Biochemistry Commons^™

The Role Of Diet In The Onset Of Depression: A Biochemical Connection Between Nutrition And Mental Health, Katlin Wildeman

Senior Honors Theses

Depression is a major clinical concern, having a complex onset and the presence of multiple, often unidentifiable causes. Depression affects millions of individuals worldwide, with a high prevalence in regions of the world with a Western-style diet as compared to regions with a Mediterranean diet. A Western-style diet consists of foods high in sugar, fat, and processed meats and grains, whereas the Mediterranean diet contains significantly more vegetables, fruits, lean meats, and whole grains. The link between diet and mental health disorders has implications for individuals of all ages who are hesitant to turn to medication. In addition to presenting …

Aminoacyl-Trna Synthetases, Miguel Angel Rubio Gomez, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The aminoacyl-tRNA synthetases are an essential and universally distributed family of enzymes that plays a critical role in protein synthesis, pairing tRNAs with their cognate amino acids for decoding mRNAs according to the genetic code. Synthetases help to ensure accurate translation of the genetic code by using both highly accurate cognate substrate recognition and stringent proofreading of noncognate products. While alterations in the quality control mechanisms of synthetases are generally detrimental to cellular viability, recent studies suggest that in some instances such changes facilitate adaption to stress conditions. Beyond their central role in translation, synthetases are also emerging as key …

The Classification Of An Unknown Protein 3h04, Britney Dyszel

Biochemistry and Molecular Biology Presentations

An unclassified protein in the Protein Data Bank, 3H04, was selected as a protein of interest. Research was performed in silico to gain key information on the structure, sequence, and homology of protein 3H04. This research was guided using the BASIL Project’s protocols on in silico research. Several databases were utilized to study protein 3H04. Based on the data gathered, unclassified protein 3H04 is an aminopeptidase that cleaves prolyl-dipeptidyl peptide bonds through alpha beta hydrolase function.

Probing The Function Of Perilipin 5b, Rebekah Dalton

Undergraduate Honors Thesis Projects

Many modern health issues arise from aberrant lipid metabolism, among these are type II diabetes and non-alcoholic fatty liver disease. One commonality these diseases share is neutral lipid metabolism and storage. Regulation of neutral lipid metabolism is of vital importance in the body, and among the proteins responsible for such regulation are the perilipins. Perilipins are a family of five conserved proteins that are found on the surface of lipid storage droplets and play a central role in the regulation of cellular neutral lipid metabolism. Perilipin 5 specifically, is expressed in tissues with a high capacity for fatty acid oxidation …

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of platinum-based …

Optimization Of Methods For Cross-Species Infection Of Cell Cultures With Wolbachia, Sarah J. Lane

Honors Thesis

The common intracellular endosymbiont genus of bacteria called Wolbachia is of interest due to the promise it shows for playing a role in disease control. Wolbachia have a number of widely variable effects on its many species of host insects. In combination with these roles, Wolbachia largely affects reproduction and development of its host species. It can lead to feminization and cytoplasmic incompatibility (Werren et al. 2008). Furthermore, this species is vertically transmitted which means that it passes from mother to offspring (Caragata et al., 2016). In combination with its effects on reproduction, which can allow Wolbachia to propagate through …

A Broadly Distributed, Novel Class Of Diiron Enzymes Involved In Para-Aminobenzoate Synthesis, Joseph M. Zambelas

Senior Theses

The overall structure and ligand arrangement of diiron enzymes influence their function and catalytic potential, allowing for them to catalyze an expansive breadth of high energy transformations. The diiron enzyme CADD from Chlamydia trachomatis is involved in a novel biosynthetic pathway for p-aminobenzoic acid (pABA), a precursor for tetrahydrofolate. The unique ligand structure and reactivity of CADD and homolog NE1434 provide an intriguing means to contrast structure function relationships with other known diiron enzymes that activate dioxygen. In this work, studies of CADD and NE1434 orthologs and comparison to other diiron enzymes reveal several sequence motifs that are likely critical …

Understanding How Human Lipoxygenases Bind Molecular Oxygen And Arachidonic Acid Substrate, Austin Paul Primeaux

Honors Capstones

No abstract provided.

