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Full-Text Articles in Life Sciences

Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis Nov 2014

Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis

Doctoral Dissertations

Protein transduction domains (PTDs) and their and their synthetic mimics are short sequences capable of unusually high uptake in cells. Several varieties of these molecules, including the arginine-rich Tat peptide from HIV, have been extensively used as vectors for protein, DNA, and siRNA delivery into cells. Despite the wide-ranging utility of PTDs and their mimics, their uptake mechanism is still under considerable debate. How the molecules are able to cross phospholipid membranes, and what structural components are necessary for optimal activity are poorly understood. This thesis explores how PTDMs interact with phospholipid membrane phase, anionic lipid content and negative Gaussian ...


Nanoparticle Building Blocks For Functional Structures, Youngdo Jeong Nov 2014

Nanoparticle Building Blocks For Functional Structures, Youngdo Jeong

Doctoral Dissertations

A major goal in material science is achieving a desired function using structures fabricated with designed building blocks. Advanced synthetic and self-assembly techniques allow various nanomaterials to become promising building blocks, providing the control of the interaction between building blocks. The unique properties of nanomaterials can be transferred to structured systems. Among nanomaterials, inorganic nanoparticles such as gold nanoparticles (AuNPs), magnetic particles, and quantum dots (QDs) provide useful physical properties stemming from their inorganic core, large surface areas, and oriented surface functionalities. My research has focused on fabricating functional systems using gold nanoparticles (AuNPs), manipulating the interaction between AuNPs, bio-entities ...


Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii Nov 2014

Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii

Doctoral Dissertations

Factor Inhibiting HIF (FIH) is a Fe(II)-αKG dependent oxygenase that acts as a cellular oxygen sensor in humans. FIH regulates the transcriptional activity of the hypoxia-inducible factor-1 (HIF-1a or HIF), a transcription factor responsible cellular O2 homeostasis. Hydroxylation of the target residue HIF-Asn803, found in the C-terminal transactivation domain (CTAD), inactivates HIF-dependent gene expression. Central to FIH’s function is the activation of O2 after CTAD binding. The mechanistic and structural features of FIH leading to tight coupling between CTAD binding and subsequent O2-activation and reactivity are key for efficient O2 sensing ...


The Estradiol-Induced Transcriptome Of The Female Mouse Anteroventral Periventricular Nucleus: More Than Just A Kiss, Leah K. Aggison Nov 2014

The Estradiol-Induced Transcriptome Of The Female Mouse Anteroventral Periventricular Nucleus: More Than Just A Kiss, Leah K. Aggison

Doctoral Dissertations

Estradiol (E2) is critical in the reproductive mechanisms of mammals. In female rodents E2 acts through the neurons of the anteroventral periventricular nucleus (AVPV) to exert neuroendocrine control over ovulation, via synaptic activation of the gonadotropin releasing hormone (GnRH) neurons. The neurocircuitry of the AVPV is complex, receiving input from the suprachiasmatic nucleus and ventral premammillary nucleus and the as well as projecting to organum vasculosum of lamina terminalis and the arcuate. This suggests a broader role for the AVPV as a center of multisignal-integration in regards to ovulation. I used full genome expression microarrays to assess the ...


Properties Of Potential Substrates Of A Cyanobacterial Small Heat Shock Protein, Yichen Zhang Nov 2014

Properties Of Potential Substrates Of A Cyanobacterial Small Heat Shock Protein, Yichen Zhang

Masters Theses

Most proteins must fold into native three-dimensional structures to be functional. But, newly synthesized proteins are at high risk of misfolding and aggregating in the cell. Stress, disease or mutations can also cause protein aggregation. A cyanobacterial small heat shock protein, Hsp16.6, can act as a chaperone to prevent irreversible protein aggregation during heat stress. This thesis is focused on the properties of proteins that were associated with Hsp16.6 during heat stress, and which therefore may be “substrates” of Hsp16.6. Bioinformatics were used to determine if Hsp16.6 preferentially binds to proteins with certain properties, and biochemical ...


Expression And Purification Of Human Lysosomal Β-Galactosidase From Pichia Pastoris, Sarah E. Tarullo Nov 2014

Expression And Purification Of Human Lysosomal Β-Galactosidase From Pichia Pastoris, Sarah E. Tarullo

Masters Theses

Lysosomal storage diseases are genetically inherited diseases caused by the dysfunction of lysosomal enzymes. In a normal cell, lysosomal enzymes cleave specific macromolecules as they are transported to the lysosome. However, in diseased cells, these lysosomal enzymes are either absent or malfunctioning, causing macromolecular substrates to accumulate, becoming toxic to the cell. Over fifty lysosomal storage diseases have been identified, collectively occurring in one out of 7,700 live births. We investigated the lysosomal enzyme β-galactosidase (β-gal). In order to study the biochemistry and enzymology of this protein a robust expression system was needed. The GLB1 gene has been inserted ...


