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Articles 1 - 30 of 45
Full-Text Articles in Life Sciences
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Doctoral Dissertations
Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …
Chemical Modification And Evaluation Of Cells Towards Use As Delivery Tools, Bishnu Prasad Joshi
Chemical Modification And Evaluation Of Cells Towards Use As Delivery Tools, Bishnu Prasad Joshi
Doctoral Dissertations
CHEMICAL MODIFICATION AND EVALUATION OF CELLS TOWARDS USE AS DELIVERY TOOLS SEPTEMBER 2023 BISHNU PRASAD JOSHI M.S., SRI SATHYA SAI INSTITUTE OF HIGHER LEARNING Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Michelle E. Farkas Endogenous cells are being studied for use in various applications, such as next generation therapeutics and drug delivery vehicles. This is on account of their biocompatibility, amenable distribution profiles, and in many instances, recruitment to and localization of diseased tissues. Multiple cell types have been employed, including macrophages, stem cells, red blood cells, and T cells. Most examples of cell-based delivery utilize phagocytosed entities as …
Head Stabilization And Cortical Activation In Contact Sport Athletes During Walking Under Different Visual Task Constraints, Sam Zeff
Doctoral Dissertations
Contact sport participation exposes athletes to repetitive sub-concussive head impacts, which have been shown to elicit cortical neurophysiologic, cognitive, and motor performance alterations that have the potential to disrupt visual perception. Despite the growing concern regarding sub-concussive impacts, our understanding of their implications on motor performance and risk for further injury is limited. A stable head provides a consistent perceptual platform for the visual and vestibular sensory systems, but the effects of contact sport participation on head stability and visual perception remain poorly understood. The goal of this dissertation was to understand whether contact sport participation modifies athletes’ ability to …
Role Of Fat Content On The Structure And Function Of Human Skeletal Muscle, Joseph A. Gordon Iii
Role Of Fat Content On The Structure And Function Of Human Skeletal Muscle, Joseph A. Gordon Iii
Doctoral Dissertations
Muscle size does not fully explain variations in muscle strength. Fat content has been implicated in muscle weakness, though this relationship remains unclear. The relationship between fat and strength may vary between scales (e.g., cellular, organ, and organism). The goal of this dissertation was to clarify the role of fat in the structure and function of muscle using in vitro and in vivo techniques across multiple scales in adults 21-45 years old. Study 1 tested the agreement of intramyocellular lipid (IMCL) content between oil red o (ORO) and magnetic resonance spectroscopy (MRS) techniques. These measures of IMCL were also compared …
Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage
Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage
Doctoral Dissertations
RNA is poised to revolutionize medicine. By simply changing the sequence, one therapeutic can be converted into a wholly new one, with little or no change in manufacturing and formulation. While a single mRNA vaccine produced at massive scale can treat billions, the re-codability of RNA will also enable the widespread growth of personalized medicines. T7 RNA polymerase is highly efficient at the synthesis of therapeutic RNA, but is known to produce unintended RNA impurities during synthesis. These products arise from the encoded RNA rebinding the enzyme such that its 3’ end serves as a primer for extension. This leads …
Bifidobacterial Metabolism Of Fucosylated Human Milk Oligosaccharides Influences Structure And Function Of The Infant Gut Microbiome, Liv R. Dedon
Doctoral Dissertations
Human milk contains human milk oligosaccharides (HMOs) that are indigestible and pass intact through the infant gastrointestinal tract where they are available for microbial metabolism. HMOs incorporate the same monosaccharide building blocks but vary structurally in primary sequence of monomeric components. Primary sequences are further diversified by degree of polymerization, branching, and secondary modifications such as fucosylation. Fucosylated HMOs (fHMOs) are highly abundant and can account for over 30% of total HMOs. Infant-colonizing Bifidobacterium longum subsp. infantis (B. infantis) possesses a specialized gene cluster conveying the ability to metabolize fHMOs. This study presents an in-depth analysis of B. …
Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker
Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker
Doctoral Dissertations
Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Doctoral Dissertations
The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …
Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan
Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan
Doctoral Dissertations
