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours.” 2015. Masters Thesis, University of Melbourne. Accessed February 27, 2021. http://hdl.handle.net/11343/58834.

MLA Handbook (7^th Edition):

Banerjee, Sangita. “Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours.” 2015. Web. 27 Feb 2021.

Vancouver:

Banerjee S. Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours. [Internet] [Masters thesis]. University of Melbourne; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11343/58834.

Council of Science Editors:

Banerjee S. Cooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours. [Masters Thesis]. University of Melbourne; 2015. Available from: http://hdl.handle.net/11343/58834

University of Melbourne

21. Sannang, Rowena Tenri. Suppressors of oncogenic Cbl in the Drosophila eye.

Degree: 2018, University of Melbourne

URL: http://hdl.handle.net/11343/218164

► Cbl is an E3 ligase, and downregulates several cellular signalling pathways, in this role by targeting receptor tyrosine kinases for endocytosis. Mammalian Cbl was first… (more)

▼ Cbl is an E3 ligase, and downregulates several cellular signalling pathways, in this role by targeting receptor tyrosine kinases for endocytosis. Mammalian Cbl was first identified as the full-length isoform of v-Cbl, a C-terminal truncated dominant negative oncogene that permits binding of v-Cbl to Cbl targets but does not facilitate their ubiquitination. This results in constitutive activation of the receptor tyrosine kinase. In this thesis, I used a Drosophila analogue of v-Cbl, named Dv-cbl. GMR>Dv-cbl had been used prior to the commencement of this study to screen for modifiers of its rough and overgrown eye phenotype using the Gene search system, a transposon-based inducible expression system. In this study, a subset of the suppressors of the GMR>Dvcbl phenotype from that screen, and two other representative lines were further investigated. The published interactions and functions of the genes implicated by the GS lines are discussed and a method of suppression of the GMR>Dv-cbl phenotype by each line is suggested. In the published work presented in this thesis, the Akap200 expressing lines EP2254 and GS2208 were further studied. Expression of Akap200 in EP2254 was confirmed via mRNA in situ hybridisation, and its ability to also suppress the Ras85DV12 phenotype was confirmed. The ability of EP2254 to suppress GMR-Dv-cbl and sev-Ras85DV12 coexpression was confirmed. When GMR-Dv-cbl and sev-Ras85DV12 are coexpressed, a phenotype that is greater than the cumulative phenotype of each would suggest arises. In fact, GMR-Dvcbl (where Dv-cbl was directly driven from the GMR promoter) was used instead of GMR-Gal4, UAS-Dv-cbl (GMR>Dv-cbl) as the coexpression of GMR>Dv-cbl and sev- Ras85DV12 results in lethality, and coexpression of GMR-Dv-cbl and sev-Ras85DV12 did not. Alone, each has a mildly rough eye. I showed that EP2254 was able to suppress this phenotype and that this suppression was partially independent of apoptosis. The endogenous function of Akap200 in the Drosophila eye was then investigated. An mRNA in situ hybridisation experiment showed that endogenous Akap200 is present in the eye disc, and a series of immunohistochemical stains showed that Akap200 was expressed in a subset of photoreceptor cells. Knockdown of Akap200 using RNAi lines showed that endogenous Akap200 was having a modifying effect on the GMR>Dv-cbl phenotype, as knockdown of Akap200 enhances the GMR>Dv-cbl phenotype. A recent study suggests that Notch is protected from internalisation by Cbl by Akap200, which is consistent with the results in this thesis.

Subjects/Keywords: Drosophila; Cbl; Ras; Akap200; oncogene

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sannang, R. T. (2018). Suppressors of oncogenic Cbl in the Drosophila eye. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/218164

Chicago Manual of Style (16^th Edition):

Sannang, Rowena Tenri. “Suppressors of oncogenic Cbl in the Drosophila eye.” 2018. Masters Thesis, University of Melbourne. Accessed February 27, 2021. http://hdl.handle.net/11343/218164.

MLA Handbook (7^th Edition):

Sannang, Rowena Tenri. “Suppressors of oncogenic Cbl in the Drosophila eye.” 2018. Web. 27 Feb 2021.

Vancouver:

Sannang RT. Suppressors of oncogenic Cbl in the Drosophila eye. [Internet] [Masters thesis]. University of Melbourne; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11343/218164.

