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Full-Text Articles in Molecular Biology

The Role Of Uchl1 In Skeletal Muscle Development And Regeneration, Ryan Antony Jan 2024

The Role Of Uchl1 In Skeletal Muscle Development And Regeneration, Ryan Antony

Dissertations and Theses

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally discovered in neurons. UCHL1 is also expressed in skeletal muscle, but its functions remain to be fully understood. Myogenesis is a critical process involved in embryonic development, growth, and regeneration following injury. Skeletal muscle injury is prevalent in trauma and surgical procedures, and skeletal muscle ischemia-reperfusion (IR) injury is a common yet dangerous public health problem. Here we reported that UCHL1 negatively affects muscle growth during aging as well as the regeneration process following IR injury. First, we observed that UCHL1 knockdown in C2C12 myoblasts resulted in increased …


Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw May 2023

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …


Essential Amino Acid (Eaa) Regulation Of Skeletal Muscle Protein Turnover With Age, Mary Komp May 2022

Essential Amino Acid (Eaa) Regulation Of Skeletal Muscle Protein Turnover With Age, Mary Komp

Graduate Theses and Dissertations

Skeletal muscle (SM) is vital for both long term health and quality of life. Recent research suggests an increase in catabolic signals with age triggers pathologic conditions, such as sarcopenia. Although results from in vitro studies model how EAA can regulate muscle protein synthesis (MPS), the relevance of these models to muscle protein breakdown (MPB) and the presence of physiological EAA concentrations remains to be established. Therefore, the objective of this study was to determine the effects of a low, normal, and supra physiological dose of EAA (0.2, 1.0, and 3.0 x EAA) in a young (passages 2-10) and aging …


A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso Jul 2021

A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso

Graduate Theses and Dissertations

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It …


Structural Characterization Of The Novel Flightin Domain Wyr And Its Defining Role In The Thick Filament Structure And Mechanics, Lynda Menard Jan 2021

Structural Characterization Of The Novel Flightin Domain Wyr And Its Defining Role In The Thick Filament Structure And Mechanics, Lynda Menard

Graduate College Dissertations and Theses

The evolutionary success of Insecta has been attributed largely to the development of efficient means of motility: flight powered by muscle architecture harboring a largely conserved yet tunable system of power relay. The indirect flight muscle (IFM) of Drosophila melanogaster is a well-studied model for dissection of the structural and mechanical means by which muscle operates and evolves. Striated muscle, conserved throughout Animalia, is demarcated by an ordered array of thick- and thin-filaments prominently composed of the proteins myosin and actin. Flightin (fln) is a myosin binding thick filament protein essential for IFM stability, structure and function. The manner by …


Simulation Of A Rat Muscle-Tendon Unit With Hill-Type Model Dynamics And The Study Of Viscoelasticity In A Collagen Molecule Via Molecular Dynamics, Veronica Siko Jan 2021

Simulation Of A Rat Muscle-Tendon Unit With Hill-Type Model Dynamics And The Study Of Viscoelasticity In A Collagen Molecule Via Molecular Dynamics, Veronica Siko

West Chester University Master’s Theses

The field of biological science has established that tendons transfer muscular forces to adjacent bones, but there is a dearth of information about the underlying physical principles of these interactions and how the property of viscoelasticity (displayed in tendons as a difference in mechanical response to stress with differing stretching rates) is encompassed in the collagen of tendons. This thesis details the results of concentric and eccentric contractions of the rat muscle-tendon unit (MTU) with and without viscoelasticity (concentric contraction requires active shortening of the muscle, while eccentric contraction requires active lengthening of the muscle) (Lovering & Brooks, 2014). Once …


The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer Aug 2019

The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …


Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon Dec 2017

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations & Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …