Biotechnology Commons^™

Deep Learning Prediction Of Chemical-Induced Dose-Dependent And Context-Specific Multiplex Phenotype Responses And Its Application To Personalized Alzheimer’S Disease Drug Repurposing, You Wu, Qiao Liu, Yue Qiu, Lei Xie

Publications and Research

Predictive modeling of drug-induced gene expressions is a powerful tool for phenotype-based compound screening and drug repurposing. State-of-the-art machine learning methods use a small number of fixed cell lines as a surrogate for predicting actual expressions in a new cell type or tissue, although it is well known that drug responses depend on a cellular context. Thus, the existing approach has limitations when applied to personalized medicine, especially for many understudied diseases whose molecular profiles are dramatically different from those characterized in the training data. Besides the gene expression, dose-depen- dent cell viability is another important phenotype readout and is …

Pengaruh Konsentrasi Benzylaminopurine Terhadap Pertumbuhan Eksplan Tunas Aksilar Rami Klon Lokal Wonosobo Secara In Vitro, Anne Nuraini, Eva Aprilia, Murgayanti, Asri Peni Wulandari

Jurnal Kultivasi

Saat ini, perbanyakan rami menggunakan rizoma sebagai bahan tanamnya, tetapi dalam produksinya membutuhkan waktu yang lama dan sebagai bahan tanam umur simpannya singkat. Kultur jaringan merupakan salah satu teknologi untuk mendapatkan bahan tanam yang seragam dan sehat dalam waktu yang singkat. Tujuan dilakukannya penelitian ini adalah untuk mengetahui pengaruh konsentrasi BAP terhadap pertumbuhan tunas aksilar pada rami klon lokal Wonosobo dan konsentrasi mana yang memberikan pengaruh terbaik. Percobaan dilakukan di Laboratorium Kultur Jaringan, Teknologi Benih, Fakultas Pertanian, Universitas Padjadjaran. Nodus batang dari rami klon lokal Wonosobo diklturkan pada media MS dengan penambahan berbagai konsentrasi BAP selama 8 minggu dan diamati …

Efektifitas Perbedaan Konsentrasi Bap Terhadap Pertumbuhan Planlet Pisang Cavendish Dengan Teknik Thin Cells Layer, Hidayati Karamina, Edyson Indawan, Fila Isti Kumala Agustina

Jurnal Kultivasi

Pisang murupakan komoditi dengan produksi paling tinggi di antara buah-buahan lainnya. Salah satu pisang yang diminati ialah Pisang Cavendish (Musa acuminata L.), namun pembibitan secara konvensional kurang memenuhi permintaan pasar. Salah satu alternatif untuk meningkatkan jumlah bibit pisang Cavendish adalah dengan perbanyakan tanaman secara in vitro. Teknik thin cell layer (TCL) merupakan teknik dalam kultur jaringan dengan mengiris tipis bagian tanaman yang dapat memperbanyak jumlah tunas planlet pisang Cavendish. Penelitian ini bertujuan untuk mengetahui konsentrasi BAP yang cocok untuk pertumbuhan planlet pisang Cavendish dengan menggunakan teknik TCL. Penelitian ini menggunakan rancangan acak lengkap (RAL) dengan 5 perlakuan dan 5 ulangan. …

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Department of Biochemistry: Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

Spatial Charting Of Single-Cell Transcriptomes In Tissues, Runmin Wei, Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Alastair Thompson, Ken Chen, Savitri Krishnamurthy, Nicholas E Navin

Faculty, Staff and Student Publications

Single-cell RNA sequencing methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, spatial transcriptomics assays can profile spatial regions in tissue sections, but do not have single-cell resolution. Here, we developed a computational method called CellTrek that combines these two datasets to achieve single-cell spatial mapping through coembedding and metric learning approaches. We benchmarked CellTrek using simulation and in situ hybridization datasets, which demonstrated its accuracy and robustness. We then applied CellTrek to existing mouse brain and kidney datasets and showed that CellTrek can detect topological patterns of different cell types and cell states. We …

Tau-Dependent Neurodegeneration And Alleviation By Etas®50, Clifford Tyree Castleberry

Theses (2016-Present)

Brain growth factors are a broad group of molecules that enable the brain to adapt to stress. In a study on Alzheimer’s mice (APP), we tested the role of an asparagus supplement, ETAS®50, to mitigate the stress caused by the Alzheimer’s condition in this mouse model. Gene expression data revealed regulation of genes related to neuronal growth and function, such as tau, which were severely stressed in the APP mice to be alleviated.