Council of Science Editors:

Sannang RT. Suppressors of oncogenic Cbl in the Drosophila eye. [Masters Thesis]. University of Melbourne; 2018. Available from: http://hdl.handle.net/11343/218164

Universitat de Valencia

22. Lara Valencia, Paola Fernanda. Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico.

Degree: 2015, Universitat de Valencia

URL: http://hdl.handle.net/10550/52521

► El melanoma, es la neoplasia cutánea mas agresiva cuya incidencia y mortalidad han incrementado de manera espectacular en las últimas décadas. La patogénesis del melanoma… (more)

▼ El melanoma, es la neoplasia cutánea mas agresiva cuya incidencia y mortalidad han incrementado de manera espectacular en las últimas décadas. La patogénesis del melanoma es compleja y no se comprende totalmente; para su desarrollo es necesaria la transformación maligna de melanocitos, que ocurre tanto en individuos genéticamente normales como genéticamente predispuestos. Las alteraciones genéticas identificadas en melanomas en diferentes sitios y con diferentes niveles de exposición al sol indican que hay distintas vías genéticas en el desarrollo de melanoma, una de ellas es la mutación activadora de los genes RAS. El N-RAS se encuentra mutado en aproximadamente el 15-20% de los melanomas primarios cutáneos, observándose algunas carecterísticas histológicas y clínicas relacionadas con esta mutación. Por otro lado, el melanoma es una neoplasia muy inmunogénica, una de las vías implicadas es la vía PD-1/PD-L1. El PD-1, al interactuar con sus ligandos (PD-L1 y PD-L2) envía señales intracelulares que inducen a disminuir la producción de citoquinas proinflamatorias causando efectos en la diferenciación y supervivencia celular por la inhibición temprana de las señales de activación a través del CD28 o de manera indirecta, por medio de IL-2. Tanto el CD28 como la IL-2 promueven la expansión y supervivencia natural a través de efectos antiapoptóticos sobre el ciclo celular y sobre la activación de los genes de citoquinas, beneficiadose las células tumorales para evadir la respuesta del sistema inmune, permitiendo su supervivencia y crecimiento. Objetivos generales: 1- Determinar si el estado mutacional del oncogén N-RAS tiene influencia en el pronóstico de los pacientes con melanoma cutáneo. 2- Establecer la posible asociación de PD-L1 y PD-1 con el estado mutacional de N-RAS y asimismo la influencia de ambos marcadores en la evolución clínica de los pacientes con melanoma cutáneo. Materiales y métodos: Se ha estudiado la mutación del oncogén N-RAS mediante secuenciación de Sanger, asi como el estudio inmunohistoqímico de los anticuerpos PD-1 y PD-L1 en 126 casos diagnosticados de melanoma cutáneo primario, los resultados se correlacionaron con las variables clínicas e histológicas para establecer signifancia estadística con los factores pronósticos. Advisors/Committee Members: Monteagudo Castro, Carlos (advisor).

Subjects/Keywords: Melanoma; Mutación N-RAS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lara Valencia, P. F. (2015). Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico. (Doctoral Dissertation). Universitat de Valencia. Retrieved from http://hdl.handle.net/10550/52521

Chicago Manual of Style (16^th Edition):

Lara Valencia, Paola Fernanda. “Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico. ” 2015. Doctoral Dissertation, Universitat de Valencia. Accessed February 27, 2021. http://hdl.handle.net/10550/52521.

MLA Handbook (7^th Edition):

Lara Valencia, Paola Fernanda. “Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico. ” 2015. Web. 27 Feb 2021.

Vancouver:

Lara Valencia PF. Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico. [Internet] [Doctoral dissertation]. Universitat de Valencia; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10550/52521.

Council of Science Editors:

Lara Valencia PF. Estado mutacional del oncogén N-RAS en melanoma cutáneo como factor pronóstico. Estudio clínico-patológico. [Doctoral Dissertation]. Universitat de Valencia; 2015. Available from: http://hdl.handle.net/10550/52521

University of Georgia

23. Long, Matthew. Rasul and Nabi.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/23912

► Degrees of prophetic office have been a facet of Islamic discourse since the days of Muhammad’s early community. Are there degrees of prophecy? Are certain… (more)

Subjects/Keywords: RASŪ; L; NABĪ

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APA (6^th Edition):

Long, M. (2014). Rasul and Nabi. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/23912

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Long, Matthew. “Rasul and Nabi.” 2014. Thesis, University of Georgia. Accessed February 27, 2021. http://hdl.handle.net/10724/23912.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Long, Matthew. “Rasul and Nabi.” 2014. Web. 27 Feb 2021.