Biomaterials are widely applied for the diagnosis and treatment of numerous diseases. In addition to fulfilling specific biological functions, biomaterials must also be non-toxic, biocompatible, and sterilizable to be regarded as safe-for-use. Polymers are excellent candidates for fabricating functional biomaterials due to their wide availability and varied properties and may be natural or synthetic. Polymer precursors are fabricated into coatings, foams, scaffolds, gels, composites, and nanomaterials for several biomedical applications. This dissertation focuses on two types of polymeric biomaterials – protein-based materials and synthetic polymeric nanoparticles. Proteins are biopolymers that naturally occur with a variety of structural and functional properties. …
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Doctoral Dissertations
Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …
Quality Of Life For Women With Chronic Lyme Disease: A Socioeconomic Investigation, Dale M. Jones
Quality Of Life For Women With Chronic Lyme Disease: A Socioeconomic Investigation, Dale M. Jones
Doctoral Dissertations
This is a mixed methods investigation of how chronic Lyme disease, including Lyme-like diseases and co-infections, affects the quality of life of women who have chronic Lyme. Both quantitative and qualitative methods were used during three phases of research: a 91-question survey instrument followed by focus group discussions and written narratives. The research considered the socioeconomic impact on quality of life in five areas: obtaining a diagnosis, relationships and personal support systems, struggles with the medical system, the ability to work, and access to treatment. There were 500 responses to the survey, of which 373 were analyzed; 11 participants in …
Deciphering Protein Higher-Order Structure And Interactions Via Diethylpyrocarbonate Labeling-Mass Spectrometry, Xiao Pan
Doctoral Dissertations
The study of protein higher-order structures is vital because it is closely related to the investigation of protein folding, aggregation, interaction and protein therapeutics. Consequently, numerous biochemical and biophysical tools have been developed to study protein higher-order structures in many different situations. The combination of covalent labeling (CL) and mass spectrometry (MS) has emerged as a powerful tool for studying protein structures and offers many advantages over other traditional techniques, such as better structural coverage, high throughput, high sensitivity, and the ability to study proteins in mixtures. This dissertation focuses on diethylpyrocarbonate (DEPC) as an effective CL reagent that can …
Oxybenzone And The Mammary Gland: Impact Of An Environmental Pollutant On Health, Disease & Ethical Decision-Making, Klara Matouskova
Oxybenzone And The Mammary Gland: Impact Of An Environmental Pollutant On Health, Disease & Ethical Decision-Making, Klara Matouskova
Doctoral Dissertations
The environmental pollutant and common sunscreen compound oxybenzone is a benzophenone type UV light chemical filter used in industrial and consumer goods. This chemical widely contaminates human tissues, non-human species, and environmental matrices. In this dissertation, oxybenzone is investigated for its effects on the mouse mammary gland in the offspring following perinatal exposure; after perinatal and prepubertal exposures as a dual environmental insult during two sensitive times of development; and in adults after exposure during pregnancy & lactation as an environmental factor potentially increasing the tissue susceptibility to mammary tumors. Chapter 1 introduces the mammary gland. Chapter 2 reviews UV …
Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy
Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy
Doctoral Dissertations
The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …
Interactions Between Titanium Dioxide Nanoparticles (Nps) And Mucin, . Boimin
Interactions Between Titanium Dioxide Nanoparticles (Nps) And Mucin, . Boimin
Doctoral Dissertations
Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many food, consumer, and industrial products. However, little is known about the overall effects of TiO2 NPs on the environment or human health. In order to elucidate the fate, transformation, transport, and toxicological impact of TiO2 NPs, a better understanding is needed of how the physicochemical properties of TiO2 NPs (e.g. size, charge, curvature, hydrophobicity, and surface functionality) interact with their microenvironments (e.g. pH, temperature, bile acids, microbiome, enzymes, surface-active components, and biopolymers). Living organisms including humans have a natural mechanism to protect themselves from physical, biological, …
Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi
Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi
Doctoral Dissertations