Functions Of Cdk/Cyclin Complexes In Endoreplication Regulation By The Cdk Inhibitor Siamese, Kai Wang

LSU Doctoral Dissertations

Arabidopsis trichome (leaf hair) is a specialized single cell extended from epidermal cell on the leaves, which is a typical endoreplication and is also known as endoreduplication. Several D-type cyclins were tested to check the cell division in trichome, and the trichome expressing either CYCB1;2 or CDKB2;2 cannot trigger cell division, even if simultaneous expression of CYCB1;2 and CDKB2;2 failed to produce mitosis in trichome. Only CYCD3;1 specifically promotes multicellular trichome. cdkb1;1cdbk1;2 double mutants and sim cdkb1;1cdkb1;2 triple mutants exhibit the phenotype similar to the wild type and very limited cell division respectively. Overexpression of a CDKB1;1 dominant-negative construct that …

Characterization And Assembly Of The Pseudomonas Aeruginosa Aspartate Transcarbamoylase-Pseudo Dihydroorotase Complex, Chandni Patel, Asmita Vaishnav, Brian Fp Edwards, David R. Evans

Biochemistry and Molecular Biology Faculty Publications

Pseudomonas aeruginosa is a virulent pathogen that has become more threatening with the emergence of multidrug resistance. The aspartate transcarbamoylase (ATCase) of this organism is a dodecamer comprised of six 37 kDa catalytic chains and six 45 kDa chains homologous to dihydroorotase (pDHO). The pDHO chain is inactive but is necessary for ATCase activity. A stoichiometric mixture of the subunits associates into a dodecamer with full ATCase activity. Unlike other known ATCases, the P. aeruginosa catalytic chain does not spontaneously assemble into a trimer. Chemical-crosslinking and size-exclusion chro- matography showed that P. aeruginosa ATCase is monomeric which accounts for its …

A Halogen Bonding Perspective On Iodothyronine Deiodinase Activity, Eric S. Marsan, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Iodothyronine deiodinases (Dios) are involved in the regioselective removal of iodine from thyroid hormones (THs). Deiodination is essential to maintain TH homeostasis, and disruption can have detrimental effects. Halogen bonding (XB) to the selenium of the selenocysteine (Sec) residue in the Dio active site has been proposed to contribute to the mechanism for iodine removal. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known disruptors of various pathways of the endocrine system. Experimental evidence shows PBDEs and their hydroxylated metabolites (OH-BDEs) can inhibit Dio, while data regarding PCB inhibition are limited. These xenobiotics could inhibit Dio activity by competitively …

Targeting Trna-Synthetase Interactions Towards Novel Therapeutic Discovery Against Eukaryotic Pathogens, Paul Kelly, Fatemeh Hadi-Nezhad, Dennis Y. Liu, Travis J. Lawrence, Roger G. Linington, Michael Ibba, David H. Ardell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, …

Assessment Of Soil Protein And Refractory Soil Organic Matter Across Two Chronosequences Of Newly Developing Marshes In Coastal Louisiana, Usa, Stuart Alexander Mcclellan

LSU Doctoral Dissertations

The impacts of sea-level rise and hydrologic manipulation are threatening the stability of coastal marshes throughout the world, thereby increasing the potential for re-mineralization of soil organic matter (SOM) in these systems. Such threats have prompted marsh restoration efforts, particularly in coastal Louisiana, yet it is unclear how the slowly decomposing (refractory) and quickly decomposing (labile) fractions of SOM may be differentially affected by different approaches to marsh restoration. Additionally, otherwise labile compounds may accumulate in the soil via a range of protective mechanisms, including rapid burial and association with organic compounds that are thought to enhance soil aggregation, such …

Hur Ubiquitination By Brca1/Bard1 And Its Role In Controlling Gene Expression During Dna Damage Response, Gamage M. Aruggoda

Dissertations, Theses, and Capstone Projects

Despite our understanding of the biochemistry of the BRCA1/BARD1 E3 ligase, we know very little of the mechanism by which its cellular substrates, how they are chosen, how its E3 Ub ligase activity is regulated, which are the cofactors involved in this regulation, and how the substrates are modified during DDR. In this dissertation, I further evaluate BRCA1/BARD1-mediated E3 ligase activity and how CstF-50 and p97 regulate this reaction working as cofactors. My data show that BRCA1/BARD1 is an E3 ligase that ubiquitinates the RNA binding protein Human antigen R(HuR).

HuR is abundant in the nucleus and is transported to …

Synthesis And Preliminary Ex Vivo Testing Of Sirna Targeting Tcrb: A Proposed Therapy For The Treatment Of Autoimmunity, Nicholas J. Magazine

LSU Doctoral Dissertations

Abstract

Background:

As of 2018, the United States National Institutes of Health estimate that over half a billion people worldwide are affected by autoimmune disorders. Though these conditions are prevalent, treatment options remain relatively poor, relying primarily on various forms of immunosuppression which carry potentially severe side effects and often lose effectiveness overtime. Given this, new forms of therapy are needed. We propose small-interfering RNA (siRNA) for hypervariable regions of the T-cell receptor β-chain gene (TCRb) as a highly targeted, novel means of therapy for the treatment of autoimmune disorders.