Vancouver:

Long M. Rasul and Nabi. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10724/23912.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Long M. Rasul and Nabi. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/23912

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

24. Kapatou, Kasiani-Anastasia. Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους.

Degree: 2016, University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας

URL: http://hdl.handle.net/10442/hedi/38332

►

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the fourth most common cause of cancer related death worldwide. Nowadays several… (more)

▼

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the fourth most common cause of cancer related death worldwide. Nowadays several clinical studies have highlighted the predictive role of gene alterations involved in the EGFR pathway. In this study we investigated the presence of KRAS / BRAF mutations and their correlation with the clinical-histopathological parameters in 322 patients with colon cancer. In addition, we collected fresh paired tumor and normal tissue from 50 patients and investigated the expression level of KRAS and EGFR gene, in mRNA transcripts using the method of real time polymerase chain reaction. Then the correlation between expression levels and various clinicopathological parameters was examined.Our study showed that frequency and distribution of KRAS and BRAF mutations in Greek population are similar to that described in previous studies. G>A transition at codon 12 of KRAS gene showed a statistically significant correlation with the absence of lymph node metastases (p<0.05). Instead, G>C transversion in the same codon, showed statistically significant correlation with the presence of lymph node metastases (p<0.005). KRAS/ BRAF p.V600E mutations were correlated with tumour location in the right colon compared to those located in the left colon and rectum (p<0.05, p<0.005 respectively). There was statistically significant correlation between the absence of KRAS mutations and high grade tumors (p<0.005).The presence of BRAF p.V600E mutation was associated with high grade tumors (p<0.005) and increased number of lymph node metastasis (N2), in patients with metastatic disease (p<0.05).According to absolute quantification method mRNA expression of KRAS/EGFR genes was higher in tumour compared to normal tissue and this finding was statistically significant (p<0.05). Among patients with lymph node involvement, mRNA expression of KRAS gene was significantly associated with the number of lymph node metastasis. We also found a positive correlation between increased mRNA expression of the EGF-receptor and the presence of the KRAS gene mutations, but not proved to be statistically significant, possibly due to small number of patients.In summary our findings confirm that tumours with right location follow different pathway of carcinogenesis compared to left located tumours. Moreover, the presence of KRAS/BRAF mutations was associated with aggressive behavior and worse survival of patients with colorectal adenocarcinomas. KRAS mRNA expression could be a candidate biomarker for assessing invasive capacity of the tumor and possible recurrence of the disease. Increased mRNA expression of the EGF-receptor in patients with KRAS mutations indicates the presence of other regulatory mechanisms beyond KRAS mutations. Assessment of expression levels may serve as a useful biomarker of prognostic and predictive value in the future.

O καρκίνος του παχέος εντέρου αποτελεί την τρίτη συχνότερη μορφή καρκίνου και την τέταρτη σε συχνότητα αιτία θανάτου από καρκίνο παγκοσμίως. Τελευταία, πλήθος…

Subjects/Keywords: EGFR έκφραση; Σηματοδοτικό μονοπάτι RAS / RAF / MEK / ERK; RAS έκφραση; EGFR expression; RAS expression; signaling of RAS/RAF/MEK/ERK

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APA (6^th Edition):

Kapatou, K. (2016). Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους. (Thesis). University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας. Retrieved from http://hdl.handle.net/10442/hedi/38332

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kapatou, Kasiani-Anastasia. “Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους.” 2016. Thesis, University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας. Accessed February 27, 2021. http://hdl.handle.net/10442/hedi/38332.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kapatou, Kasiani-Anastasia. “Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους.” 2016. Web. 27 Feb 2021.

Vancouver:

Kapatou K. Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους. [Internet] [Thesis]. University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10442/hedi/38332.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kapatou K. Μελέτη της έκφρασης των γονιδίων EGFR, RAS που εμπλέκονται στο μονοπάτι μεταγωγής σήματος του υποδοχέα του επιδερμικού αυξητικού παράγοντα σε συμπαγείς όγκους. [Thesis]. University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας; 2016. Available from: http://hdl.handle.net/10442/hedi/38332

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Alberta

25. Mattar, Christine. Variable lipidation of Ras isoforms directs their differential membrane association.

Degree: MS, Department of Biochemistry, 2000, University of Alberta

URL: https://era.library.ualberta.ca/files/9z9031792

Subjects/Keywords: Ras proteins.; Ras oncogenes.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mattar, C. (2000). Variable lipidation of Ras isoforms directs their differential membrane association. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/9z9031792

Chicago Manual of Style (16^th Edition):

Mattar, Christine. “Variable lipidation of Ras isoforms directs their differential membrane association.” 2000. Masters Thesis, University of Alberta. Accessed February 27, 2021. https://era.library.ualberta.ca/files/9z9031792.

MLA Handbook (7^th Edition):

Mattar, Christine. “Variable lipidation of Ras isoforms directs their differential membrane association.” 2000. Web. 27 Feb 2021.

Vancouver:

Mattar C. Variable lipidation of Ras isoforms directs their differential membrane association. [Internet] [Masters thesis]. University of Alberta; 2000. [cited 2021 Feb 27]. Available from: https://era.library.ualberta.ca/files/9z9031792.