The glutathione (GSH) system evolved to combat oxygen toxicity in nearly all living organisms, and serves as the predominant cellular redox buffer in vertebrates. This dissertation explores the roles of GSH during embryogenesis using the zebrafish (Danio rerio). The first agnostic in vivo characterization of GSH utilization in the embryo revealed strict spatiotemporal GSH profiles in developing organ systems. Interruption of these GSH profiles by exogenous xenobiotics led to organ specific adverse developmental outcomes; pancreatic β-cells were found to be especially susceptible and developed atypical morphologies following redox active xenobiotic exposures. Pancreatic β-cells lacked expression of Nrf2a (Nuclear …
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Doctoral Dissertations
Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …
Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das
Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das
Doctoral Dissertations
Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …
Cytochrome P450 Monooxygenase-Mediated Lipid Metabolism In Obesity And Colon Tumorigenesis, Weicang Wang
Cytochrome P450 Monooxygenase-Mediated Lipid Metabolism In Obesity And Colon Tumorigenesis, Weicang Wang
Doctoral Dissertations
Colon cancer is a major public health issue: it is expected to have 140,250 new cases and 50,630 deaths during 2018, making colon cancer the third most common type of cancer and the second leading cause of cancer death in the United States. Obesity is associated with enhanced colonic inflammation, which is a major risk factor of colorectal cancer. Currently, more than 35% of adults and nearly 17% of children are obese. Considering the obesity and colon cancer epidemic in the United States, there is an urgent need to identify novel therapeutic targets for obesity and colon cancer. Here, using …
Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao
Doctoral Dissertations
Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pKa on host-guest interactions …
Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta
Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta
Doctoral Dissertations
Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. The “superbug” risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that are highly resistant to available treatments. Synthetic macromolecules such as polymers and nanoparticles have emerged as promising antimicrobials. Moreover, ability to modulate nanomaterial interaction with bacterial cellular systems plays a pivotal role in improving the efficacy of the strategy. In the initial studies on engineering nanoparticle surface chemistry, I investigated the role played by surface ligands in determining the antimicrobial activity of the nanoparticles. In further study, …
Improving Chinese Mothers’ Health Literacy: A Wechat Intervention, Qiong Chen
Improving Chinese Mothers’ Health Literacy: A Wechat Intervention, Qiong Chen
Doctoral Dissertations
The health literacy and eHealth literacy of women during the reproductive age is crucial, as it can affect their health and the health of their children. Promoting health literacy is essential to achieve mothers’ empowerment by improving access to and capacity of using health information effectively. However, functional, interactive, and critical health literacy and eHealth literacy have never been assessed among Chinese women. The first study during this dissertation assessed functional, interactive, and critical health literacy and eHealth literacy among 421 of Chinese mothers with children under 3 years old. The results revealed overall less than optimal level of health …
Multi-Level Barriers To Art Adherence Among Hiv-Infected Women In Rural Eswatini: A Mixed Methods Approach, Nozipho Becker
Multi-Level Barriers To Art Adherence Among Hiv-Infected Women In Rural Eswatini: A Mixed Methods Approach, Nozipho Becker
Doctoral Dissertations
Eswatini has the highest global prevalence of HIV despite universal access to free treatment. Lack of compliance continues to be a significant challenge for HIV care and management programs throughout the country. Studies investigating barriers to antiretroviral therapy (ART) adherence, particularly in women, who are the most vulnerable to HIV infections, are limited. The disproportionate impact of HIV on women can be attributed to multiple risk factors at the individual, household, and community/structural levels. Women living in rural settings are particularly at risk as a result of socio-cultural and environmental vulnerabilities such as oppressive traditional practices, intimate partner violence, and …
Game-Assisted Rehabilitation For Post-Stroke Survivors, Hee-Tae Jung
Game-Assisted Rehabilitation For Post-Stroke Survivors, Hee-Tae Jung
Doctoral Dissertations
