Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Laromustine (6)
- Apoptosis (2)
- BAG3 (2)
- Leukemia (2)
- laromustine(VNP40101M) (1)
-
- poly(ADP - ribose) (1)
- polymerase(PARP) (1)
- 2-phenoxyethanol (1)
- Abscisic acid; aleurone; barley; gibberellin; particle bombardment; phosphorylation (1)
- Alanine (1)
- Algal bloom (1)
- Aluminum dosing (1)
- Anticancer (1)
- Archaea (1)
- Athletics (1)
- Biogeochemistry (1)
- Biosynthesis (1)
- Cancer (1)
- Cancer treatment (1)
- Carotenoid (1)
- Carotenoids (1)
- Carvone (1)
- Cell biology (1)
- Cell proliferation (1)
- Chemical genetic screen (1)
- Chemical screen (1)
- Chemotherapy (1)
- Click chemistry (1)
- Cloretazine (1)
- Cortisol (1)
Articles 1 - 14 of 14
Full-Text Articles in Life Sciences
Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, Yuxuan (Nelson) Wu
Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, Yuxuan (Nelson) Wu
Honors Theses
The entrainment map, developed by Dr.Diekman and Dr.Bose, is claimed to be a 1-dimensional map that produces a better prediction for phase-locking than methods than the phase response curve for circadian models. In his paper, he constructs the entrainment map for the two-dimensional circadian model, the Novak-Tyson model, and the other two higher-dimensional circadian models. For this thesis, we concentrate on exploring if it is viable to construct the entrainment map for other circadian models that are not included in his paper: the Becker-Weimann model and the Relogio model. In addition, we discuss the challenges of constructing the entrainment map …
The Quantitative Assessment Of Pond Scum: An Examination Of The Biogeochemistry Of Phosphorus Cycling In The Belgrade Lakes, Abbey M. Sykes
The Quantitative Assessment Of Pond Scum: An Examination Of The Biogeochemistry Of Phosphorus Cycling In The Belgrade Lakes, Abbey M. Sykes
Honors Theses
The internal recycling phosphorus in freshwater lake bottom sediments represents a significant source of hypolimnetic phosphorus (P) release for many of Maine’s lakes. In summer months, Maine lakes often thermally stratify and the lake hypolimnion develops anoxia, leading to a reduction in redox potential at the sediment-water interface. These reducing conditions facilitate the reductive dissolution of ferric iron, and, since phosphorus is often present in freshwater lake sediments as solid FeOOH-PO4 complexes, results in release of soluble phosphorus into the water column. Our current study presents field and laboratory data from sediment fractionation extractions designed to quantify concentrations of …
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Honors Theses
Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …
Identifying Metabolites As Markers Of Fatigue In Athletes, Christopher D. George
Identifying Metabolites As Markers Of Fatigue In Athletes, Christopher D. George
Honors Theses
Fatigue in athletes caused by inadequate rest and other stressors can be severely detrimental to their health, and yet there is no reliable way to measure and track fatigue. Many classical measures of fatigue like body mass and resting heart rate are not reliable ways to track the physical fatigue of an athlete because they can change with many factors. In addition, it is not known how academic stress on top of physical stress affects fatigue. Metabolomics is a relatively new area of study and tracking metabolites offers the possibility to produce biomarkers to assess fatigue. This study collected saliva …
Investigating Phosphorylation Patterns And Their Effect On The Activity Of Transcription Factor Taabf1 In Imbibing Cereal Grains, Grace Uwase
Honors Theses
The wheat transcription factor TaABF1 plays an important role in hormone-mediated regulation of seed dormancy and germination of cereal grains. Evidence shows that TaABF1 activity is regulated by phosphorylation, and previous work in our lab showed that when serine residues in its conserved regions; S36, S37, S113, S115 were altered to phosphomimetic aspartate, the 4xD TaABF1 mutant had increased activity as a transcription factor. However, when only S113 was altered, TaABF1’s activity was greatly reduced. The work presented here explored whether the S36D/S37D/S115D mutant would have stronger activity than the 4xD mutant. Using the particle bombardment technique to introduce the …
Haloferax Volcanii For Carotenoid Production, Erika Smith
Haloferax Volcanii For Carotenoid Production, Erika Smith
Honors Theses
Carotenoids are used as natural colorants and have been shown to have numerous health benefits, making these molecules highly desirable in the aquaculture, pharmaceutical, and nutraceutical markets. There is increasing consumer demand for the natural synthesis of carotenoids, but current methods are limited by the cost and difficulty of extraction from organisms. The halophilic archaeon Haloferax volcanii is amenable to extraction and has an endogenous carotenoid biosynthetic pathway that culminates in the accumulation of the carotenoid bacterioruberin; however, H. volcanii also synthesizes important precursors that can be converted into more highly-desired carotenoids, such as β-carotene and astaxanthin, in the presence …
Examining Interactions Between Opsins And Carotenoid Biosynthetic Proteins In Halophilic Archaea, Alexandru M. Plesa
Examining Interactions Between Opsins And Carotenoid Biosynthetic Proteins In Halophilic Archaea, Alexandru M. Plesa
Honors Theses