Sequence Analysis Of Maize Yellow Stripe3 Candidate Genes, Dennis B. Depaolo Nov 2014

Sequence Analysis Of Maize Yellow Stripe3 Candidate Genes, Dennis B. Depaolo

Masters Theses

The work presented here focuses on the molecular mechanism of phytosiderophore secretion in graminaceous plants. In maize, yellow stripe3 (ys3) is a mutant that is deficient in its ability to secrete iron-chelating compounds of the mugineic acid family known as phytosiderophores. Phytosiderophores are specific to grasses and are used for the acquisition of iron. Genetic linkage mapping of the ys3 locus lead to a region of interest on chromosome 3 defined by marker UMC1773. The sequence of eleven candidate genes (GRMZM2G390345, GRMZM2G390374, GRMZM2G342821, GRMZM5G800764, GRMZM2G502560, GRMZM5G849435, GRMZM2G105766, GRMZM5G876835, GRMZM2G036976, GRMZM2G502563, miR167g) revealed several small deletions and point mutations within the ...


Designing A Pore-Forming Toxin Cytolysin A (Clya) Specific To Target Cancer Cells, Alzira Rocheteau Avelino Nov 2014

Designing A Pore-Forming Toxin Cytolysin A (Clya) Specific To Target Cancer Cells, Alzira Rocheteau Avelino

Masters Theses

Cytolysin A (ClyA) is a member of a class of proteins called pore-forming toxins (PFTs). ClyA is secreted by Gram-negative bacteria, and it attacks a number of mammalian cells by inserting into and forming channels within the cell membrane (Oscarsson J et al., 1999). It has been suggested that ClyA binds to cholesterol (Oscarsson J et al., 1999) and thus can insert into the membranes of many different cell types of eukaryotic origin. In our studies we propose to engineer a ClyA protein that can only attack a small subset of cell types. We propose to engineer ClyA that can ...


Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky Aug 2014

Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky

Doctoral Dissertations

Glycosaminoglycans (GAGs), highly charged biological polyelectrolytes, are of growing importance as biomaterials and pharmaceutical drugs due to their immense range of physiological functions. They bind to many proteins; however, the degree of structural selectivity in GAG-protein interactions is largely unknown .Our studies have focused on the importance of heparin (a model GAG) charge and chain length in protein binding in order to explore its potential applications in biofunctional tissue scaffold materials, as polysaccharide drugs in anticoagulation, and as inhibitory agents in protein aggregation. We used electrospray ionization mass spectrometry, capillary electrophoresis, size exclusion chromatography, dynamic/static light scattering and electrostatic ...


Novel Strategies To Modulate Synaptic Communication And Investigate The Role Of Hdac6 In Alzheimer’S Disease, Kathryne A. Medeiros Aug 2014

Novel Strategies To Modulate Synaptic Communication And Investigate The Role Of Hdac6 In Alzheimer’S Disease, Kathryne A. Medeiros

Doctoral Dissertations

Neuronal communication is mediated by chemical signaling at the synapse. The underlying molecular mechanisms of learning and memory are poorly understood. Very few tools are available to study how memories are formed in the mammalian brain. This dissertation focuses on developing novel strategies to study neural activity. Here we develop and use a chemical-genetic approach to enable target-specific photocontrol of inhibitory synaptic neurotransmission of GABAA receptor subtypes. The tools developed here selectively photocontrolled GABAA receptor subtypes. This enabled the investigation of the functional role these receptor subtypes have in inhibitory synaptic neurotransmission. This dissertation also focuses on identifying ...


Structural Biology And Pharmacology Of Human Cathepsin A And Neuraminidase 1, Nilima Kolli Aug 2014

Structural Biology And Pharmacology Of Human Cathepsin A And Neuraminidase 1, Nilima Kolli

Doctoral Dissertations

Human cathepsin A (also known as Protective Protein/Cathepsin A, PPCA; E.C. 3.4.16.5) is a lysosomal serine carboxypeptidase. Cathepsin A is also involved in a complex with two other lysosomal enzymes: lysosomal neuraminidase (NEU1, E.C. 3.2.1.18) and β-galactosidase (GLB1, E.C. 3.2.1.23). Deficiency in cathepsin A and NEU1 result in the lysosomal storage diseases, galactosialidosis and sialidosis respectively. Deficiency in GLB1 results in GM1 gangliosidosis and Morquio B diseases.

