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Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay

Dartmouth College Ph.D Dissertations

The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve …

Statistical Modeling Of Extracellular Vesicle Cargo To Predict Clinical Trial Outcomes For Hypoplastic Left Heart Syndrome, Jessica R Hoffman, Hyun-Ji Park, Sruti Bheri, Manu O Platt, Joshua M Hare, Sunjay Kaushal, Judith L Bettencourt, Dejian Lai, Timothy C Slesnick, William T Mahle, Michael E Davis

Journal Articles

Cardiac-derived c-kit+ progenitor cells (CPCs) are under investigation in the CHILD phase I clinical trial (NCT03406884) for the treatment of hypoplastic left heart syndrome (HLHS). The therapeutic efficacy of CPCs can be attributed to the release of extracellular vesicles (EVs). to understand sources of cell therapy variability we took a machine learning approach: combining bulk CPC-derived EV (CPC-EV) RNA sequencing and cardiac-relevant

In Silico Prediction Of Sodium-Glucose Co-Transporter-2 (Sglt2) Inhibition Activity By Allium Fistulosum Compound Based On Skelspheres Molecular Descriptor, Rudy Heryanto, Aryo Tedjo, Dimas Noor

Indonesian Journal of Medical Chemistry and Bioinformatics

The Sodium-Glucose co-transporter-2 (SGLT2) inhibitor represents a novel agent for the treatment of type 2 diabetes. Drugs of this class function by inhibiting glucose reabsorption in the kidneys, thereby controlling blood glucose levels. It is known that SGLT2 inhibitors activate the AMPK signaling pathway by increasing the expression and activity of AMP-activated protein kinase (AMPK). In vivo tests have demonstrated that ethanolic and aqueous extracts of Welsh onion leaves (Allium fistulosum L) can reduce body weight, liver weight, adipocyte size, and enhance AMP-activated protein kinase (AMPK) expression. In this study, the inhibitory activity (IC50) of compounds within Allium fistulosum against …

Fortifying Iot Against Crimpling Cyber-Attacks: A Systematic Review, Usman Tariq, Irfan Ahmed, Muhammad Attique Khan, Ali Kashif Bashir

Karbala International Journal of Modern Science

The rapid growth and increasing demand for Internet of Things (IoT) devices in our everyday lives create exciting opportunities for human involvement, data integration, and seamless automation. This fully interconnected ecosystem considerably impacts crucial aspects of our lives, such as transportation, healthcare, energy management, and urban infrastructure. However, alongside the immense benefits, the widespread adoption of IoT also brings a complex web of security threats that can influence society, policy, and infrastructure conditions. IoT devices are particularly vulnerable to security violations, and industrial routines face potentially damaging vulnerabilities. To ensure a trustworthy and robust security framework, it is crucial to …

Metabolomic Insights Into Tuberculosis: Machine Learning Approaches For Biomarker Identification, Miftahul Khair Akbar, Arief Aulia Rahman

Indonesian Journal of Medical Chemistry and Bioinformatics

The lung parenchyma is largely impacted by the infectious condition known as pulmonary tuberculosis (pulmonary TB) when the immune system creates a wall around the germs in the lungs, a tiny, hard bulge known as a tubercle develops, earning the disease the name tuberculosis. Although the majority of TB germs target the lungs, they can also harm other bodily organs. The identification of TB biomarkers, which are crucial for diagnosis, treatment monitoring, risk analysis, and prognosis, has been the subject of extensive research. Differences in metabolites between normal cells and tuberculosis are considered to be able to support the diagnosis …

Predicted Structure And Analysis Of The Glycoprotein From Sars-Cov-2 Variants Of Interest, Boris Shabaltiy

Honors Theses

SARS-CoV-2 has had a devastating effect on the world, and while the public concern and severity of the diseased caused by it have decreased, it is still crucial to monitor the virus for mutations so we can rapidly identify new variants of concern, and then rapidly prepare new vaccines and treatments. The SARS-CoV-2 spike (S) protein from the first isolates of the virus (root variant) was structurally characterized in early 2021. The spike protein structure, designated 7CZW, was uploaded to RCSB Protein Data Bank (RCSB PDB). All subsequent mutations the S protein has accumulated are based on the amino acid …

Biomechanical Adaptations While Performing Bilateral Drop Landings With A Unilateral Ankle Tape Application, Eric Daniel Jenkins

Rehabilitation Sciences Theses & Dissertations

Ankle sprains are the most common injury in sport and exercise performance, which makes the utilization of ankle taping a common procedure to both prevent potential sprain, as well as protect against reinjury. However, unilateral ankle taping may have unintended consequences on the mechanics of the ankle and other joints of both legs. The aim of this dissertation was to determine the effects of ankle taping on lower body kinetics and kinematics, stiffness, and coordination during a bilateral landing task.

Twelve female participants completed a total of 90 drop landings across two visits, randomized from landing platforms of 30, 45, …

Tracing And Segmentation Of Molecular Patterns In 3-Dimensional Cryo-Et/Em Density Maps Through Algorithmic Image Processing And Deep Learning-Based Techniques, Salim Sazzed

Computer Science Theses & Dissertations

Understanding the structures of biological macromolecules is highly important as they are closely associated with cellular functionalities. Comprehending the precise organization of actin filaments is crucial because they form the dynamic cytoskeleton, which offers structural support to cells and connects the cell’s interior with its surroundings. However, determining the precise organization of actin filaments is challenging due to the poor quality of cryo-electron tomography (cryo-ET) images, which suffer from low signal-to-noise (SNR) ratios and the presence of missing wedge, as well as diverse shape characteristics of actin filaments. To address these formidable challenges, the primary component of this dissertation focuses …

Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati

Research Symposium

Background: Kinases are enzymes that have proven to be important drug targets due to their role in critical biological mechanisms such as phosphorylation. Phosphorylation happens when a kinase catalyzes the transfer of a phosphate group to a protein in a phosphorylated site, which then becomes known as the substrate of the kinase. Any dysregulation of protein phosphorylation causes a wide range of complex diseases including cancer. Thus, discovering the links between kinases and their substrates (i.e. predicting kinase-substrate associations (KSAs)) is crucial in developing effective and sustainable treatments. Presently, less than 5% of phosphorylated sites have an associated kinase, and …

Exploration Of Potential Natural Inhibitors Against Kras-G12d In Pancan: Protein Centered Pharmacophore Htvs Approach., Anupam Dhasmana, Swati Dhasmana, Sudhir Kotnala, Vivek Kumar Kashyap, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chuahan

Research Symposium

Background: As per key statistics of American Cancer Society 2021, Pancreatic Cancer (PanCan) affects around 60,430 persons a year in the U.S. and is tricky to diagnose & treat. Studies revealed that African Americans have a 50–90% higher incidence of PanCan compared to other ethnic groups. Oncogenic KRAS mutation is the signature genetic incident in the progression and development of PDAC. KRAS is the most common protein which is 95% times mutated in PDAC condition. By considering this alarming situation our group is now focused on to develop therapeutic portfolio against KRAS-G12D mutation associated PanCan by using high through-put virtual …

Cell-Based Experimental Evidence To The Anti-Covid-19 Potential Of Ashwagandha And Honeybee Propolis Ingredients, Renu Wadhwa, Durai Sundar, Yoshiyuki Ishida, Keiji Terao, Sunil C. Kaul

Research Symposium

Background: The COVID-19 pandemic emerged in December 2019 by a novel strain of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has led to new endeavours in repurposing of existing drugs, anti-COVID-19 vaccine and drug development. Natural products, due to their general safety and wider availability, have attracted research and public attention. In this study, we report anti-COVID potential of compounds from honeybee propolis and Ayurvedic herb, Ashwagandha. Effect of active ingredients was studied on human cell surface receptors (ACE-2:Angiotensin Converting Enzyme-2/Spike protein and TMPRSS2:Transmembrane Protease Serine 2), critical for virus infection and virus main protease (Mpro, essential for virus replication), …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …

Pro-Apoptosis Activity Of Pogostemon Cablin Benth. Against Nasopharyngeal Carcinoma Through The Bcl-2 Inhibition Signaling Pathway: A Computational Investigation, Aigia Syahraini, Essy Harnelly, Feri Eko Hermanto

Makara Journal of Science

Resistance to chemotherapy and radiotherapy frequently emerges in the later stage of nasopharyngeal carcinoma (NPC) tumorigenesis. The decreased response of NPC to radiotherapy and chemotherapy occurs owing to the inhibition of cancer cell apoptosis by the B-cell lymphoma-2 (BCL-2) protein. Thus, inhibiting BCL-2 protein may become a powerful approach to eliminate NPC through apoptosis regulation. Meanwhile, Pogostemon cablin is reported to exhibit anticancer properties, but there are limited studies on its use for NPC treatment. The objective of this study is to investigate the potential bioactive compounds in P. cablin as anti-apoptosis BCL-2 protein inhibitors using in-silico approach. Natural compounds …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Drug Repurposing Using Gene Expression Data Mining, Yue Qiu

Dissertations, Theses, and Capstone Projects

The conventional drug discovery process that employs the "one disease, one target, one drug'' paradigm is expensive, time-consuming, and has a high rate of failure for multi-genic complex diseases. An alternative approach to drug discovery is to repurpose an existing drug that has been used to treat some medical conditions. Drug repurposing is considered a promising method due to its accelerated the process of drug discovery and lower overall cost and risk.

Drug-perturbed gene expression profiles are powerful phenotype readouts of biological systems, and they have been widely used in drug repurposing studies. However, the existing drug-perturbed gene expression datasets …

State-Of-The-Art Approaches For Sequencing, Assembling And Annotating Naphthenic Acid Degrading Bacterial Metagenomes, Henry H. Say

Electronic Thesis and Dissertation Repository

Naphthenic acids (NAs) are the main toxic component of oil refinery wastewater and require special processes to be removed. Harnessing bacterial biodegradation for NA removal has the potential to be effective, yet NA-degrading bacteria and pathways are poorly understood and uncharacterized. To improve our understanding of NA degradation, I characterize the metagenomes of novel NA-degrading bacterial communities seeded in NA-enriched granulated activated carbon (GAC) filters. I demonstrate methods that maximize the throughput of extraction, sequencing, and annotation of novel metagenomes - producing 72 MAGs and other 5432 circular contigs - 226 of which were putative phages. I also include state-of-the-art …

Generative Ai-Assisted Pathway Analysis And Interpretation Of Rna-Seq Experiment Data, Junguk Hur

AI Assignment Library

No abstract provided.

Predicting Marine Teleost Responses To Ocean Warming And Pollution, Akila Harishchandra

Electronic Theses and Dissertations

Ocean warming and pollution are two detrimental anthropogenic factors causing rapid marine ecosystem degradation recorded in the past decades. These factors alter the marine environment intolerable for many marine species, forcing them to either adapt or shift their contemporary habitat ranges to reduce the extinction risk embedded with environmental degradation. Estimating marine species’ habitat range shifts, and their potential for developing adaptive mechanisms are critical for ecosystem conservation and management, human health risk assessment, and climate change vulnerability assessments. Given that, for the first chapter of this thesis, we focused on developing a species distribution model (SDM) integrating marine species …

Evolution Of Overlapping Reading Frames In Virus Genomes, Laura Muñoz Baena

Electronic Thesis and Dissertation Repository

Viruses are formidable pathogens that represent the majority of biological entities in our planet, and their genomes are a source of interesting enigmas. One feature in which virus genomes are usually rich, is the presence of overlapping reading frames (OvRFs) — portions of the genome where the same nucleotide sequence encodes more than one protein. OvRFs are hypothesized to be used by viruses to encode proteins more compactly and to regulate transcription. In addition, OvRFs might be a source of gene novelty, facilitating the creation of new open reading frames (ORF) within the transcriptional context of existing ones.

To characterize …

Mutation-Induced Changes In The Stability, B-Cell Epitope, And Antigenicity Of The Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud, Nira Meirita Wijayanti, Muhammad Hermawan Widyananda, Lailil Muflikhah, Nashi Widodo

Karbala International Journal of Modern Science

The spike (S) protein is a major antigenicity site that targets neutralizing antibodies and drugs. The growing number of S protein mutations has become a severe problem for developing effective vaccines. Here, we investigated four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that were the most infectious and widespread during the COVID-19 pandemic to determine the trends and patterns of mutation-induced changes in the stability, B-cell epitope, and antigenicity of the SARS-CoV-2 S protein. The data showed that the Beta and Gamma variants had three mutations on the receptor-binding domain (RBD), which is the specific site on the S …

Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen

Dartmouth College Ph.D Dissertations

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …

Examining The Different Soil Horizons Of White Oak Mountain, Tn And Their Effect On The Soil Microbial Community, Ji Won Moon, Timothy D. Trott

Research in Biology

Soil microorganisms participate in the diverse interaction within virtually all ecosystems, consequently affecting the associated human and animal population. Identifying how edaphic variables alter the functional and taxonomic diversity of the soil microbial community requires an examination of total microbial soil diversity and abundance. This research study examined the effect of soil depth and horizon on the soil microbial community composition of White Oak Mountain. The soil microbial community was characterized by 16S/18S/ITS rDNA amplicon sequencing of the DNA extract of six samples from the three major soil types identified: HcE, MoE, and uMvC. OTU clustering analysis and both alpha …

