Biotechnology Commons^™

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Enhancing Crop Resilience: Physiological And Omics Approaches For Drought And Heat Stress Tolerance In Soybean And Peanut, Jyoti Prasad Kakati

All Dissertations

Soybean and peanut are two major crops globally grown for oil and protein. Climate change-associated factors like drought and increased temperature (heat stress) challenge the global production of soybeans and peanuts. Though the United States is the second-largest producer of soybean and the fourth-largest producer of peanuts, it still faces production constraints associated with drought and heat stresses. In the present study, we have examined the responses of soybean and peanut plants to drought and heat stresses during germination and reproductive phases. We conducted field and controlled environmental studies to elucidate the impact of drought stress on germination and seedling …

Exploring Chilling Stress And Recovery Dynamics In C4 Perennial Grass Of Miscanthus Sinensis, Karolina Sobańska, Monika Mokrzycka, Martyna Przewoźnik, Tomasz Pniewski, Katarzyna Glowacka

Department of Biochemistry: Faculty Publications

The increasing cultivation of perennial C4 grass known as Miscanthus spp. for biomass production holds promise as a sustainable source of renewable energy. Unlike the sterile triploid hybrid of M. × giganteus, which cannot reproduce through seeds, M. sinensis possesses attributes that could potentially address these limitations by effectively establishing itself through seed propagation. This study aimed to investigate how 18 genotypes of M. sinensis respond to chilling stress and subsequent recovery. Various traits were measured, including growth and biomass yield, the rate of leaf elongation, and a variety of chlorophyll fluorescence parameters, as well as chlorophyll …

Ocular Gene Transfer In The Spotlight: Implications Of Newspaper Content For Clinical Communications, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of …

Five Side Populations Isolated From Rat Bone Marrow‑Derived Mesenchymal Stem Cells, Dalia Al Saied Moustafa Ahmed, Mahmoud Elhussiny Salama, Ahmed Abdou Emam, Sara Mohamed Farrag, Basma Hamed Othman, Shaimaa Hassan Haiba, Mohamed Mosaad Salama

Faculty Journal Articles

Over the past decade, there has been marked enthusiasm surrounding the potential application of mesenchymal stem cells (MSCs) as universally compatible donor cells in the field of regenerative medicine. Due to their distinctive immune-tolerant characteristics, these entities hold promise for potential applications in cell replacement, gene therapy and immunomodulatory therapy. MSCs have been defined and characterized based on adhesion properties and different surface markers that are negative for hematopoietic stem cells and positive for MSCs, and their capacity for differentiation into osteocyte, chondrocyte and adipocyte is observed under suitable circumstances. However, this protocol is costly and time-consuming and cannot confirm …

Type-2 Diabetes, Pancreatic Amylin, And Neuronal Metabolic Remodeling In Alzheimer's Disease, Noah Leibold, James R. Bain, Florin Despa

Neurology Faculty Publications

Type-2 diabetes raises the risk for Alzheimer’s disease (AD)-type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type-2 diabetes to AD remain largely unknown. Amylin, a pancreatic 𝜷-cell hormone co-secreted with insulin, participates in the central regulation of satiation, but also forms pancreatic amyloid in persons with type-2 diabetes and synergistically interacts with brain amyloid 𝜷 (A𝜷) pathology, in both sporadic and familial Alzheimer’s disease (AD). Growing evidence from studies of tumor growth, together with early observations in skeletal muscle, indicates amylin as a potential trigger of cellular metabolic reprogramming. Because the blood, cerebrospinal fluid, …

Diffuse Reflectance Spectroscopy For Optical Characterizations Of Orthotopic Head And Neck Cancer Models In Vivo, Pranto Soumik Saha, Jing Yan, Caigang Zhu

Markey Cancer Center Faculty Publications

We demonstrated an easy-to-build, portable diffuse reflectance spectroscopy device along with a Monte Carlo inverse model to quantify tissue absorption and scattering-based parameters of orthotopic head and neck cancer models in vivo. Both tissue-mimicking phantom studies and animal studies were conducted to verify the optical spectroscopy system and Monte Carlo inverse model for the accurate extraction of tissue optical properties. For the first time, we reported the tissue absorption and scattering coefficients of mouse normal tongue tissues and tongue tumor tissues. Our in vivo animal studies showed reduced total hemoglobin concentration, lower tissue vascular oxygen saturation, and increased tissue scattering …

