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Synthesis And Evaluation Of Bodipy-, Azabodipy- And Chlorin-Based Conjugates For Imaging And Photodynamic Therapy Of Egfr-Overexpressing Cancers, Simran Dhingra

LSU Doctoral Dissertations

This dissertation discusses the design of EGFR-targeted small-molecule agents that unite molecular imaging with photodynamic therapy. Chapter 1 frames the clinical need for early detection and selective treatment and surveys BODIPY, aza-BODIPY, and chlorin scaffolds as tunable chromophores for near-infrared imaging and photosensitization. It also outlines EGFR as a validated target and compares two ligand classes used throughout this work: the tyrosine kinase inhibitor erlotinib and the cyclic peptide KLARLLT.

Chapter 2 describes the synthesis of a near-IR BODIPY bearing either one or two erlotinib units. Docking and SPR show specific interactions with the EGFR kinase domain, and both conjugates …

Infrared Laser Ablation Of Biomolecules From Formalin-Fixed Tissue, Blessing Chisom Egbejiogu

LSU Doctoral Dissertations

In the research described in this dissertation, a high-precision infrared laser ablation microsampling method was utilized for spatially resolved proteomic and lipidomic analyses of formalin fixed paraffin embedded (FFPE) tissue, a widely used archival sample in biomedical research. Despite its extensive use, FFPE tissue presents challenges for proteomic analysis due to protein cross-linking and modifications introduced during fixation, which can hinder extraction and identification. Developing a streamlined high-resolution method to recover biomolecules from FFPE samples is critical for advancing biomarker discovery, retrospective studies, and multi-omics research. To address these challenges, this study employs an infrared (IR) laser ablation microdissection system …

Early Preclinical Studies Of Ergosterol Peroxide And Biological Evaluation Of Its Derivatives, Taotao Ling, Luz V. Arroyo-Cruz, William R. Smither, Emily K. Seighman, Michelle M. Martínez-Montemayor, Fatima Rivas

Faculty Publications

Ganoderma lucidum is a medicinal mushroom that produces various pharmacological compounds, including triterpenoids. A major bioactive component of G. lucidum is ergosterol peroxide (EP), which is attributed to its anticancer effects. The current study focuses on the in vitro ADME (absorption, distribution, metabolism, and elimination), in vivo efficacy and toxicity of EP, and the synthesis of new EP derivatives to improve aqueous solubility. It was found that EP is metabolically stable in liver microsomes and plasma. In vivo studies showed that EP inhibits tumor growth in murine cancer models, and it is well tolerated by mice. The maximum tolerated dose …

International Consensus On Fasting Terminology, Daniela A. Koppold, Carolin Breinlinger, Etienne Hanslian, Christian Kessler, Holger Cramer, Anika Rajput Khokhar, Courtney M. Peterson, Grant Tinsley, Claudio Vernieri, Richard J. Bloomer, Michael Boschmann, Nicola L. Bragazzi, Sebastian Brandhorst, Kelsey Gabel, Alan C. Goldhamer, Martin M. Grajower, Michelle Harvie, Leonie Heilbronn, Benjamin D. Horne, Spyridon N. Karras, Jost Langhorst, Eva Lischka, Frank Madeo, Sarah J. Mitchell, Ioannis Eleemon Papagiannopoulos-Vatopaidinos, Maria Papagiannopoulou, Hanno Pijl, Eric Ravussin, Martha Ritzmann-Widderich, Krista Varady, Lilian Adamidou, Melika Chihaoui, Rafael De Cabo, Mohamed Hassanein

Clinical Research Faculty Publications

Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys. Consensus was achieved for the following terms: “fasting” (voluntary abstinence from some or all foods or foods and beverages), “modified fasting” (restriction of energy intake to max. 25% of energy needs), “fluid-only fasting,” “alternate-day fasting,” “short-term fasting” (lasting 2–3 days), “prolonged fasting” (≥4 consecutive days), and …

Boron Neutron Capture Therapy Of Cancer: Where Do We Stand Now?, Rolf F. Barth, Gong Wu, Maria Da Graca H. Vicente, John C. Grecula, Nilendu Gupta

Faculty Publications

No abstract provided.

Advances In Stereoselective Glycosylation: Electron-Withdrawing Groups, Benzyne-Mediated Stereoinversion, And Visible-Light Photochemistry For 1,2-Cis O-Glycosylation, Erik Giovanni Alvarez Valenzuela

LSU Doctoral Dissertations

The symbiotic relationship between humans and their microbiota is essential for health, with imbalances in the complex microbiota ecosystem linked to a variety of disorders ranging from neurodegenerative to gastrointestinal diseases. Bacteria within the human microbiota, comprising over 1000 known species, are densely and diversely coated with oligosaccharides crucial for functions like cell recognition, communication, signaling, adhesion, proliferation, and pathogenic inhibition. However, studying the structure-activity relationships of these sugars which are also secreted by bacteria is challenging due to difficulties in obtaining homogenous samples from natural sources.

Chemical synthesis offers a solution by enabling the production of well-defined oligosaccharides in …

Molecular-Level Studies Of Nanopatterned Biomolecules With Atomic Force Microscopy, Ashley R. Walker

LSU Doctoral Dissertations

Atomic force microscopy (AFM) is an analytical technique in which a tipped probe is gently scanned across the surface in a raster pattern to generate digital images of a sample at the nanoscale. The AFM instrument has three general operational modes, which are contact, non-contact and tapping-mode, that can be used to examine materials at the atomic level. Single-molecular details of biological molecules and other soft organic materials can be captured with minimal denaturation in either ambient or liquid environments when using tapping-mode AFM. In tapping-mode, the probe is driven to oscillate vertically while the tip is scanned across the …

Teaching Difficult Topics: Reflections From The Undergraduate Music Classroom, Olivia R. Lucas, Laura Moore Pruett

Faculty Publications

Teaching Difficult Topics provides a series of on-the-ground reflections from college music instructors working in a wide variety of institutional settings about their approaches to inclusive, supportive pedagogy in the music classroom. Although some imagine the music classroom to be an apolitical space, instructors find themselves increasingly in need of resources for incorporating issues of race and ethnicity, gender and sexuality, and historical trauma into their classrooms in ways that support student learning and safeguard their classroom communities. The teaching reflections in Teaching Difficult Topics examine difficult themes that fall into three primary categories: subjects that instructors sense to be …

Recent Advances In Chemistry And Antioxidant/Anticancer Biology Of Monoterpene And Meroterpenoid Natural Product, Benedict J. Barras, Taotao Ling, Fatima Rivas

Faculty Publications

Monoterpenes and meroterpenes are two large classes of isoprene-based molecules produced by terrestrial plants and unicellular organisms as diverse secondary metabolites. The global rising incidence of cancer has led to a renewed interest in natural products. These monoterpenes and meroterpenes represent a novel source of molecular scaffolds that can serve as medicinal chemistry platforms for the development of potential preclinical leads. Furthermore, some of these natural products are either abundant, or their synthetic strategies are scalable as it will be indicated here, facilitating their derivatization to expand their scope in drug discovery. This review is a collection of representative updates …

Synthesis Of An Acinetobacter Baumannii Lipooligosaccharide Subunit, James M. Armstrong Ii

LSU Doctoral Dissertations

Acinetobacter baumannii is a Gram-negative, multi drug-resistant bacterium that was placed on the World Health Organization’s watchlist of drug-resistant bacteria. A. baumannii is an ESKAPE pathogen, one of six increasingly antimicrobial-resistant bacteria that are responsible for nosocomial infections. Alternative therapies, such as vaccines, are required to decrease the world’s reliance on antimicrobial agents. Specifically, glycoconjugate vaccines such as those used against Haemophilus influenzae B, Streptococcus pneumoniae, and Neisseria meningitidis are used globally and are highly effective. These vaccines consist of an antigenic bacterial glycan bound to a carrier protein. The glycan is usually a capsular polysaccharide (CPS), however, the notion …

Synthesis And Characterization Of Porphyrin-Encapsulated Nanoparticles: Investigations With Scanning Probe Microscopy, Olajumoke Helen Olubowale

LSU Doctoral Dissertations

Scanning probe microscopy (SPM) encompasses a family of surface measurements that use a sharp probe to “feel” a surface. The tip is scanned point-by-point to build a map of the sample topography, which can be correlated with local measurements of surface properties. This dissertation outlines the history of SPM and describes techniques, operational modes, and applications. A review of force volume mapping (FVM), a 3D characterization mode of SPM used to map material properties detailed. Force volume mapping can be achieved by measuring multiple force measurements point-by-point in a grid pattern. Local properties such as chemical forces, dielectric properties, nanomechanical …

Discovery Of Novel Bioactive Tanshinones And Carnosol Analogues Against Breast Cancer, Miguel A. González-Cardenete, Natalia González-Zapata, Lucinda Boyd, Fatima Rivas

Faculty Publications

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 …

Expression Of The Preadipocyte Marker Zfp423 Is Dysregulated Between Well-Differentiated And Dedifferentiated Liposarcoma, Thanh N. Dang, Rafael P. Tiongco, Loren M. Brown, Jessica L. Taylor, John M. Lyons, Frank H. Lau, Z. Elizabeth Floyd

Division of Basic Science Faculty Publications

Background: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog …

Dynamic Modeling Of Aba-Dependent Expression Of The Arabidopsis Rd29a Gene, Ruth Ndathe, Renee Dale, Naohiro Kato

Faculty Publications

The abscisic acid (ABA) signaling pathway is the key defense mechanism against drought stress in plants. In the pathway, signal transduction among four core proteins, pyrabactin resistance (PYR), protein phosphatase 2C (PP2C), sucrose-non-fermenting-1-related protein kinase 2 (SnRK2), and ABRE binding factor (ABF) leads to altered gene expression kinetics that is driven by an ABA-responsive element (ABRE). A most recent and comprehensive study provided data suggesting that ABA alters the expression kinetics in over 6,500 genes through the ABF-ABRE associations in Arabidopsis. Of these genes, termed ABA gene regulatory network (GRN), over 50% contain a single ABRE within 4 kb of …

Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun

Faculty Publications

The high level of sparsity in methylome profiles obtained using whole-genome bisulfite sequencing in the case of low biological material amount limits its value in the study of systems in which large samples are difficult to assemble, such as mammalian preimplantation embryonic development. The recently developed computational methods for addressing the sparsity by imputing missing have their limits when the required minimum data coverage or profiles of the same tissue in other modalities are not available. In this study, we explored the use of transfer learning together with Kullback-Leibler (KL) divergence to train predictive models for completing methylome profiles with …

Pocket2drug: An Encoder-Decoder Deep Neural Network For The Target-Based Drug Design, W T. Shi, M Singha, G Srivastava, L M. Pu, W T. Shi, M Brylinski

Faculty Publications

Computational modeling is an essential component of modern drug discovery. One of its most important applications is to select promising drug candidates for pharmacologically relevant target proteins. Because of continuing advances in structural biology, putative binding sites for small organic molecules are being discovered in numerous proteins linked to various diseases. These valuable data offer new opportunities to build efficient computational models predicting binding molecules for target sites through the application of data mining and machine learning. In particular, deep neural networks are powerful techniques capable of learning from complex data in order to make informed drug binding predictions. In …

Glutamic-Oxaloacetic Transaminase 2 (Got2) Reverse Reaction Could Act As A Possible Relief Valve For Mitochondrial Substrate Overload Induced By Glucocorticoids, Humza Pirzadah

Honors Capstones

No abstract provided.

Citations Versus Expert Opinions: Citation Analysis Of Featured Reviews Of The American Mathematical Society, Lawrence Smolinsky, Daniel S. Sage, Aaron J. Lercher, Aaron Cao

Faculty Publications

Peer review and citation metrics are two means of gauging the value of scientific research, but the lack of publicly available peer review data makes the comparison of these methods difficult. Mathematics can serve as a useful laboratory for considering these questions because as an exact science, there is a narrow range of reasons for citations. In mathematics, virtually all published articles are post-publication reviewed by mathematicians in Mathematical Reviews (MathSciNet) and so the data set was essentially the Web of Science mathematics publications from 1993 to 2004. For a decade, especially important articles were singled out in Mathematical Reviews …

Expression, Purification, And Glycosylation Of Epidermal Growth Factor-Like Repeat 27 From Mouse Notch1, Justin A. Grennell, Kendra D. Jenkins, Huimin Zhong, Amid Paudyal, Kelvin B. Luther, Robert S. Haltiwanger, Megan A. Macnaughtan

