Biotechnology Commons^™

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 …

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, …

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 …

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 …

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 …

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 …

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 …

Innovation In Bioinformatics: Recent Tools, Database And Involvement Of Artificial Intelligence, Aziz Ahmed, Mohd Shuaib, Abdulbasid Banga, Rizwan Ahmad

Indonesian Journal of Medical Chemistry and Bioinformatics

Bioinformatics has evolved in recent years into a crucial subject and a well-liked research area that is interconnected with many approaches and disciplines. The capacity of bioinformatics and its approaches to tackle challenging biological problems and promote research and development. There are various tools and database which are used in bioinformatics. AI is the capacity of a computational system to carry out various activities associated with intellectual beings and as a computer system's imitation of human intelligence processes. The bioinformatics applications with artificial intelligence have the capacity to annotate the data in the direction of logical conclusions. By combining AI …

Novel Role And Mechanisms Of Brd4 In Mediating Mesothelial To Mesenchymal Transition And Pleural Fibrosis, Felix Kankam

Biotechnology Theses

Pleural fibrosis is characterized by myofibroblast accumulation and increased expression of collagen and other extracellular matrices due to injury to the pleura and remodeling. Mesothelial to mesenchymal transition (MesoMT) is an important pathological event that contributes to the pool of myofibroblasts although its regulation remains incompletely understood. Recent research has reported the role of BRD4, a member of the bromodomain extra terminal domain (BET) family, in developing fibrosis in the heart and the lungs. One recent study showed that MEOX1 is a downstream target of BRD4 and mediated cardiac fibroblast activation. Our joint work also demonstrated that NOX4 is implicated …

Descspim: An Affordable And Easy-To-Build Light-Sheet Microscope Optimized For Tissue Clearing Techniques, Kohei Otomo, Takaki Omura, Yuki Nozawa, Steven J. Edwards, Yukihiko Sato, Yuri Saito, Shigehiro Yagishita, Hitoshi Uchida, Yuki Watakabe, Kiyotada Naitou, Rin Yanai, Naruhiko Sahara, Satoshi Takagi, Ryohei Katayama, Yusuke Iwata, Toshiro Shiokawa, Yoku Hayakawa, Kensuke Otsuka, Haruko Watanabe-Takano, Yuka Haneda, Shigetomo Fukuhara, Miku Fujiwara, Takenobu Nii, Chikara Meno, Naoki Takeshita, Kenta Yashiro, Juan Marcelo Rosales Rocabado, Masaru Kaku, Tatsuya Yamada, Yumiko Oishi, Hiroyuki Koike, Yinglan Cheng, Keisuke Sekine, Jun-Ichiro Koga, Kaori Sugiyama, Kenichi Kimura, Fuyuki Karube, Hyeree Kim, Ichiro Manabe, Tomomi Nemoto, Kazuki Tainaka, Akinobu Hamada, Hjalmar Brismar, Etsuo A. Susaki

Department of Biochemistry: Faculty Publications

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktopequipped SPIM for cleared specimens), a low-cost ($20,000–50,000), lowexpertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a threedimensional manner. Academically open-sourced (https://github.com/dbsbjuntendo/ …

Multifaceted Roles Of Meg3 In Cellular Senescence And Atherosclerosis, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Vijaya Bhaskar Baki, Matthew Moran, Huabo Su, Xinghui Sun

Department of Biochemistry: Faculty Publications

Background and aims: Long noncoding RNAs are involved in the pathogenesis of atherosclerosis. As long non-coding RNAs maternally expressed gene 3 (Meg3) prevents cellular senescence of hepatic vascular endothelium and obesity-induced insulin resistance, we decided to examine its role in cellular senescence and atherosclerosis.

Methods and Results: By analyzing our data and human and mouse data from the Gene Expression Omnibus database, we found that Meg3 expression was reduced in humans and mice with cardiovascular disease, indicating its potential role in atherosclerosis. In Ldlr^−/− mice fed a Western diet for 12 weeks, Meg3 silencing by chemically modified …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Utilizing Biomimicry To Design Sustainable Architecture, Virginia Hammond

Architecture Undergraduate Honors Theses

Nature has an integral relationship with architecture and serves as a sustainable role model and inspiration for designers. The process of biomimicry in architecture has the potential to produce more sustainable design solutions and foster a connection between humans and nature. Existing biomimetic design projects have varying strengths and weaknesses as examples of the process. Utilizing guidelines and references from key leaders in biomimetic design consultancy (Biomimicry 3.8), selected case studies are assessed for their ability to demonstrate the benefits of this design strategy. Using these evaluations, the case studies are diagrammed and critiqued to determine how new projects could …