Dynamic Metabolic Flux Analysis Amidst Data Variability: Sphingolipid Biosynthesis Case Study In Arabidopsis Thaliana Cell Cultures, Abraham Boluwatife Osinuga

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. In this study, we explore its de novo biosynthesis and homeostasis in Arabidopsis thaliana cell cultures, shedding light on fundamental metabolic mechanisms. Employing ¹⁵N isotope labeling and quantitative dynamic modeling approach, we obtained data with notable variations and developed a regularized and constraint-based Dynamic Metabolic Flux Analysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase …

Exploring The Coffee Genome: A Comprehensive Analysis Of The Plant-Specific Dof Transcription Factor Gene Family, Humera Amin, Shumaila Dastgir, Numan Ali, Muhammad Shafiq, Muhammad Haseeb, Syed Agha Armaghan Asad Abbas Naqvi, Laiba Sharif, Syeda Shehar Bano Rizvi, Sohaib Ahmad, Farooq Ahmad

Journal of Bioresource Management

Dof (DNA binding with one finger) proteins constitute highly ubiquitous transcription factor gene families that are found across all plant species, playing crucial role in fruit ripening, organ development, and other activities. A comprehensive genome-wide analysis of the coffee genome uncovered 49 CaDof genes, which were described in terms of their gene structures, phylogenetic relationships, subcellular localization, gene duplication, and expression in various plant organs. In Coffea arabica, segmental duplication outnumbered tandem duplication. Expressed sequence tags were used to determine the expression of specific organs in CaDof genes. Most genes showed high expression in fruits at various stages, in …

Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3), Jocelyn Nataniel, Maria Ulfah, Dini Achnafani, Niknik Nurhayati, Gabriela Christy Sabbathini, Sri Rezeki Wulandari, Abinawanto Abinawanto, Is Helianti

Makara Journal of Science

The waste of polyethylene terephthalate (PET) plastic waste in Indonesia is a pressing concern due to its slow degradation and potential environmental damage. One promising solution is to utilize polyethylene terephthalate hydrolase from Ideonella sakaiensis (IsPETase), an enzyme that specifically degrades PET. However, inducing the expression of IsPETase synthetic gene in Escherichia coli BL21 (DE3) has been challenging because much of it remains insoluble. This study aimed to express IsPETase in E. coli Arctic Express (DE3) and optimize the conditions to enhance its production. First, pET22b(+)pelB-IsPETase was inserted into E. coli Arctic Express (DE3). The …

Cultivation Of Chlorella And Chlamydomonas Under Nitrogen Starvation Conditions: Research Of Fatty Acids Production Potential, Affaf Kord, Samira Chader, Maha Kherrarba, Soumia Benrabah

Journal of Bioresource Management

Microalgae are attracting particular attention because of their use in various fields such as bio-energy. The main objective of this work was to evaluate the effect of stress induced by nitrogen deficiency on the accumulation of lipids in Chlorella sp. and Chlamydomonassp. isolated from the brackish water of El Golea Lake in the Algerian Sahara. The two species were first cultured in batch in BBM medium under basic conditions (0.75 g/l NaNO

₃

) then under nitrogen stress (0.25 g/l NaNO

₃

). After lipids extraction, the fatty acids were trans-esterified to obtain the fatty acid methyl esters that …

Structural And Biophysical Insights Into Targeting Of Claudin-4 By A Synthetic Antibody Fragment, Satchal K. Erramilli, Pawel K. Dominik, Chinemerem P. Ogbu, Anthony A. Kossiakoff, Alex J. J.