Council of Science Editors:

Mattar C. Variable lipidation of Ras isoforms directs their differential membrane association. [Masters Thesis]. University of Alberta; 2000. Available from: https://era.library.ualberta.ca/files/9z9031792

Vilnius University

26. Sužiedėlis, Kęstutis. Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui.

Degree: Review of scientific papers submitted for habilitation procedure, Biochemistry, 2009, Vilnius University

URL: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20090305_110424-90379 ;

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Vienas esminių gyvybės bruožų – gebėjimas prisitaikyti prie kintančių aplinkos sąlygų. Dėl aplinkos poveikio kinta tiek prokariotiniai, tiek vienaląsčiai ir daugialąsčiai eukariotiniai organizmai, todėl nenuostabu,… (more)

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Vienas esminių gyvybės bruožų – gebėjimas prisitaikyti prie kintančių aplinkos sąlygų. Dėl aplinkos poveikio kinta tiek prokariotiniai, tiek vienaląsčiai ir daugialąsčiai eukariotiniai organizmai, todėl nenuostabu, kad tam tikri gyvų ląstelių pasitelkiami atsako į aplinką ar poveikį būdai yra universalūs. Vienas tokių universalių su atsaku į aplinką susijusių reiškinių yra signalinių molekulių ir signalo perdavimo kelių egzistavimas įvairiausiose gyvybės formose, nuo bakterijų iki žinduolių ląstelių. Signalo perdavimo sistemos elementai kinta signalo perdavimo metu, todėl, analizuojant signalo perdavimo kelių elementus – signalines molekules, galima įvertinti ar ląstelė „pajuto“ aplinkos poveikį, ar aktyvintos atsako į poveikį sistemos. Taigi signalo perdavimo elementų analizė gali būti naudojama kaip ląstelės atsako į poveikį vertinimo įrankis. Šioje apžvalgoje nagrinėjama: • Eukariotų signalinių kelių komponentai – Ras šeimos baltymų funkcijos mejozėje; • Prokariotų signalinių kelių komponentai – bakterijų atsako į rūgštinį aplinkos stresą sistema; • Sutrikusių funkcijų (vėžinių) ląstelių atsakas į taikomą terapiją – signalinių elementų atsako į terapiją vertinimui paieška; • Signalinių kelių komponentų tyrimai pogenominėje eroje – kokybiškai naujas tyrimų etapas. Išvados 1. MAPK – universalus Ras aktyvinamo ląstelių dalijimosi signalinio kelio komponentas pagal kurio fosforilinimo laipsnį galima spręsti apie ląstelių aktyvinimą dalijimuisi; 2. asr RNR – universalus... [toliau žr. visą tekstą]

One of the fundamental features of the live species is the ability to adapt to the changing environment. Both prokaryotes and eukaryotes change due to the environmental stress, therefore it is obvious, that common mechanisms to cope the environmental stresses are universal among all the live organisms. One of such universal mechanisms related to the environmental stresses – signal transduction pathways and signal molecules existing among all kingdoms of live species. Elements of signal transduction systems change during the signal transduction, therefore the analysis of signal molecules allows the evaluation of the state of cellular response and the analysis of signaling elements could be employed as a tool to evaluate the cellular response. Following topics are discussed in this review: • Components of eukaryotic signal transduction system – function of Ras proteins in meiosis; • Components of prokaryotic signal transduction system – components of bacterial response to acid stress; • Response to the used therapy of transformed cells – search for the signal elements to evaluate the response to therapy; • Investigations of signal transduction components in post genomic era – qualitatively new stage of investigations. Conclusions 1. MAPK is a universal component of Ras signal transduction pathway to evaluate, according to the stage of phosphorylation of MAPK, the activation of the cell for division 2. asr RNA is a universal component of adaptation of enterobacteria to... [to full text]

Subjects/Keywords: Aplinkos poveikis; Signalo perdavimas; Ras; Environmental stress; Signal transduction; Ras

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sužiedėlis, Kęstutis. (2009). Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui. (Thesis). Vilnius University. Retrieved from http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20090305_110424-90379 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sužiedėlis, Kęstutis. “Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui.” 2009. Thesis, Vilnius University. Accessed February 27, 2021. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20090305_110424-90379 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sužiedėlis, Kęstutis. “Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui.” 2009. Web. 27 Feb 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

Sužiedėlis, Kęstutis. Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui. [Internet] [Thesis]. Vilnius University; 2009. [cited 2021 Feb 27]. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20090305_110424-90379 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sužiedėlis, Kęstutis. Signalinių kelių tyrimai ląstelių atsako į aplinkos poveikį vertinimui. [Thesis]. Vilnius University; 2009. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20090305_110424-90379 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Lithuanian University of Agriculture