Transcriptomic Profiling Of Engineered Human Gene Integration In The Mouse Genome Following In Vitro Gene Editing, Ethan Potts, Made Harumi Padmaswari, Christopher Nelson

Biomedical Engineering Undergraduate Honors Theses

Gene replacement is a promising method of therapy for genetic diseases. However, safety and efficacy are areas that need more research. This experiment aims to use RNA sequencing and bioinformatic techniques to provide answers to these questions and provide direction to future studies to develop a gene replacement therapeutic. C2C12 mouse myoblast cells were transfected with a vector containing a CRISPR-Cas9 system and the Human Factor IX (hF9) gene in order to hijack target genes and integrate the hF9 gene. The two target genes, myoglobin (Mb) and creatine kinase (Ckm), were chosen for their high rate of expression and low …

Determining The Impacts Of Corn Silage Mixing Ratios On Hydrogen Production From Beef Cattle Manure, Katya Faber-Quimby

Honors Program: Senior Projects (Public)

With global warming becoming an increasingly serious threat and a growing population requiring additional energy resources, interest in the production of clean energy from the agricultural sector has surged in popularity. Biohydrogen, also known as green hydrogen, is H₂ that has been produced using renewable energy, such as from agricultural byproducts or waste materials. It presents a promising alternative to nonrenewable resources due to its high potential for energy storage and lack of carbon emissions when used. Cattle manure has been explored as a resource for the production of biohydrogen. Selecting for hydrogen-producing microbes in the manure serves the …

Broadening The Application Range Of Cell-Free Protein Expression Systems, Matthew Becker

All Theses

Centralized protein manufacturing platforms make the delivery of needed therapies to places with limited infrastructure almost impossible. Cell-free protein expression systems, systems that utilize protein production machinery extracted from cells, offer these communities a viable protein expression platform that is robust and easily deliverable to the place of need. Much work in cell-free system engineering looks to increase the hardiness of cell-free system (CFS) components, like the extract and reaction buffer, needed to carry transcription and translation of gene therapeutic targets forward. Freeze- and air-drying of extract, reaction buffer, or both with certain additives, like sugar molecules, has been proposed …

Bootstrapping For Estimating The Conservative Kill Ratio Of The Surrogate To The Pathogen For Use In Thermal Process Validation At The Industrial Scale, Arshpreet Kaur Khattra, Surabhi Wason, Kevin Thompson, Andy Mauromostakos, Jeyamkondan Subbiah, Jennifer C. Acuff

Food Science Faculty Publications and Presentations

A surrogate is commonly used for process validations. The industry often uses the target log cycle reduction for the test (LCR_Test) microorganism (surrogate) to be equal to the desired log cycle reduction for the target (LCR_Target) microorganism (pathogen). When the surrogate is too conservative with far greater resistance than the pathogen, the food may be overprocessed with quality and cost consequences. In aseptic processing, the Institute for Thermal Processing Specialists recommends using relative resistance (D_Target)/(D_Test) to calculate LCR_Test (product of LCR_Target and relative resistance). This method uses the mean values …

Locally Injectable Peptide Hydrogel For Conversion Of Temozolomide And Codelivery Of Sirna In Glioblastoma Multiforme Treatment, Megan Pitz

All Dissertations

Traditional treatment methods for glioblastoma multiforme (GBM) are largely unsuccessful, with a 5-year survival rate of 5.6%. Temozolomide (TMZ), the only chemotherapy FDA-approved for GBM treatment, is a hydrophobic prodrug that is stable in an acidic pH and begins converting to its active form at a physiological pH of 7.4. However, complete conversion of TMZ is observed only at a higher pH, and only about 30% of administered TMZ reaches the central nervous system. Therefore, there is a need for new treatment methods that maximize TMZ delivery to and efficacy at the tumor site. Self-assembling peptides are a unique class …

Qualitative Assessment Of Human Embryonic- And Induced Pluripotent Stem Cell Derived Neural Stem Cells Under Cgmp Methods, Michelle Hernandez

Electronic Theses, Projects, and Dissertations

Neural stem cell therapies represent a promising tool for the development of regenerative medicine and are being tested in clinical trials for several neurological disorders. However, the clinical applicability of stem cell therapies is dependent on the implementation of current good manufacturing practices (cGMPs) to ensure the quality, safety, and consistency that stem cell products need to meet FDA regulatory requirements. As such, there is a need for a shift to xeno-free methodologies so experimental conditions are cGMP compliant. The purpose of this study is to test a GMP compatible production method to generate multipotent neural stem cells (NSCs) from …