The Impact Of Soil Disturbance On Soil Bacterial Community Composition, Marie A. Rodriguez, Mark Peach, Timothy D. Trott

Research in Biology

Soil bacterial communities are an important part of terrestrial ecosystems due to their roles in biogeochemical cycling processes. Consequently, understanding how soil disturbance affects the soil bacterial diversity is vital to understanding the entire ecosystem. In this study we examined the effects of soil disturbance (by mining) on the soil bacterial community composition from three sites on Bauxite Ridge in Southeast Tennessee compared to three undisturbed sites in a nearby location. The soil bacterial community was analyzed by 16S rDNA amplicon sequencing of total DNA extracted from the soil samples collected from each of the six sites. Characterization of the …

Growth Of Purple Sulfur Bacteria Allochromatium Vinosum On Solid Phase Metal Sulfides As Sulfur And Electron Sources, Hugo Alarcon

Open Access Theses & Dissertations

Purple sulfur bacteria (PSB) are photosynthetic microorganisms known for their vital roles in geochemical cycles, especially the sulfur cycle, within anoxic photic environments. PSB are also key contributors to the nitrogen, carbon, and oxygen cycles. This study focuses on the autotrophic growth of Allochromatium vinosum, a model strain of PSB, that utilize solid-phase metal sulfides (MS) as both sulfur and electron donors. Through characterizing the growth profiles of A. vinosum on pyrite (FeS2), nickel sulfide (NiS), and iron monosulfide (FeS) nanoparticles, respectively, and investigating the bacteria-MS interaction mechanisms, this work expands our current knowledge of the metabolic capabilities and flexibility …

Merging Clinical And Genomic Data In Patients With Acute Leukemia For Downstream Analysis, Amanda Bataycan

Open Access Theses & Dissertations

The purpose of this study is to integrate multiple sources of information from patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) to construct organized datasets that would enable downstream bioinformatics and statistical analyses of the patientsâ?? survival status and overall survival times in relation to their demographic, clinical, and genomic mutation profiles. With NIH Genomic Data Commons as the primary data resource and cBioPortal as the access portal, datasets on 149 and 603 unique patients with AML and ALL, respectively, were obtained. Python scripts were written to compile individual patientsâ?? single nucleotide variant (SNV) data files into …

Modeling The Egyptian Goose (Alopochen Aegyptiaca) Invasion; And Future Concerns, Percival Matzinger Marshall

Graduate Theses and Dissertations

In an increasingly interconnected world, the ecological and financial cost of invasive species is expected to continue to climb through the movement of exotic biota. Understanding the driving forces behind how a species invades, what environments promote their establishment, and what impacts they are likely to have on the invaded environment are all critical for management. Waterfowl, order Anseriformes, are one such category of invasive species of concern due to their popularity of accidental introduction, ease of movement, and propensity to affect both terrestrial and aquatic ecosystems. The Egyptian Goose (Alopochen aegyptiaca) is a native to the African continent that …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston

Electronic Theses and Dissertations

Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …

Sequestered Sequences: A Bioinformatic Approach To The Forgotten Genome, Dylan Barth

UNLV Theses, Dissertations, Professional Papers, and Capstones

As high throughput sequencing generates ever increasing amounts of genetic and epigenetic data new lines of inquiry open up in the field of genomic research. In this thesis, we discuss three ways in which we can utilize public databases of next generation genomic data in order to study areas of the genome previously ignored by traditional approaches. These include the study of linker regions between domains of proteins, indirect enhancers that do not strongly contact promoters of genes they regulate, and transposon-derived enhancer elements. The work uncovers many exceptions to known biological principles, and adds nuance to our understanding of …

Visual Complexity Of The Time-Frequency Image Pinpoints The Epileptogenic Zone: An Unsupervised Deep-Learning Tool To Analyze Interictal Intracranial Eeg, Sarvagya Gupta

Graduate Masters Theses

Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, continues to pose significant challenges in diagnosis and treatment, particularly among children. Despite substantial advancements in medical technology and treatment modalities, localization of the part of brain that causes seizures (Epileptogenic Zone) remains a difficult task. Intracranial EEG (iEEG) is often used to estimate the epileptogenic zone (EZ) in children with drugresistant epilepsy (DRE) and target it during surgery. Conventionally, iEEG signals are inspected in the time domain by human experts aiming to locate epileptiform activity.

Visual scrutiny of the iEEG time-frequency (TF) images can be an alternative way to review …