27. Jonušaitis, Karolis. Reguliuoto upelio ruožo hidrodinaminis modeliavimas.

Degree: Master, Environmental Engineering and Land Management, 2011, Lithuanian University of Agriculture

URL: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20110607_115053-48393 ;

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Baigiamąjame darbe analizuojama galimybė netradiciniais Lietuvoje metodais (naudojant hidraulinį modelį) įvertinti reguliuoto upelio deformacijų įtaką jo pralaidumui, kadangi dažnai atsitinka taip, kad numatomos nemažos lėšos… (more)

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Baigiamąjame darbe analizuojama galimybė netradiciniais Lietuvoje metodais (naudojant hidraulinį modelį) įvertinti reguliuoto upelio deformacijų įtaką jo pralaidumui, kadangi dažnai atsitinka taip, kad numatomos nemažos lėšos remontui, kai tuo tarpu upelio pralaidumo charakteristikos dar pakankamai geros. Modelio kalibravimui ir hidrauliniam modeliavimui naudojami realiai išmatuoti ir projektiniai duomenys. Hidrodinaminis modelis sudaromas tuo tikslu, kad būtų galima patikrinti pasirinkto upelio ruožo vagos ir tame ruože esančios pralaidos matmenis kaip pakraštines sąlygas, naudojant iš projekto paimtais hidrologiniais skaičiavimais nustatytus debitus ir įvertinti tėkmės sąlygas esant projektinėms geometrinėms charakteristikoms ir realiai išmatuotoms dabartinėje upelio būklėje. Atliekant natūrinius tyrimus buvo nustatinėjamos šios reguliuoto upelio charakteristikos: debitas, vandens lygiai, vandens paviršiaus nuolydis, šiurkštumo koeficientai; griovyje esančių pralaidų būklė. Darbo tikslas - panaudojant programą HEC-RAS sukurti pasirinkto reguliuoto upelio ruožo hidrodinaminį modelį ir patikrinti griovio ir pralaidos pralaidumo pokyčius lyginant projektinius ir natūroje išmatuotus parametrus. Tyrimo uždaviniai: 1. Literatūros apžvalgoje išnagrinėti atvirų vagų hidraulinio modeliavimo metodus, programinę įrangą ir praktinio taikymo atvejus. 2. Išmokti dirbti su programine įranga HEC-RAS. 3. Sukurti pasirinkto upelio ruožo hidrodinaminį modelį ir atlikti modeliavimą. 4. Pagal... [toliau žr. visą tekstą]

Final work analyzes the possibility to evaluate the impact of deformations of regulated stream on its capacity by the methods that are non-traditional in Lithuania (using a hydraulic model), as often is the case when substantial funding is provided for repair, while the stream capacity characteristics are still good enough. The actual measured and projected data is used for model calibration and hydraulic modelling. Creation of hydrodynamic model aims to verify the dimensions of bed and culverts in the selected stream section using the discharges based on the project hydrological calculations as peripheral conditions and to evaluate the flow conditions at the projected geometric characteristics and at those measured in the current state of the stream. Field research determined the following characteristics of the stream: yield, water levels, water surface slope, roughness coefficients; condition of the equipment in the ditch: state of culverts. Aim of the work – by modelling the established flow to determine the longitudinal water level profiles for the both cases and to evaluate the differences. Results of the work allow stating that lateral trench deformations have negligible impact on the flow conditions. Objectives of the research: 1. to analyze the hydraulic modelling techniques of open beds, software and cases of practical application; 2. to learn working with the software HEC-RAS; 3. to create hydrodynamic model of the selected stream section and to perform simulations... [to full text]

Advisors/Committee Members: Dumbrauskas, Antanas (Master’s thesis supervisor), Povilaitis, Arvydas (Master’s thesis reviewer), Misevičienė, Stefanija (Master’s thesis reviewer), Sivickis, Kazys (Master’s degree committee chair), Dumbrauskas, Antanas (Master’s degree committee member), Kinčius, Liudas (Master’s degree committee member), Radzevičius, Algirdas (Master’s degree committee member), Mikuckis, Feliksas (Master’s degree committee member).

Subjects/Keywords: Hidrodinaminis modeliavimas; Reguliuotas; HEC - RAS; Hydrodynamic Modelling; Regulated; HEC -RAS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jonušaitis, Karolis. (2011). Reguliuoto upelio ruožo hidrodinaminis modeliavimas. (Masters Thesis). Lithuanian University of Agriculture. Retrieved from http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20110607_115053-48393 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16^th Edition):

Jonušaitis, Karolis. “Reguliuoto upelio ruožo hidrodinaminis modeliavimas.” 2011. Masters Thesis, Lithuanian University of Agriculture. Accessed February 27, 2021. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20110607_115053-48393 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

MLA Handbook (7^th Edition):

Jonušaitis, Karolis. “Reguliuoto upelio ruožo hidrodinaminis modeliavimas.” 2011. Web. 27 Feb 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

Jonušaitis, Karolis. Reguliuoto upelio ruožo hidrodinaminis modeliavimas. [Internet] [Masters thesis]. Lithuanian University of Agriculture; 2011. [cited 2021 Feb 27]. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20110607_115053-48393 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

Jonušaitis, Karolis. Reguliuoto upelio ruožo hidrodinaminis modeliavimas. [Masters Thesis]. Lithuanian University of Agriculture; 2011. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20110607_115053-48393 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vilnius University

28. Ger, Marija. Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime.

Degree: Dissertation, Biochemistry, 2009, Vilnius University

URL: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112308-72240 ;

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Šiame darbe buvo ištirtas komplekso tarp p120 RasGAP ir adaptorinio baltymo Nck1 susidarymo mechanizmas ir vaidmuo ląstelėje. Mažieji G-baltymai Ras yra svarbūs ląstelės dalijimosi, diferenciacijos… (more)

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Šiame darbe buvo ištirtas komplekso tarp p120 RasGAP ir adaptorinio baltymo Nck1 susidarymo mechanizmas ir vaidmuo ląstelėje. Mažieji G-baltymai Ras yra svarbūs ląstelės dalijimosi, diferenciacijos ir išgyvenimo reguliatoriai. p120 Ras GTPazę aktyvinantis baltymas (p120 RasGAP) yra pagrindinis Ras aktyvumo neigiamas reguliatorius. Šiame darbe buvo nustatyta, jog Nck šeimos adaptoriniai baltymai, Nck1 ir Nck2, sąveikauja su RasGAP. Sąveika nepriklauso nuo trumpalaikio poveikio trombocitų kilmės augimo faktoriumi (PDGF) bei vyksta skirtingo tipo ląstelėse. Baltymai Nck1 ir RasGAP kolokalizuojasi ląstelėje. Už sąveiką su RasGAP yra atsakingi pirmasis ir trečiasis adaptorinio baltymo Nck1 SH3 domenai bei RasGAP N-galinės prolino turtingosios sekos, sąveika gali vykti tiesiogiai. Adaptorinio baltymo Nck1 ir RasGAP kompleksas disocijuoja po adhezinių ląstelių sąveikos su substratu suardymo ir pradeda atsistatyti tik praėjus penkioms valandoms po sąveikos su substratu atstatymo. Už sąveikos suardymą yra atsakingas RasGAP baltymo konformacijos pokytis. Adaptorinio baltymo Nck1 sąveika su RasGAP didina RasGAP katalizinį aktyvumą, o ląstelėje Nck1 perteklinė ekspresija mažina RasGAP reguliuojamą PDGF indukuotą Ras aktyvumą. Nck1 ir RasGAP komplekso disociacija po ląstelių suspendavimo koreliuoja su RasGAP aktyvumo sumažėjimu bei Ras aktyvumo ląstelėje padidėjimu. Gauti duomenys leidžia daryti prielaidą, jog adaptorinis baltymas Nck1 dalyvauja GTPazės Ras aktyvumo reguliavime.

This study was focused on complex between the adaptor protein Nck1 and p120 RasGTPase-activating protein and its role in the cell. The family of small G-proteins Ras are crucial intracellular regulators of growth factor signaling. The main negative regulator of Ras is p120 RasGAP. We have discovered that adaptor proteins Nck1 and Nck2 associate with p120 RasGAP. This interaction does not change upon the short-term stimulation with platelet-derived growth factor BB (PDGF-BB) and is present in various cell lines. By means of confocal microscopy we have shown that Nck1 and p120 RasGAP colocalize in the cell. Using various Nck1 mutants we have elucidated that SH3-I and SH3-III domains of Nck1 associate with N-terminal proline-rich sequence of RasGAP. Nck1 associate with p120 RasGAP directly in vitro. The complex between adaptor protein Nck and RasGAP dissociates after the adherent cell detachment due to unidentified conformational change of p120 RasGAP. Nck1 association with p120 RasGAP increases RasGAP catalytic activity, and overexpression of Nck1 decreases p120 RasGAP-regulated PDGF-BB-induced Ras activation. Accordingly, the dissociation of complex between Nck1 and p120 RasGAP after the cell detachment corellates with the increase in Ras activity. The data reveals a new role of Nck1 adaptor protein as the modulator of Ras activity.

