Cellular and Molecular Physiology Commons^™

Threshold Concentration And Random Collision Determine The Growth Of The Huntingtin Inclusion From A Stable Core, Sen Pei, Theresa C. Swayne, Jeffrey F. Morris, Lesley Emtage

Publications and Research

The processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases but poorly characterized in living cells. In S. cerevisiae, inclusions formed by mutant huntingtin (mHtt) have some characteristics of biomolecular condensates but the physical nature and growth mechanisms of inclusion bodies remain unclear. We have probed the relationship between concentration and inclusion growth in vivo and find that growth of mHtt inclusions in living cells is triggered at a cytoplasmic threshold concentration, while reduction in cytoplasmic mHtt causes inclusions to shrink. The growth rate is consistent with incorporation of new material through collision and coalescence. …

Identifying The Molecular Pathways That Drive Retinal Degeneration In The Childhood Neurodegenerative Disease: Mucolipidosis Type Iv, Michael Pamonag

Masters Theses, 2020-current

Humans, like many other vertebrates, possess five Aristotelian senses (vision, olfaction, hearing, taste, and touch) which we use to experience and navigate our environment. Our visual system is the only source of light detection and light signaling in our bodies. This makes our visual system essential for detecting movement, distance, time of day, and seasonal changes in the length of days within our environment. The visual systems of most animals are designed to capture photons of visible light and convert that energy into a neurological signal (visual signal) to be transmitted to brain regions responsible for visual perception1 . This …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations and Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …

The Effect Of Fluid Flow Shear Stress And Substrate Stiffness On Yes-Associated Protein (Yap) Activity And Osteogenesis In Murine Osteosarcoma Cells, Thomas R. Coughlin, Ali Sana, Kevin Voss, Abhilash Gadi, Upal Basu-Roy, Caroline M. Curtin, Alka Mansukhani, Oran D. Kennedy

Publications and Research

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/ physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Establishing And Validating Methods To Assess The Influence Of Exercise On Circulating Exosome Profiles In Sedentary Older Adults, Heather Quiriarte

LSU Master's Theses

Aging is associated with progressing cellular structural and functional changes, and sedentary behavior can exacerbate these hallmarks of aging. Routine exercise is known to have beneficial effects on physiological systems, but the exact molecular mechanisms behind the health benefits are unclear. Emerging evidence suggests extracellular vesicles called exosomes are involved in the intercommunication between cells and organs following exercise by delivering their cargo such as proteins and miRNAs. miRNA profiles in older adults following acute and chronic exercise need further exploration. Specifically, the effects of regular low-intensity physical activity (LPA) breaks in sedentary time on proteins and miRNA packaged in …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Cold-Induced Metabolic Changes In Lean, Nag-1 Transgenic Mice, Rachel J. Davey

All Master's Theses

Obesity is a multifaceted metabolic disorder with severe worldwide public health consequences. While obesity can often be treated using diet and exercise, there are complex genetic interactions driving obesity that don’t always respond to such changes. One important research focus for addressing genetic factors is activating brown adipose tissue which increases thermogenesis, the process of burning stored fats to generate heat. Cold exposure is a known way to activate brown adipose tissue through b3-adrenergic signaling. This signaling pathway causes an upregulation of thermogenesis in brown adipocytes and beige adipocytes, which is white adipose tissue that “browns” and becomes metabolically active. …

Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression In Target Human Retinal Progenitor Cells, Jing Zhou, Miguel Flores‑Bellver, Jianbo Pan, Alberto Benito‑Martin, Cui Shi, Onyekwere Onwumere, Jason Mighty, Jiang Qian, Xiufeng Zhong, Tasmim Hogue, Baffour Amponsah‑Antwi, Linda Einbond, Rajendra Gharbaran, Hao Wu, Bo‑Juen Chen, Zhiliang Zheng, Tatyana Tchaikovskaya, Xusheng Zhang, Hector Peinado, Maria Valeria Canto‑Soler, Stephen Redenti

Publications and Research

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell‑to‑cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three‑dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC‑derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo‑predicted targetome correlates with Gene Ontology (GO) pathways involved in …

A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti

Seton Hall University Dissertations and Theses (ETDs)

Multiple myeloma (MM) is a hematologic cancer caused by a mature B cell neoplasm, or plasmacytoma, that infiltrates the skeleton at several sites. The disease is characterized by uninhibited transformed plasma cell proliferation that disrupts skeletal homeostasis leading to decreased bone modeling and increased bone resorption. Osteolytic lesions (OL) or voids left in the bone, remain long after the treatment of the cancer and indicate disease progression to myeloma bone disease (MBD). Current combinatorial MM therapies inhibit malignant plasma cell proliferation, slow the progression towards MBD, and increase the mean five-year survival rate, but do little to improve osteoblastic function …

Expression And Localization Of The 14-3-3 (Ywha) Protein Family Within Mammals, Neha Kumrah, Santanu De