Stroke is a leading cause of permanent impairments among its survivors. Although patients need to go through intensive, longitudinal rehabilitation to regain function before the stroke, patients show poor engagement and adherence to rehabilitation therapies which hampers their recovery. As a means to enhance stroke survivors' motivation, engagement, and adherence to intensive and longitudinal rehabilitation, the use of games in stroke rehabilitation has received attention from research and clinical communities. In order to realize this, it is important to take a holistic, end-to-end research approach that encompasses 1) the development of game technologies that are not only entertaining but also …
Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis
Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis
Doctoral Dissertations
Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability …
Changes In Muscle Control And Coordination In Novel Task Learning, Sangsoo Park
Changes In Muscle Control And Coordination In Novel Task Learning, Sangsoo Park
Doctoral Dissertations
Learning many daily life motor skills is critical for survival and the quality of living in humans. As children, we develop walking and running patterns to move the body from point A to B without falling, and we learn to grasp a wide variety of objects during activities of daily living. Motor skills can be properly performed by appropriate muscle activations which are controlled by the central nervous system. How does the central nervous system develop and fine-tune its control strategy to learn a new motor skill? The aim of this dissertation was to better understand how human participants alter …
Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria
Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria
Doctoral Dissertations
Liver is the largest internal organ of the human body. It performs a multitude of functions. Therefore, it is provided with a huge regenerative capacity however, because of the same reason it is also prone to various diseases. Hence, it is essential to understand liver development in order to understand liver regeneration and liver diseases to provide better therapeutic targets and solutions. Liver development is orchestrated by a variety of intrinsic and extrinsic factors. The major focus of this dissertation thesis is to elucidate the role of BMP signals and YY1/VEGFA regulated signals in liver development. Liver organogenesis initiates with …
Sleep, And Its Relation To Non-Motor Deficits In Patients With Cerebellar Ataxia, Akshata Sonni
Sleep, And Its Relation To Non-Motor Deficits In Patients With Cerebellar Ataxia, Akshata Sonni
Doctoral Dissertations
The cerebellum is a highly connected structure, and its involvement in sleep – which is a dynamic process that is modulated by a complex set of neural systems – can come about through a number of neural pathways. We conducted two studies aimed at furthering our understanding of cerebellar involvement in sleep behavior and physiology, as well as measuring the impact of poor sleep on mood and cognition in patients with cerebellar degeneration. First, by means of an online battery including measures of sleep and neuropsychiatric function, we collected data from 176 patients with cerebellar ataxia. We found strong evidence …
Robust Biosensors For Healthcare Applications: From High-Content Screening To Point-Of-Care Testing, Ngoc D. B. Le
Robust Biosensors For Healthcare Applications: From High-Content Screening To Point-Of-Care Testing, Ngoc D. B. Le
Doctoral Dissertations
Efficient detection of proteins, mammalian cells, microorganisms and other biological systems in complex mixture is essential in disease diagnosis and environmental health. Therefore, technological platforms that provide sensors of high sensitivity, selectivity and stability are greatly desired. Recently, the ‘chemical-nose’ sensing approach has proved to be an effective strategy for profiling bio-relevant targets in complex mixtures. Detecting analytes in complex mixture is a challenge that conventional specificity-based sensors are still trying to solve due to the requirement of prior knowledge of the analyte, which is unknown in many cases. This thesis focuses on how to develop simple and robust …
Colicins - A Sound Antimicrobial Approach For The Prevention Of Catheter-Associated Urinary Tract Infections, Sandra M. Roy
Colicins - A Sound Antimicrobial Approach For The Prevention Of Catheter-Associated Urinary Tract Infections, Sandra M. Roy
Doctoral Dissertations
The emergence and spread of antibiotic resistance has created one of the greatest challenges in fighting infectious disease. We address the rise of antibiotic-resistant pathogens by examining the evolutionary history of a class of resistance determinants, the SHV b-lactamases. We isolated the genes that encode the SHV beta-lactamases (blaSHV genes) from clinical settings and from an environment essentially devoid of antibiotic use. Our data suggests that, counter to current dogma, the use of antibiotics in the clinic is not creating these resistance genes; genes for antibiotic resistance already exist in nature and our use of antibiotics in clinical …