Advisors/Committee Members: Kirvelienė, Vida (Doctoral dissertation committee chair), Mildažienė, Vida (Doctoral dissertation committee member), Kalvelytė, Audronė (Doctoral dissertation committee member), Biziulevičienė, Genė (Doctoral dissertation committee member), Characiejus, Dainius (Doctoral dissertation committee member), Sužiedėlis, Kęstutis (Doctoral dissertation opponent), Skeberdis, Vytenis Arvydas (Doctoral dissertation opponent).

Subjects/Keywords: Proliferacija; Ras; Baltymų sąveika; Proliferation; Ras; Protein-protein interactions

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ger, Marija. (2009). Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime. (Doctoral Dissertation). Vilnius University. Retrieved from http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112308-72240 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16^th Edition):

Ger, Marija. “Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime.” 2009. Doctoral Dissertation, Vilnius University. Accessed February 27, 2021. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112308-72240 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

MLA Handbook (7^th Edition):

Ger, Marija. “Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime.” 2009. Web. 27 Feb 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

Ger, Marija. Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime. [Internet] [Doctoral dissertation]. Vilnius University; 2009. [cited 2021 Feb 27]. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112308-72240 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

Ger, Marija. Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime. [Doctoral Dissertation]. Vilnius University; 2009. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112308-72240 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vilnius University

29. Ger, Marija. The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation.

Degree: PhD, Biochemistry, 2009, Vilnius University

URL: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112319-06660 ;

►

This study was focused on complex between the adaptor protein Nck1 and p120 RasGTPase-activating protein and its role in the cell. The family of small… (more)

▼

This study was focused on complex between the adaptor protein Nck1 and p120 RasGTPase-activating protein and its role in the cell. The family of small G-proteins Ras are crucial intracellular regulators of growth factor signaling. The main negative regulator of Ras is p120 RasGAP. We have discovered that adaptor proteins Nck1 and Nck2 associate with p120 RasGAP. This interaction does not change upon the short-term stimulation with platelet-derived growth factor BB (PDGF-BB) and is present in various cell lines. By means of confocal microscopy we have shown that Nck1 and p120 RasGAP colocalize in the cell. Using various Nck1 mutants we have elucidated that SH3-I and SH3-III domains of Nck1 associate with N-terminal proline-rich sequence of RasGAP. Nck1 associate with p120 RasGAP directly in vitro. The complex between adaptor protein Nck and RasGAP dissociates after the adherent cell detachment due to unidentified conformational change of p120 RasGAP. Nck1 association with p120 RasGAP increases RasGAP catalytic activity, and overexpression of Nck1 decreases p120 RasGAP-regulated PDGF-BB-induced Ras activation. Accordingly, the dissociation of complex between Nck1 and p120 RasGAP after the cell detachment corellates with the increase in Ras activity. The data reveals a new role of Nck1 adaptor protein as the modulator of Ras activity.

Šiame darbe buvo ištirtas komplekso tarp p120 RasGAP ir adaptorinio baltymo Nck1 susidarymo mechanizmas ir vaidmuo ląstelėje. Mažieji G-baltymai Ras yra svarbūs ląstelės dalijimosi, diferenciacijos ir išgyvenimo reguliatoriai. p120 Ras GTPazę aktyvinantis baltymas (p120 RasGAP) yra pagrindinis Ras aktyvumo neigiamas reguliatorius. Šiame darbe buvo nustatyta, jog Nck šeimos adaptoriniai baltymai, Nck1 ir Nck2, sąveikauja su RasGAP. Sąveika nepriklauso nuo trumpalaikio poveikio trombocitų kilmės augimo faktoriumi (PDGF) bei vyksta skirtingo tipo ląstelėse. Baltymai Nck1 ir RasGAP kolokalizuojasi ląstelėje. Už sąveiką su RasGAP yra atsakingi pirmasis ir trečiasis adaptorinio baltymo Nck1 SH3 domenai bei RasGAP N-galinės prolino turtingosios sekos, sąveika gali vykti tiesiogiai. Adaptorinio baltymo Nck1 ir RasGAP kompleksas disocijuoja po adhezinių ląstelių sąveikos su substratu suardymo ir pradeda atsistatyti tik praėjus penkioms valandoms po sąveikos su substratu atstatymo. Už sąveikos suardymą yra atsakingas RasGAP baltymo konformacijos pokytis. Adaptorinio baltymo Nck1 sąveika su RasGAP didina RasGAP katalizinį aktyvumą, o ląstelėje Nck1 perteklinė ekspresija mažina RasGAP reguliuojamą PDGF indukuotą Ras aktyvumą. Nck1 ir RasGAP komplekso disociacija po ląstelių suspendavimo koreliuoja su RasGAP aktyvumo sumažėjimu bei Ras aktyvumo ląstelėje padidėjimu. Gauti duomenys leidžia daryti prielaidą, jog adaptorinis baltymas Nck1 dalyvauja GTPazės Ras aktyvumo reguliavime.