Mako: NSU Undergraduate Student Journal

The 14-3-3 (YWHA) are a family of homologous, acidic, and highly conserved proteins expressed abundantly and ubiquitously in a wide array of organisms ranging from plants to animals, including humans, which regulate important cellular events. Within mammals, seven isoforms of 14-3-3 exist: β, γ, ε, ζ, η, τ, and σ (stratifin), each of which is encoded by a unique gene. Studies have shown similar expression patterns among mammalian species. The 14-3-3 proteins are commonly expressed and have proven to play critical roles in proper cellular localization, function, and homeostatic regulation. Numerous researchers have investigated the expression and localization patterns of …

Phenotypic Plasticity Of Japanese Medaka Gill In Response To Changing Salinities, Laura V. Ellis

Graduate Theses and Dissertations

Japanese medaka (Oryzais latipes) are euryhaline fish, meaning they are capable of surviving in a variety of salinities from fresh water to seawater. The ability to maintain an internal osmotic concentration stems from the phenotypic plasticity of the osmoregulatory organs, the gill, kidney, intestine, and integument. The gill is the main site of osmotic and ionic regulation in fish due to the three-dimensional structure, the direct contact with the outside environment, and the composition of the gill cells. Fish gills are multifunctional as they regulate water movement, acid/base exchange, nitrogenous waste excretion, and ion fluctuations. In freshwater environments, fish are …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Kinetics Of Notch Signaling During Osteoclastogenesis, Amber Larissa Framstad

EWU Masters Thesis Collection

Bone remodeling, the process of removing and replacing damaged bone matrix, is a dynamic physiological process essential to maintaining bone composition and integrity. Improper coordination of resorption and formation can lead to pathologic changes in bone composition and quality, as is seen in osteoporosis, a bone disorder most seen in post-metapausal women attributed to decreased estrogen levels. The Notch signal pathway is a highly conserved direct cell communication pathway known to regulate cell proliferation, differentiation and survival in many cell types including the differentiation of osteoclasts from bone marrow macrophages (BMMs). Osteoclastogenesis is initiated in BMMs by receptor activator of …

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …

Combinatorial Discovery And Validation Of Heptapeptides With Utp Binding Induced Structure, Daniela Kroiss, James Aramini, Sangitaa Ragoonath, Rein V. Ulijn, Tell Tuttle

Advanced Science Research Center

In biology, supramolecular recognition typically involves an ‘induced-fit’ mechanism, where structures rearrange upon complexation to accommodate binding ligands. Designing minimalistic compounds with such adaptability is challenging as they involve subtle conformational changes that are energetically similar. Here, we demonstrate the integration of combinatorial screening with molecular modelling to identify heptapeptides that form a stable loop upon recognition of uridine triphosphate (UTP). Peptide sequences selected using phage display were refined computationally and correlated with experimental KD values. This combined approach may serve as a method for the de novo selection and subsequent rationalization of the compositional and organizational principles that dictate …

Neurodegenerative Modeling: Tau Protein, Degradative Pathways, And Gene Expression Profiling Of Human Ipsc-Derived Neural Precursors And Differentiated 3-D Neural Sphere Versus 2-D Monolayer Cultures, Kyle H. Anthoney

Cal Poly Humboldt theses and projects

Human induced pluripotent stem cells offer a model for human brain development and disease by differentiation into brain organoids; however, current neural culture systems lack the microenvironment, neuronal circuits and connectivity, vascular circulation, and immune system that exist in vivo. After differentiation and development of neuronal and non-neuronal cell types within two formats of cell cultures, we can visualize and recapitulate in vivo protein accumulation, gene expression, and degradative processes such as autophagy. Using RNA extraction, purification methods and reverse transcription I compared traditional monolayer cultures and novel 3-D neural sphere cultures via gene expression analysis. This analysis indicated …

Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin

Publications and Research

The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …

Histology Atlas: Basic Mammalian Tissue Types (Biol 105), Joshua Barnes, Daniel J. Yakubov, Corinna Singleman, Nathalia G. Holtzman

Open Educational Resources

This book is a guide to the basic histology lab conducted as a part of the Queens College, CUNY Biology Department Bio105 General Biology: Physiology and Cell Biology course. This course is the first half our two-part series for biology majors. The actives are designed to be conducted over a single 3-hour lab periods which focus on the relationship of form and function of the cellular and organ level anatomy and physiology. Step by step instructions for each slide set are provided for all the key organs.

In addition to the full text of the book, we also provide a …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Human Anatomy And Physiology I: Course Map With Expected Learning Outcomes, Carlos Liachovitzky

Open Educational Resources

This document contains a list with all the Anatomy and Physiology I expected learning outcomes organized by topics, and grouped into ten units: 1. Introduction to A&P: body plan & organization; 2. Introduction to A&P: homeostasis; 3. The chemical level of organization; 4. Levels of organization: the cellular level of organization; 5. Levels of organization: the tissue level of organization; 6. Support and movement: integumentary system; 7. Support and movement: skeletal system & articulations; 8. Support and movement: muscular system; 9. Regulation, integration, and control: nervous system; 10. Regulation, integration, and control: special senses

Each learning outcome is referred to …