Faculty Publications

© 2020 Elsevier Inc. Notch receptors have large extracellular domains containing up to 36 tandem epidermal growth factor-like (EGF) repeats, which facilitate cell signaling by binding ligands on neighboring cells. Notch receptors play major roles in a variety of developmental processes by controlling cell fate decisions. Each EGF repeat consists of about 40 amino acids with 3 conserved disulfide bonds. Many of the EGF repeats are modified by O-linked fucose glycans, and more than half have calcium-binding sites, but the sequences of the EGF repeats vary giving distinct roles to each repeat. EGF repeat 27 (EGF27) from mouse NOTCH1 is …

Point-Of-Care Devices For Therapeutic, Medical And Environmental Applications, Alisha Prasad

LSU Doctoral Dissertations

Point-of-care testing (POCT) or Point-of-use (POU) devices or technologies are defined as testing aids that are capable for onsite use or testing. The key advantages of POCT are low sample volume, quick onsite diagnosis, high accuracy, and cost-effectiveness. POCT has the potential and the benefits to facilitate better health care management by rapid routine diagnosis and monitoring. To reach this goal, several researchers as well as the healthcare industry over a few years have conducted cutting edge research to bring science to technology by developing smart diagnostic devices capable of performing as per patient profiles and make personalized health care …

Synthesis, Characterization, And Investigation Of Metal Ion Quenching In Fluorescent Carbon Dot Surrogates For Particulate Matter Black Carbon And Evaluation Of Cellular Health Effects Due To The Surrogate Materials, Christopher Lee Sumner Jr

LSU Doctoral Dissertations

Black carbon (BC) is an environmental pollutant of particular concern to many international organizations for both its health effects and environmental effects. Probing health effects of BC as produced in the environment is difficult due to the complex nature of environmental pollutants found in their naturally occurring state. Fluorescent carbon dots (FCDs) were chosen to be used as a surrogate for BC. In the process of examining FCDs and their behavior as surrogates, information was gained on the health effects and behavior of FCDs as a class of nanomaterials for cell and tissue studies, which is outlined in this dissertation. …

Bionoinet: Ligand-Binding Site Classification With Off-The-Shelf Deep Neural Network, Wentao Shi, Jeffrey M. Lemoine, Abd El Monsif A. Shawky, Manali Singha, Limeng Pu, Shuangyan Yang, J. Ramanujam, Michal Brylinski

Faculty Publications

© The 2020 Author(s). Published by Oxford University Press. All rights reserved. Motivation: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide-and …

A Pomc-Originated Circuit Regulates Stress-Induced Hypophagia, Depression, And Anhedonia, Na Qu, Yanlin He, Chunmei Wang, Pingwen Xu, Yongjie Yang, Xing Cai, Hesong Liu, Kaifan Yu, Zhou Pei, Ilirjana Hyseni, Zheng Sun, Makoto Fukuda, Yi Li, Qing Tian, Yong Xu

Division of Basic Science Faculty Publications

Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMCARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DAVTA neurons). We further revealed that POMCARH neurons project to the VTA and provide an inhibitory tone to DAVTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMCARH→VTA circuit in mice increases body weight and food intake, …

A Deda Family Membrane Protein Is Required For Burkholderia Thailandensis Colistin Resistance, Pradip R. Panta, Sujeet Kumar, Caroline F. Stafford, Caitlin E. Billiot, Martin V. Douglass, Carmen M. Herrera, M. Stephen Trent, William T. Doerrler

Faculty Publications

© Copyright © 2019 Panta, Kumar, Stafford, Billiot, Douglass, Herrera, Trent and Doerrler. Colistin is a “last resort” antibiotic for treatment of infections caused by some multidrug resistant Gram-negative bacterial pathogens. Resistance to colistin varies between bacterial species. Some Gram-negative bacteria such as Burkholderia spp. are intrinsically resistant to very high levels of colistin with minimal inhibitory concentrations (MIC) often above 0.5 mg/ml. We have previously shown DedA family proteins YqjA and YghB are conserved membrane transporters required for alkaline tolerance and resistance to several classes of dyes and antibiotics in Escherichia coli. Here, we show that a DedA family …