Advisors/Committee Members: Kirvelienė, Vida (Doctoral dissertation committee chair), Mildažienė, Vida (Doctoral dissertation committee member), Kalvelytė, Audronė (Doctoral dissertation committee member), Biziulevičienė, Genė (Doctoral dissertation committee member), Characiejus, Dainius (Doctoral dissertation committee member), Sužiedėlis, Kęstutis (Doctoral dissertation opponent), Skeberdis, Vytenis Arvydas (Doctoral dissertation opponent).

Subjects/Keywords: Proliferation; Ras; Protein-protein interactions; Proliferacija; Ras; Baltymų sąveika

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ger, Marija. (2009). The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation. (Doctoral Dissertation). Vilnius University. Retrieved from http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112319-06660 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16^th Edition):

Ger, Marija. “The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation.” 2009. Doctoral Dissertation, Vilnius University. Accessed February 27, 2021. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112319-06660 ;.

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MLA Handbook (7^th Edition):

Ger, Marija. “The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation.” 2009. Web. 27 Feb 2021.

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Author name may be incomplete

Vancouver:

Ger, Marija. The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation. [Internet] [Doctoral dissertation]. Vilnius University; 2009. [cited 2021 Feb 27]. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112319-06660 ;.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

Ger, Marija. The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation. [Doctoral Dissertation]. Vilnius University; 2009. Available from: http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20091202_112319-06660 ;

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

30. Parker, Jillian Ann. The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting.

Degree: PhD, Department of Chemistry and Chemical Biology, 2017, Northeastern University

URL: http://hdl.handle.net/2047/D20240308

► The small GTPase Ras is a bimolecular switch protein involved in a multitude of cellular signaling pathways, including those that control cell proliferation, differentiation, and… (more)

▼ The small GTPase Ras is a bimolecular switch protein involved in a multitude of cellular signaling pathways, including those that control cell proliferation, differentiation, and apoptosis. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP to GTP in the active site to yield signaling active Ras(GTP), while GTPase activating proteins (GAPs) accelerate the rate of hydrolysis of GTP to GDP on Ras to return the protein to its signaling inactive conformation. The three isoforms of Ras, H-Ras, K-Ras, and N-Ras, share 100% sequence identity in their effector lobes, which contain the active site and switch regions responsible for interactions with effector and regulatory proteins. The C-terminus of Ras is posttranslationally modified for insertion into the plasma membrane, where Ras interacts with a variety of effector proteins, such as Raf, PI3K, and RalGEF. Importantly, residue differences in the allosteric lobe, which is 90% similar among the isoforms, could contribute to isoform-specific Ras-membrane interactions, though this is an understudied area of Ras biology. Additionally, recent reports of dimerization and nanocluster formation at the membrane have emerged as important signaling units of Ras in the cell. The work presented herein provides unique insights into Ras dimerization, with a particular focus on understanding dimerization at a molecular level, and its signaling implications. Further, despite the fact that H-Ras has been used as a model for the other isoforms, we continue to show that K-Ras and N-Ras are structurally, biochemically, and functionally distinct. The first crystal structure of wild-type K-Ras bound to a GTP analogue is presented, along with complementary NMR data to assess this isoforms' unique balance of conformational states in solution. Additionally, a novel co-crystal structure of WT K-Ras and oncogenic K-RasG12D bound to a small protein inhibitor molecule provides unprecedented insight into how to target one of the most prevalent oncogenes in human cancers.

Subjects/Keywords: bimolecular switch proteins; guanine nucleotide exchange factors; Ras isoform; K-Ras

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APA (6^th Edition):

Parker, J. A. (2017). The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20240308

Chicago Manual of Style (16^th Edition):

Parker, Jillian Ann. “The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting.” 2017. Doctoral Dissertation, Northeastern University. Accessed February 27, 2021. http://hdl.handle.net/2047/D20240308.

MLA Handbook (7^th Edition):

Parker, Jillian Ann. “The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting.” 2017. Web. 27 Feb 2021.

Vancouver:

Parker JA. The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting. [Internet] [Doctoral dissertation]. Northeastern University; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2047/D20240308.

Council of Science Editors:

Parker JA. The most oncogenic Ras isoform: specific insights into K-Ras structure, dimerization, and targeting. [Doctoral Dissertation]. Northeastern University; 2017. Available from: http://hdl.handle.net/2047/D20240308

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