Cathepsin A protease activity is spatially regulated by activation of the inactive precursor form to the mature form in ...


Engineering Probes To Detect Cholesterol Accessibility On Membranes Using Perfringolysin O, Benjamin B. Johnson Aug 2014

Engineering Probes To Detect Cholesterol Accessibility On Membranes Using Perfringolysin O, Benjamin B. Johnson

Doctoral Dissertations

Cholesterol is an essential component of mammalian cell membranes and it is important to regulate the structure and function of lipid bilayers. Changes in cholesterol levels are involved in many physiological and pathological events such as the formation of arterial plaques, viral entry into cells, sperm capacitation, and receptor organization. Determination of cholesterol trafficking and distribution is essential for understanding how cells regulate cholesterol.

A key factor in the regulation of cholesterol is cholesterol accessibility. Through it interactions in the membrane, cholesterol is sequestered below the surface of the membrane. Based on the composition of the membrane, a certain amount ...


Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres Aug 2014

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of ...


Biophysical Studies Of Axonal Transport, Leslie Cyle Conway Apr 2014

Biophysical Studies Of Axonal Transport, Leslie Cyle Conway

Doctoral Dissertations

Intracellular transport provides a mechanism by which cellular material, such as organelles, vesicles, and protein, can be actively transported throughout the cell. This process relies on the activity of the cytoskeletal filament, microtubules, and their associated motor proteins. These motors are able to walk along microtubule tracks while carrying cellular cargos to enable the fast, regulated transport of these cargos. In cells, these microtubule filaments act as a binding platform for numerous different motor species as well as microtubule-associated proteins (MAPs). In addition, these filaments often form higher order structures, such as microtubule bundles. How motors navigate such complex, crowded ...


Honesty And Carotenoids In A Pigmented Female Fish, Alexandria Christine Brown Apr 2014

Honesty And Carotenoids In A Pigmented Female Fish, Alexandria Christine Brown

Doctoral Dissertations

The carotenoid tradeoff hypothesis states that diet-derived carotenoids are tradedoff among competing physiological demands, but this statement is rarely tested in ornamented females. The following dissertation tests the carotenoid tradeoff hypothesis in reverse sexually dimorphic convict cichlids (Amantitlania siquia) using carotenoidsupplemented diet treatments and a field-based study of carotenoid intake. Spectral, microscopic, and chemical analysis determined how females allocated the pigments to tissues and how those decisions affected their ventral patch coloration. The results presented in the current study show that carotenoids enhance offspring growth and survival, lower oxidative stress, and reduce the time to clear a parasite. The two ...


Reactive Probes For Manipulating Polyketide Synthases, And Photoreactive Probes For Strained Alkyne Click Chemistry, Jon William Amoroso Apr 2014

Reactive Probes For Manipulating Polyketide Synthases, And Photoreactive Probes For Strained Alkyne Click Chemistry, Jon William Amoroso

Doctoral Dissertations

Polyketides are a broad class of natural products that have received attention from the scientific community because they are a rich mine of bioactive structures. The common thread that binds the class together is the method by which they are synthesized, by large enzymatic complexes called polyketide synthases (PKSs) which display assembly line like organization. A great deal of effort has been put into studying PKSs, but their mechanistic steps are still not perfectly understood. In order to further the study of PKSs and their components, we have developed a series of reactive small molecules that covalently modify specific sites ...


Allosteric Regulation Of Dengue Virus Type 2 Protease, Muslum Yildiz Apr 2014

Allosteric Regulation Of Dengue Virus Type 2 Protease, Muslum Yildiz

Doctoral Dissertations

Dengue Fever is a global problem with a worldwide effectiveness that put 2.5 Billion people under the risk, infect 50 million people and causes 30000-50000 people death each year. DHF was first recognized in the 1950s during the dengue epidemics in the Philippines and Thailand. By 1970 nine countries had experienced epidemic DHF and now, the number has increased more than fourfold and continues to rise. Today emerging DHF cases are causing increased dengue epidemics in the Americas, and in Asia, where all four dengue viruses are endemic. Vaccine development against Dengue Virus has been impossible to date, due ...