Age And Growth Of Hardhead Catfish And Gafftopsail Catfish In Coastal Louisiana, Usa, Shane Flinn, Stephen Midway

Faculty Publications

The Hardhead Catfish Ariopsis felis and Gafftopsail Catfish Bagre marinus are marine catfishes that have low recreational and commercial landings in U.S. waters, although they are among the most abundant species in coastal waters of the Gulf of Mexico. Few biological studies exist on marine catfishes, with most studies focusing on their unique reproductive biology. This study evaluated weight-length relationships for Gafftopsail Catfish (n = 264) and Hardhead Catfish (n = 823) sampled from across coastal Louisiana, USA, during 2016-2018; subsamples (93 and 266, respectively) were aged using lapilli for age and growth analyses. Hardhead Catfish showed a small but …

Near Infrared Gumbos And Nanogumbos For Biomedical Applications, Mi Chen

LSU Doctoral Dissertations

Recent advances in development of nanomaterials have provided great opportunities for cancer research. In this dissertation, nanoGUMBOS derived from a group of uniform materials based on organic salts (GUMBOS) were investigated for several biomedical applications including chemotherapy, photothermal therapy (PTT), and drug delivery. GUMBOS are solid-phase organic salts consisting of bulky cations and anions. Similar to ionic liquids, GUMBOS display highly tunable properties with counter-ions variation, but with a defined melting point range of 25–250 °C. Nanomaterials derived from GUMBOS, i.e. nanoGUMBOS, display enhanced properties at the nanoscale level. This dissertation focuses on development of near infrared IR780 nanoGUMBOS for …

A Gradient Of Pollination Specialization In Three Species Of Bolivian Centropogon, Laura P. Lagomarsino, Nathan Muchhala

Faculty Publications

© 2019 Botanical Society of America Premise: Closely related plant species with overlapping ranges often experience competition for pollination services. Such competition can select for divergence in floral traits that attract pollinators or determine pollen placement. While most species in Centropogon (Campanulaceae: Lobelioideae) have flowers that suggest adaptation to bat or hummingbird pollination, actual pollinators are rarely documented, and a few species have a mix of traits from both pollination syndromes. We studied the pollination biology of a “mixed-syndrome” species and its co-occurring congeners to examine the relationship between floral traits and visitation patterns for Centropogon. Methods: Fieldwork at two …

Bed Bugs (Cimex Lectularius L.) Exhibit Limited Ability To Develop Heat Resistance, Aaron R. Ashbrook, Michael E. Scharf, Gary W. Bennett, Ameya D. Gondhalekar

Faculty Publications

The global population growth of the bed bug, Cimex lectularius (L.), is attributed to their cryptic behavior, diverse insecticide resistance mechanisms, and lack of public awareness. Bed bug control can be challenging and typically requires chemical and non-chemical treatments. One common non-chemical method for bed bug management is thermal remediation. However, in certain instances, bed bugs are known to survive heat treatments. Bed bugs may be present after a heat treatment due to (i) abiotic factors associated with the inability to achieve lethal temperatures in harborage areas for a sufficient time period, (ii) re-infestation from insects that escaped to cooler …

Prediction Of Ice-Free Conditions For A Perennially Ice-Covered Antarctic Lake, M. K. Obryk, P. T. Doran, J. C. Priscu

Faculty Publications

©2019. American Geophysical Union. All Rights Reserved. Although perennially ice-covered Antarctic lakes have experienced variable ice thicknesses over the past several decades, future ice thickness trends and associated aquatic biological responses under projected global warming remain unknown. Heat stored in the water column in chemically stratified Antarctic lakes that have middepth temperature maxima can significantly influence the ice thickness trends via upward heat flux to the ice/water interface. We modeled the ice thickness of the west lobe of Lake Bonney, Antarctica, based on possible future climate scenarios utilizing a 1D thermodynamic model that accounts for surface radiative fluxes as well …

A Hydrodynamic Model For Galveston Bay And The Shelf In The Northern Gulf Of Mexico, J. Du, K. Park, J. Shen, Y.J. Zhang, X. Yu, F. Ye, Z. Wang, N.N. Rabalais

Faculty Publications

No abstract provided.