Objectives:

To develop methods to produce siRNA targeting …

Sorting Of Cargo Proteins Within The Regulated Secretory Pathway: The Peripheral Membrane Protein Hid-1 As A Sorting And Vesicle Biogenesis Factor, Blake H. Hummer

Electronic Theses and Dissertations

Large dense core vesicles (LDCVs) form at the trans-Golgi network (TGN) and mediate the regulated release of neuropeptides and peptide hormones. Despite their central role to physiology, the mechanisms controlling biogenesis and sorting to LDCVs is not well understood. Optimizing the retention using selective hooks (RUSH) method in neuroendocrine cells, we show it is possible to visualize sorting to the constitutive and regulated secretory pathways in real-time and that the bulk of transmembrane LDCV cargoes do not sort directly onto LDCVs, but exit the TGN into non-regulated vesicles to be incorporated to LDCVs at a later step. Additionally, we characterize …

Use Of Alkoxyamines To Quantify And Map Uracils And To Kill B Cell Cancers, Madusha Lakshani Watuthanthrige Perera

Wayne State University Dissertations

Majority of B-cell lymphoma and leukemia originates in germinal centers and over express AID resulting high levels of uracils and eventually AP sites. Treating cells with a small alkoxyamine AA3 with a terminal alkyne group specifically killed B cell lymphoma cell lines without killing normal human B cells and non-hematological cancers. To study the cytotoxicity of AA3, I designed and synthesized a series of AA3 analogs with and without the alkyne group. Using cytotoxicity assays I demonstrated that the alkyne functionality plays a major role in AA3 cytotoxicity in B-cell cancers and further showed that the effectiveness is modulated by …

Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous

Wayne State University Dissertations

Colorectal cancer (CRC) constitutes a major burden on the healthcare system as the second most commonly diagnosed cancer in the developed world. Dietary folate is considered an important modulator of colorectal cancer. Folate restriction has been implicated in increasing CRC incidence by disrupting nucleotide synthesis, Impacting DNA methylation and inducing genetic instability. Our research shows that the timing and duration of dietary folate restriction can differentially impact Colorectal cancer initiation. Acclimating mice to folate restriction for 8 weeks results in a reduced number of preneoplastic lesions compared to mice placed of folate restriction for 1 week prior to initiating the …

Effect Of Mptp On Α-Synuclein Spreading, Accumulation And Toxicity In Mice With Intrastriatal Innoculation Of Human Α-Synuclein Preformed Fibril, Madiha Mohieldin Merghani

Theses

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, characterized by abnormal accumulation of interneuronal inclusions of α-synuclein (α-syn) known as Lewy bodies (LBs) and Lewy neurites (LNs), and significant loss of dopamine neurons in the substantia nigra pars compacta (SNc) region of the brain. Recent evidence suggests that intrastriatal inoculation of α-syn Preformed Fibril (PFF) into mice induces PD-like LBs and LNs pathology formed by aggregated α-syn in anatomically interconnected brain regions which needs several months of incubation to develop the pathology. In the present study, we have evaluated the effect of different doses of 1-methyl, 4-phenyl, …

Characterization Of The Influences Of Human Cytomegalovirus Glycoprotein O (Go) Expression On Gh/Gl Complexes Assembly And Its Polymorphisms On Cell-Free And Cell-To-Cell Spread, And Antibody Neutralization., Le Z. Day

Graduate Student Theses, Dissertations, & Professional Papers

Human cytomegalovirus (HCMV) is widely spread throughout the world and immunocompromised individuals can suffer severe diseases from HCMV infection. Once the infection is established, HCMV can spread through the body and infect many major somatic cell types. The glycoproteins H and L (gH/gL) on HCMV envelope can be bound by either gO or the UL128-131 proteins to form complexes gH/gL/gO and gH/gL/UL128-131 that are critical for viral entry and spread, and these two complexes are important targets of neutralizing antibodies. Strains of HCMV vary considerably in the levels of gH/gL/gO and gH/gL/UL128-131. gO is one of the most diverse loci …

Anti-Tumor Functions Of Sphingosine Kinase 1 And Sphingosine Kinase 2 In Breast Cancer Development, Melissa A. Maczis

