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Full-Text Articles in Life Sciences

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov Nov 2023

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 Nov 2023

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 Nov 2023

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 Aug 2023

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 Apr 2023

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 Apr 2023

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 Apr 2023

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 …