Application In Medicine: Has Artificial Intelligence Stood The Test Of Time, Mir Ibrahim Sajid, Shaheer Ahmed, Usama Waqar, Javeria Tariq, Mohsin Chundrigar, Samira Shabbir Balouch, Sajid Abaidullah

Medical College Documents

Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers …

Performance Of Machine Learning Classifiers In Classifying Stunting Among Under-Five Children In Zambia, Obvious Nchimunya Chilyabanyama, Roma Chilengi, Roma Chilengi, Michelo Simuyandi, Caroline C. Chisenga, Masuzyo Chirwa, Kalongo Hamusonde, Rakesh Kumar Saroj, Najeeha Talat Iqbal, Innocent Ngaruye

Department of Paediatrics and Child Health

Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) classification algorithms on the Zambia Demographic Health Survey (ZDHS) dataset to predict stunting among children under the age of five in Zambia. We applied Logistic regression (LR), Random Forest (RF), SV classification (SVC), XG Boost (XgB) and Naïve Bayes (NB) algorithms to predict the probability of stunting among children under five years of age, on the 2018 ZDHS dataset. We calibrated predicted probabilities and plotted the calibration curves to compare model performance. We computed accuracy, recall, precision and F1 for each machine learning algorithm. …

Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee

Engineering Science Faculty Publications

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …

Methanogen Metabolic Flexibility, Sean R. Carr

School of Biological Sciences: Dissertations, Theses, and Student Research

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta

Department of Biochemistry: Faculty Publications

Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly …

Functional Requirements For A Samd14-Capping Protein Complex In Stress Erythropoiesis, Suhita Ray, Linda Chee, Yichao Zhou, Meg A. Schaefer, Michael J. Naldrett, Sophie Alvarez, Nicholas T. Woods, Kyle J. Hewitt

Nebraska Center for Biotechnology: Faculty and Staff Publications

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals—involving cooperation between stem cell factor (SCF)/Kit signaling and other signaling inputs—are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the sterile alpha motif (SAM) domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling. However, the mechanism underlying Samd14’s role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and β-heterodimers of the F-actin capping protein (CP) complex. Knockdown of …

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth …

Dairy By-Product Derived Cardioprotective Lipids, Hannah Ring

ORBioM (Open Research BioSciences Meeting)

Background: Atherosclerosis is a chronic inflammatory disorder, characterised by the accumulation of plaque on the walls of the arteries. Rupture of this plaque often results in life threatening clinical complications such as heart attack and stroke, which currently are the two leading causes of global mortality. Dietary guidelines usually condemn the consumption of whole fat dairy products due to their saturated fat content and this ingredient’s association with cholesterol and cardiovascular diseases, such as atherosclerosis. This viewpoint however, is dated and controversial as much data is emerging on the cardiometabolic benefits of polar lipids found in dairy products which are …

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and …

Dj-1 Is Not A Deglycase And Makes A Modest Contribution To Cellular Defense Against Methylglyoxal Damage In Neurons, Melissa Conti Mazza, Sarah C. Shuck, Jiusheng Lin, Michael Moxley, John Termini, Mark R. Cookson, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redox-regulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how …

Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter

Dissertations

ABSTRACT

RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …

Optimization Of Palmitic Acid Production In Chloroidium Sp. Utex 3007 As A Sustainable Source Of Palm Oil Alternative, Amnah Salem Alzahmi

Theses

The increase in palm oil consumption and production has resulted in removing up to 90% of trees in some tropical forests. The green microalgae Chloroidium sp. UTEX 3007 can be an alternative sustainable source of palm oil due to its high palmitic acid content. The objective of this study was to generate a mutant Chloroidium population that is capable of producing and accumulating elevated levels of palmitic acid and to characterize the obtained populations’ lipid contents. The palmitic acid production optimization in Chloroidium sp. UTEX 3007 was conducted via a workflow of ultraviolet (UV) mutagenesis and sorting of high-lipid producing …

Altered Collective Mitochondrial Dynamics In The Arabidopsis Msh1 Mutant Compromising Organelle Dna Maintenance, Joanna M. Chustecki, Ross D. Etherington, Daniel J. Gibbs, Iain G. Johnston

Department of Biochemistry: Faculty Publications

Mitochondria form highly dynamic populations in the cells of plants (and almost all eukaryotes). The characteristics and benefits of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently developed quantitative approach to reveal and analyse the physical and collective ‘social’ dynamics of mitochondria in an Arabidopsis msh1 mutant where the organelle DNA maintenance machinery is compromised. We use a newly created line combining the msh1 mutant with mitochondrially targeted green fluorescent protein (GFP), and characterize mitochondrial dynamics with a combination of single-cell time-lapse microscopy, computational tracking, and network …

Biomass Estimation Of Marine Biofilms On Plastic Surfaces, Kian Banihashemi, Fernando Javier Gil

Biological Sciences

Plastics have become a major source of marine pollution, which threatens food safety and quality, human health, and marine ecosystems. Due to the drastic negative effects of plastics in a marine environment, alternative biodegradable plastics are being generated that are more eco-friendly and have less environmental impact. Though some of these plastics are known to biodegrade, the process of degradation for bioplastics has not been heavily studied in a marine environment. This pilot project sought to both quantify the process of biodegradation and compare across different methods for effectiveness of biomass estimation, which serves as an indicator of biodegradation. Plastics …