Theses and Dissertations

Bioactive sphingolipid metabolite sphingosine-1‐phosphate (S1P) circulating levels have been implicated in breast cancer (BC) progression. BCs usually respond to 17β-Estradiol (E2) through canonical receptor ERα66 for genomic effects, however, E2 also triggers rapid, non-genomic responses. E2 has been shown to activate sphingosine kinase 1 (SphK1), increasing S1P for S1P receptors signaling important for BC. The E2 receptor activating SphK1 has not been identified. We demonstrate triple negative BC cells, expressing only novel ERα splice variant ERα36, E2-induced SphK1 activation for S1P secretion. Tamoxifen, first-line BC endocrine therapy, an ERα66 antagonist but ERα36 agonist, activates SphK1 and increases S1P secretion in …

“C1orf150”: A Novel Regulator Of Jak2 Kinase, And Candidate Tumor Suppressor In Human Blood Cell Progenitors, Tyler M. Wade

Honors Theses and Capstones

Erythropoietin (EPO) is an essential growth factor for red blood cell (RBC) production. In response to anemia, hypoxia-sensing cells in the kidney express and release EPO. EPO then acts in bone marrow to drive RBC formation from erythroid progenitors. Upon binding to its cell surface receptor, EPO triggers a JAK2 kinase signaling cascade for progenitor cell growth. Our lab has discovered a novel regulator of JAK2, “C1ORF150” (“150”). “150” is conserved in H sapiens and primates and is a new orthologue of the B-cell receptor adaptor protein and tumor marker, HGAL. Using a shRNA knockdown approach, I investigated the actions …

Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau

Legacy Theses & Dissertations (2009 - 2024)

Diabetes is a global health epidemic that can be devastating to those afflicted,

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance …

Application Of Β-Chloroenals: One-Pot Syntheses To Create Highly Variable, Functional, And Biologically Interesting Molecules, Julia Powell Siewert

Honors Theses

Pyrroles and pyrazoles are privileged structures which provide a molecular framework found in many different classes of bioactive compounds, thus rendering their syntheses useful in pharmaceutical drug development. Additionally, being able to selectively create these molecules with interesting substituents allows for different pharmacological and biological activities, such as antitumor and antibiotic effects. Our group has used β-chloroenals in the application of many different unique synthetic strategies in the past, and here I show that chloroenals can be used to synthesize novel 1,2,5 trisubstituted pyrroles as well as 1,5 di- and 1,4,5 trisubstituted pyrazoles in fewer steps and with milder conditions …

The Effects Of Signaling Molecules To Agrobacterium Tumefaciens Tumorigenesis At Plant Wound Sites, Nicole Walker

Honors Theses

Agrobacterium tumefaciens can live independently within soil before infecting its host (McCullen and Binns, 2006). The bacterium infects the plant through the rhizosphere, an area of soil along the plant root surface which contains microorganisms, making up the “external metabolome” (Bais et al. 2006). As these bacteria live in the rhizosphere, they are exposed to a multitude of chemical signals. These chemical signals include several conditions that must be met before the virulence machinery is expressed. These conditions include signaling from phenols and sugars as well as low PO4 levels and low pH. Upon wounding, sugars and phenols are released …

Antibiotic Drug Nanocarriers For Probing Of Multidrug Abc Membrane Transporter Of Bacillus Subtilis, Pavan Kumar Cherukuri, Preeyaporn Songkiatisak, Feng Ding, Jeam-Michel Jault, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters can extrude a wide range of substrates, which cause multidrug resistance and ineffective treatment of diseases. In this study, we used three different sized antibiotic drug nanocarriers to study their size-dependent inhibitory effects against Bacillus subtilis. We functionalized 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm silver nanoparticles (Ag NPs) with a monolayer of 11-amino-1-undecanethiol and covalently linked them with antibiotics (ofloxacin, Oflx). The labeling ratios of antibiotics with NPs are 8.6 × 10², 9.4 × 10³, and 6.5 × 10⁵ Oflx molecules per NP, respectively. We designed …

Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia

Wayne State University Dissertations

Rat1 is a 5′→3′ exoribonuclease in budding yeast belonging to the XRN-family of nucleases. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its homolog in metazoan have been shown to function in multiple facets of RNA metabolism. In this study, we report a novel role of Rat1 in splicing of pre-mRNA in budding yeast. In the absence of the functional Rat1 in the nucleus, an increase in the level of unspliced transcripts was observed in yeast cells. Strand-specific TRO analysis revealed that the accumulation of unspliced transcripts upon …