Department of Biochemistry: Faculty Publications

Claudins are a 27-member family of ~25 kDa membrane proteins that integrate into tight junctions to form molecular barriers at the paracellular spaces between endothelial and epithelial cells. As the backbone of tight junction structure and function, claudins are attractive targets for modulating tissue permeability to deliver drugs or treat disease. However, structures of claudins are limited due to their small sizes and physicochemical properties—these traits also make therapy development a challenge. Here we report the development of a synthetic antibody fragment (sFab) that binds human claudin-4 and the determination of a high-resolution structure of it bound to claudin-4/enterotoxin complexes …

Deciphering The Microbial Fingerprint Of Covid-19: A Multi-Layered Exploration Of The Oral And Gut Microbiome Dysbiosis, Iman Mostafa Sultan

Theses and Dissertations

The impact of SARS-CoV-2 infection on the human microbiome remains a dynamic and intricate puzzle. This study delves deeper into this mystery by revisiting the oral and gut microbial compositions of 53 COVID-19 patients before and after viral clearance, alongside comparisons to 76 healthy individuals. Through a comparative lens, we have emploed two distinct differential abundance methods – DeSeq2 and ANCOM – while drawing upon the thorough SILVA database encompassing the full-length 16S rRNA gene. The analysis underscores the crucial role of a diverse methodological choir in microbiome research. In certain instances, the congruence between DeSeq2 and ANCOM may exhibit …

Cytotoxicity, Antibacterial And Anti-Inflammatory Properties Of A Synthesized Curcumin Analog And One Of Its Novel Derivatives, Marian Amir

Theses and Dissertations

This research aims to describe the synthesis, characterization, and the biological response via investigating the cytotoxic activity, hypoxic microenvironment response, antibacterial, and anti-inflammatory properties of the novel curcumin analog H-4073 and its succinate derivative (H-4073 SuD) in the context of hepatocellular carcinoma (HCC). The study also aimed to compare the effects of H-4073 and H-4073 SuD to assess their relative efficacy and potential as therapeutic agents. First, the cytotoxic effects of H-4073 and H-4073 SuD were evaluated on HEPG2 cell lines under normal conditions. Results revealed that H-4073 exhibited a significantly better cytotoxic effect than H-4073 SuD in normoxia. However, …

Perspectives On Computational Modeling Of Biological Systems And The Significance Of The Sysmod Community, Bhanwar Lal Puniya, Meghna Verma, Chiara Damiani, Shaimaa Bakr, Andreas Dräger

Department of Biochemistry: Faculty Publications

Motivation: In recent years, applying computational modeling to systems biology has caused a substantial surge in both discovery and practical applications and a significant shift in our understanding of the complexity inherent in biological systems.

Results: In this perspective article, we briefly overview computational modeling in biology, highlighting recent advancements such as multiscale modeling due to the omics revolution, single-cell technology, and integration of artificial intelligence and machine learning approaches. We also discuss the primary challenges faced: integration, standardization, model complexity, scalability, and interdisciplinary collaboration. Lastly, we highlight the contribution made by the Computational Modeling of Biological Systems …

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Naturify 2300, Yarina Yiwei Dai

Masters Theses

In my art practice, I explore the interplay between human desires to manipulate and anthropomorphize nature, as seen in the technological augmentation of plants and living entities. This investigation delves into how this intersection, alongside empathy towards these creations, contributes to fears of uncontrollability and the risks of addiction and excessive dependence on technology.

Bioengineering and genetic modification have cultivated unprecedented developments, allowing humans to manipulate the fundamental building blocks of life. My research speculates on this technology further, modifying the genetic code of organisms and creating bioengineered wearable entities with enhanced traits or entirely new functionalities. The primary objective …

Functional Characterization Of Potato Arp1 Gene Encoding Auxin-Repressed Protein, Sara Ali Alneyadi

Theses

Auxin-repressed proteins (ARPs) are conserved in higher plants and are involved in plant growth and development by controlling gene expression. ARP1 has been studied for its role in biotic stress response, but its role in abiotic stress response remains unclear. In this study, transgenic Arabidopsis plants expressing potato (S. tuberosum) ARP1 were evaluated for their salinity stress response. By gradually increasing NaCl concentrations from 0 to 200mM, plants were subjected to high salinity stress. As compared to wild-type (WT) control plants under stressed conditions, the ARP1 transgenic plants demonstrated improved height and root length and higher chlorophyll content. Under …