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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Neuro And Hepatic Toxicological Profile Of (S)-2,4-Diaminobutanoic Acid In Embryonic, Adolescent And Adult Zebrafish, Rosa-Maria Ferraiuolo, Daniel Meister, Dominique Leckie, Jonathan Franke, Lisa A. Porter, John F. Trant Aug 2019

Neuro And Hepatic Toxicological Profile Of (S)-2,4-Diaminobutanoic Acid In Embryonic, Adolescent And Adult Zebrafish, Rosa-Maria Ferraiuolo, Daniel Meister, Dominique Leckie, Jonathan Franke, Lisa A. Porter, John F. Trant

Chemistry and Biochemistry Publications

(S)-2,4-Diaminobutanoic acid (DABA) is a noncanonical amino acid often co-produced by cyanobacteria along with β-N-methylamino-l-alanine (BMAA) in algal blooms. Although BMAA is a well-established neurotoxin, the toxicity of DABA remains unclear. As part of our development of biocompatible materials, we wish to make use of DABA as both a building block and as the end-product of enzymatically-induced depolymerization; however, if it is toxic at very low concentrations, this would not be possible. We examined the toxicity of DABA using both in vivo embryonic and adult zebrafish models. At higher sub-lethal concentrations (700 µM), the fish demonstrated early …


An Assessment Of Bsa Protein Hydrogel Biocompatibility In The Vertebrate Intestinal Tract, Ryan Joseph Garde Aug 2019

An Assessment Of Bsa Protein Hydrogel Biocompatibility In The Vertebrate Intestinal Tract, Ryan Joseph Garde

Theses and Dissertations

The fields of biomedicine and pharmacology have a mission to design methods to treat disease while minimizing adverse side effects using novel drug delivery systems. In developing new therapeutic systems, it is crucial to test that drug delivery systems target pathological cells and tissue and is non-toxic in healthy tissue. One promising method for targeted drug delivery is the use of hydrogels as carriers. Here, we studied the effects of bovine serum albumin (BSA) hydrogel consumption to assess the potential for hydrogel use in treating intestinal disease via oral administration. We investigated intestinal architecture and cell populations following hydrogel treatments …


Examining Lateral Line Development Through Cxcl14 Modulation Of Cxcl12-Cxcr4 Mediated Gene Expression In Danio Rerio, Ariana Calderon-Zavala May 2019

Examining Lateral Line Development Through Cxcl14 Modulation Of Cxcl12-Cxcr4 Mediated Gene Expression In Danio Rerio, Ariana Calderon-Zavala

Lawrence University Honors Projects

The lateral line is a mechanosensory system used by fish to sense the movement of water. It is evolutionarily related to the inner-ear in humans. For both organisms, the binding of the CXCL12 (SDF-1 ligand) to the CXCR4 receptor induces conformational changes needed to activate signal transduction. This signaling results in numerous cellular responses such as cell fate, chemotaxis, and gene transcription. Interestingly, researchers have found that another signaling molecule, CXCL14, can also bind to the CXCR4 receptor with high affinity (Tanegashima et al., 2013). As a result, we hypothesize that CXCL14 modulates CXCL12-mediated chemotaxis, presumably acting as an allosteric …


Semisynthetic Aurones Inhibit Tubulin Polymerization At The Colchicine-Binding Site And Repress Pc-3 Tumor Xenografts In Nude Mice And Myc-Induced T-All In Zebrafish, Yanqi Xie, Liliia M. Kril, Tianxin Yu, Wen Zhang, Mykhaylo S. Frasinyuk, Svitlana P. Bondarenko, Kostyantyn M. Kondratyuk, Elizabeth Hausman, Zachary M. Martin, Przemyslaw P. Wyrebek, Xifu Liu, Agripina G. Deaciuc, Linda P. Dwoskin, Jing Chen, Haining Zhu, Chang-Guo Zhan, Vitaliy M. Sviripa, Jessica S. Blackburn, David S. Watt, Chunming Liu Apr 2019

Semisynthetic Aurones Inhibit Tubulin Polymerization At The Colchicine-Binding Site And Repress Pc-3 Tumor Xenografts In Nude Mice And Myc-Induced T-All In Zebrafish, Yanqi Xie, Liliia M. Kril, Tianxin Yu, Wen Zhang, Mykhaylo S. Frasinyuk, Svitlana P. Bondarenko, Kostyantyn M. Kondratyuk, Elizabeth Hausman, Zachary M. Martin, Przemyslaw P. Wyrebek, Xifu Liu, Agripina G. Deaciuc, Linda P. Dwoskin, Jing Chen, Haining Zhu, Chang-Guo Zhan, Vitaliy M. Sviripa, Jessica S. Blackburn, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using …


Determining The Key Residues For Capsule Production In The Gbs Cpsa Protein, Anna Struba Apr 2019

Determining The Key Residues For Capsule Production In The Gbs Cpsa Protein, Anna Struba

Honors College

Streptococcus agalactiae (GBS) is a common bacterium found commensally in the vaginal mucosa of healthy adults. GBS also causes severe infection in neonates, often leading to meningitis, which can cause lifelong health consequences including impaired hearing and seizures. Infection of newborns mainly arises from a colonized mother, either before birth through ascending infection or during labor. Ascending infection, where the bacteria travel to the fetus from the vaginal mucosa, is especially concerning as it can lead to loss of pregnancy or premature birth. The most common method of neonatal GBS disease prevention is antibiotic prophylaxis during delivery, though this method …


Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System, Yiran Tao Jan 2019

Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System, Yiran Tao

Honors Program Theses

The motility of mitochondria is required for providing energy and maintaining basic cellular functions in neurons. Mitochondrial Rho GTPase (Miro) is an essential component of the mitochondrial trafficking machinery, a protein complex that anchors mitochondria to the microtubule motor protein for long-distance transport. As a protein localizing to the mitochondrial outer membrane, Miro regulates the morphology and the motility of mitochondria. Upon mitochondrial depolarization, the PINK1/Parkin pathway is activated to arrest mitochondrial movement by targeting Miro for phosphorylation and ubiquitination in a calcium-sensitive manner. However, it remains unclear what effects the PINK1-dependent phosphorylation has on the structure and binding properties …