Organisms have evolved numerous specialized molecules for constantly responding to environmental changes. Examples of such molecules are the light-driven proton-pump rhodopsins, such as bacteriorhodopsin (BR) and cruxrhodopsin (cR), and the carotenoid pigments, such as retinal and bacterioruberin. In halophilic Archaea, retinal can covalently bind bacterioopsin (BO) and cruxopsin (CO) to form the corresponding protein complexes, and its biosynthesis is indirectly controlled by the activity of the lycopene elongase (Lye) enzyme, which converts lycopene, a retinal precursor, to a form of bacterioruberin. Interestingly, opsins were shown to inhibit the activity of Lye, thereby promoting retinal biosynthesis and indirectly regulating the apoprotein-cofactor …
Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks
Honors Theses
Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …
An Investigation Of Bag3 Knockdown And Its Effects On The Cytotoxicity Of Laromustine, Colin Sheehan
An Investigation Of Bag3 Knockdown And Its Effects On The Cytotoxicity Of Laromustine, Colin Sheehan
Honors Theses
Laromustine is a sulfonylhydrazine anticancer prodrug whose main cytotoxic arises from its ability to interfere with DNA replication of dividing cells. Multiple studies have suggested that Laromustine induces a form of cell death known as apoptosis. In a previous study investigating the mechanism of apoptosis, bcl2-associated athanogene 3 (BAG3) demonstrated significant upregulation in the presence of Laromustine. Given its anticancer ability, we selected BAG3 as a target for further investigation. BAG3 knockdown through transient shRNA transfections was performed in U138 glioblastoma multiforme cells and verified using qRT-PCR analysis. Finally, cell death assays were used to assess Laromustine’s cytotoxic effect on …
Optimization Of A Chemical Genetic Screen To Identify Druggable Targets In U138 Cells Treated With Laromustine, Kathryn Coe
Optimization Of A Chemical Genetic Screen To Identify Druggable Targets In U138 Cells Treated With Laromustine, Kathryn Coe
Honors Theses
Laromustine is an experimental sulfonylhydrazine prodrug used in late-stage clinical studies against acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). Despite initial promise for both indications, clinical trials for GBM have not been as successful as those for AML. To investigate methods for improving the effectiveness of laromustine in GBM and to learn more about the mechanism of action of laromustine, a chemical genetic screen will be conducted to identify agents that sensitize GBM cells to the anti-proliferative effects of laromustine. The library, which will include approximately 450 FDA-approved drugs, will be screened using a newly optimized high throughput assay …
Investigating The Effects Of Bag3 Knockdown On The Cytotoxicity Of The Anticancer Drug Laromustine, Kayla Gross
Investigating The Effects Of Bag3 Knockdown On The Cytotoxicity Of The Anticancer Drug Laromustine, Kayla Gross
Honors Theses
Laromustine is a sulfonylhydrazine anticancer prodrug whose cytotoxicity results from the formation of interstrand cross-links caused by the synergistic action of co- generated 2-chloroethylating and carbamoylating species. The cytotoxic activities of Laromustine involve the induction of apoptosis. Described herein is an investigation into this drug’s effects on apoptotic gene expression in HL-60 cells using qRT-PCR. Significant changes in the expression levels of 13 genes were observed, most dramatically in the upregulation of the bcl2-associated athanogene 3 (BAG3) gene. Given the pro-survival role of BAG3 in the cell, this investigation sought to decrease BAG3 mRNA levels in HL-60 cells using transient …
Relationship Of Cross-Linking Potential To Mechanism Of Cell Death, Adam N. Spierer
Relationship Of Cross-Linking Potential To Mechanism Of Cell Death, Adam N. Spierer
Honors Theses
Mechlorethamine (HN2), a nitrogen derivative of mustard gas, was the first synthetic anti-tumor chemotherapeutic because it forms covalent cross-links between strands of duplex DNA. HN2 represents a class of bifunctional alkylating agents that are both chemotherapeutic and carcinogenic: diepoxybutane (DEB), the active form of the pro-drug treosulfan, and epichlorohydrin (ECH), a structural hybrid of HN2 and DEB, also form covalent cross-links between DNA. While HN2 and DEB are clinically used as anti-tumor chemotherapeutics, ECH is a structural hybrid of these two compounds not used in a clinical setting. Accordingly, we aimed to understand the relationship between the cross-linking potential of …
The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff
The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff
Honors Theses
Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …
Patterns Of Apoptotic Poly(Adp-Ribose) Polymerase Cleavage Induced By Laromustine And Its Analogs, Adam N. Paine
Patterns Of Apoptotic Poly(Adp-Ribose) Polymerase Cleavage Induced By Laromustine And Its Analogs, Adam N. Paine
Honors Theses
The anticancer prodrug Laromustine (VNP40101M) has produced promising remission rates in clinical trials among leukemic patients relative to currently available chemotherapeutics. Such improvements demand that the agent’s mechanism of action be elucidated. This study aimed to determine the role of poly(ADP-ribose) polymerase (PARP) in Laromustine-induced cell death. Previous studies indicated that the methyl isocyanate produced upon activation of Laromustine is largely responsible for its effective induction of apoptosis. Results reported herein strongly support the activation of a PARP-dependent apoptotic pathway by Laromustine’s carbamoylating and chlorethylating subspecies. Furthermore, it is evident that the Laromustine-induced PARP-dependent apoptosis is primarily attributable to methyl …