Rhizosphere-Competent Actinobacterial Isolates With Acc Deaminase Activity Alleviate Salt Stress In Tomato Plants In The Uae, Alaa Ahmed Abbas Elbadawi

Biology Theses

Tomato (Solanum lycopersicum) is one of the most popular vegetables in the world, including the United Arab Emirates (UAE). Salinity is a global menace to plant growth and development, causing significant economic losses to tomato and other crop plants. It is well-known that 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase (ACCD) can increase plant tolerance to environmental stresses. This can be attributed to the increased activity of the enzyme ACCD, which breaks down ACC [the immediate precursor of ethylene (ET)] to ammonia and α-ketobutyrate, to lower the overproduction of ET levels in planta and to reduce the damages caused …

Development Of Optical Nanomaterial For Enhanced Cerenkov Imaging, Qize Zhang

Dissertations, Theses, and Capstone Projects

Cancer is a significant public health problem worldwide and is the second leading cause of death in the United States. Imaging has increasingly been used over the last two decades to improve the diagnosis and guidance of tumor tissue removal surgery. Among the most widely used techniques for in vivo imaging are planar and tomographic fluorescence imaging and bioluminescence imaging. Despite their utility, these techniques are primarily restricted to preclinical use. Factors that have prevented translation from the bench to the bedside include depth-penetration considerations, regulatory issues, and toxicity. A recent development in nuclear imaging has been the ability to …

In Silico Identification Of Potential Inhibitors Of The Sars‑Cov‑2 Nucleocapsid Through Molecular Docking‑Based Drug Repurposing, Rukhsar Afreen, Saleem Iqbal, Ab Rauf Shah, Heena Afreen, Maitreyi College, Mohd. Shkir

Department of Biochemistry: Faculty Publications

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, and its effects on people worldwide continue to grow. Protein-targeted therapeutics are currently unavailable for this virus. As with other coronaviruses, the nucleocapsid (N) protein is the most conserved RNA-binding structural protein of SARS-CoV-2. The N protein is an appealing target because of its functional role in viral transcription and replication. Therefore, molecular docking method for structure-based drug design was used to investigate the binding energy and binding modes of various anti-N inhibitors in depth. The inhibitors selected were originally developed to target stress granules and other molecules involved in RNA …

Producing Bacterial Cellulose From Coffee (Coffea Arabica) Kombucha Fermentation And Assessment Of Its Efficacy To Remove Pathogenic Bacteria From Contaminated Water And A Pollutant Dye From Aqueous Solution, Federico Bueno

LSU Doctoral Dissertations

Bacterial cellulose (BC), composed of cellulosic nanofibrils, is synthesized by a symbiotic culture of bacteria and yeast during the fermentation of coffee kombucha (CK). BC may be used as a purification agent and adsorbent. The overall goal of this project was to synthesize BC from CK fermentation and assess its efficacy in removing pathogenic bacteria from contaminated water and a pollutant dye from aqueous solution. The objectives of this study were to: (1) compare BCs that were produced from different carbohydrate substrates in the fermentation of CK, (2) characterize dried BCs produced using various drying methods, (3) evaluate BC as …

Guard-Cell-Targeted Overexpression Of Arabidopsis Hexokinase 1 Can Improve Water Use Efficiency In Field-Grown Tobacco Plants, Liana G. Acevedo-Siaca, Katarzyna Glowacka, Steven M. Driever, Coralie E. Salesse-Smith, Nitsan Lugassi, David Granot, Stephen P. Long, Johannes Kromdijk

Department of Biochemistry: Faculty Publications

Water deficit currently acts as one of the largest limiting factors for agricultural productivity worldwide. Additionally, limitation by water scarcity is projected to continue in the future with the further onset of effects of global climate change. As a result, it is critical to develop or breed for crops that have increased water use efficiency and that are more capable of coping with water scarce conditions. However, increased intrinsic water use efficiency (iWUE) typically brings a trade-off with CO₂ assimilation as all gas exchange is mediated by stomata, through which CO₂ enters the leaf while water vapor exits. …

Isolation And Characterization Of Α-Hcd7 Scfv Expressing Exosomes And Synthesis Of Hybrid Exosome-Liposome For Analyses, Sahil Patel

Biotechnology Theses

The goal of this thesis project is to isolate and characterize exosomes that express anti-human CD7 (α-hCD7) single chain variable fragment (scFv), which will be further utilized for T celltargeted gene editing. To reach this goal, exosomes from HEK 293 cells and Jurkat cells were isolated and characterized with different methodologies. To obtain α-hCD7 scFv-expressing exosomes, the HEK 293 cells were subjected to transfection of custom-plasmid pDisplay-αhCD7 scFv, and the expression of α-hCD7 scFv on the HEK 293-derived exosomes were then confirmed by immunogold staining, western blotting, and flow cytometry. To transfect 293 cells, calcium phosphate transfection was utilized, and …