Digital Commons Network^™

Spatial And Temporal Organization Of The Genome: Current State And Future Aims Of The 4d Nucleome Project, Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor, Anders S Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong

Journal Articles

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to …

Water-Fat Magnetic Resonance Imaging For The Assessment Of Human Fetal Adipose Tissue, Stephanie A. Giza

Electronic Thesis and Dissertation Repository

Adipose tissue is crucial for providing heat and energy to infants, especially at transitions such as birth and therefore must begin developing in utero. This development may be altered due to an adverse uterine environment, increasing the risk of developing later-life metabolic diseases such as obesity. An early assessment of fetal adipose tissue development through lipid accumulation could be key to understanding metabolic programming and minimizing this risk.

Water-fat magnetic resonance imaging (MRI) can non-invasively measure the lipid concentration of tissues and can therefore monitor the development of adipose tissue via tissue lipid concentration. This work demonstrated the feasibility …

Prenatal Buprenorphine Exposure Reduces Expression Of Myelin Proteins In Neonatal Longs-Evans Rat, Christopher James Grahe

Theses, Dissertations and Capstones

In the USA and especially in WV, there has been a surge in the rise of opioid use disorder (OUD), and with it a rise in neonatal abstinence syndrome (NAS). What makes this rise in NAS so unfortunate is that the Medications for OUD (MOUD) do not prevent the development of NAS. Although the relationship between MOUD and NAS is still unclear, it is thought that buprenorphine, one of the main substances used to treat OUD in pregnant women, may feed into the development of NAS, which may affect mental and physiological development and cause other health problems. Via understanding …

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …

On The Roles Of Trait Anxiety And Toll Like Receptor 4 In Amphetamine Sensitization In Adolescent Male Rats, Corey A. Calhoun

Graduate Doctoral Dissertations

Mammalian adolescence can be a difficult transition from childhood to adulthood, where increases in impulsivity and novelty- and risk-seeking are combined with heightened affect and elevated sensitivity to stress. Indeed, during adolescence, first drug use patterns emerge and in the continental United States, increasing misuse of amphetamines has been observed in adolescent youth. Myriad neural mechanisms underlie this shift in adolescence, including the dynamic remodeling of the mesocorticolimbic (MCL) pathway. Repeated drug administration affects neuroimmune substrates within the MCL circuit including toll-like receptor 4 (TLR4)Advances in addiction neuroscience indicate that drugs of abuse activate neural TLR4 and implicate glial TLR4 …

The Effects Of Executive Function Between Anxiety And Math Achievement In Adolescents, Mckenzie Hall

UNLV Theses, Dissertations, Professional Papers, and Capstones

Anxiety in Children can develop into pervasive disorders in adulthood if not treated. Research shows dysfunctional Executive Function (EF) and anxiety are both shown to have a negative impact on math achievement in children and adolescents (Trezise & Reeve, 2018; Kalaycioglu, 2015; Owens, Stevenson, Hadwin & Norgate, 2012). Chung, Weyandt, and Swentosky (2014) found biological and neuropsychological support for EF as a unitary and multifaceted processor for regulating our emotional states as well as our daily procedures. Anderson’s (2002) model of Executive Control System (ECS) allows the factors of EF to be examined using a developmental approach towards EF processes. …

Family-Centered Psychosocial Care For Pediatric Oncology Patients, Jessica W. Casey

UNLV Theses, Dissertations, Professional Papers, and Capstones

Psychosocial conditions are prevalent in pediatric oncology patients (Kahalley et al., 2013). Family and social support are essential aspects of a patient's health care outcomes (Merck & McElfresh, 2019). Anxiety and depression are common in pediatric oncology patients due to trauma during treatment (Pao & Kazak, 2015). These patients also can have preexisting developmental or behavioral conditions before starting treatment. Treatment side effects can also cause cognitive and behavioral changes (Nixon, 2014b). Nurses should be knowledgeable and confident in their ability to care for patients' psychosocial health and development. The purpose of this Doctor of Nursing Practice (DNP) project is …

Suppression Of Pi3k Signaling Is Linked To Autophagy Activation And The Spatiotemporal Induction Of The Lens Organelle Free Zone, Rifah Gheyas, Ramon Ortega-Alvarez, Daniel Chauss, Marc Kantorow, A. Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The terminal steps of lens cell differentiation require elimination of all organelles to create a central Organelle Free Zone (OFZ) that is required for lens function of focusing images on the retina. Previous studies show that the spatiotemporal elimination of these organelles during development is autophagy-dependent. We now show that the inhibition of PI3K signaling in lens organ culture results in the premature induction of autophagy within 24 h, including a significant increase in LAMP1+ lysosomes, and the removal of lens organelles from the center of the lens. Specific inhibition of just the PI3K/Akt signaling axis was directly linked to …

The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren

All ETDs from UAB

The prevalence and tremendous impact of diabetes mellitus has made glucose regulation of the insulin-producing -cell and surrounding pancreatic islet of Langerhans a center of public and research interests alike. A comprehensive understanding of these hormone-producing cells begins with their developmental origins. What are the genetic cues and participants in the tightly orchestrated process of their formation? Investigating the earliest determinants of islet-cell fate not only allows us to deeply understand mature - and islet-cell function, but also produces a data-driven template for how these cells can be reproduced in future stem-cell based diabetes therapies. LIM transcriptional complexes are indispensable …

Multiple Approaches To Auditory Rhythm: Development Of Sustained Musical Beat And The Relation To Language, Development Of Rhythmic Categories Via Iterated Production, And A Meta-Analytic Study Of Neural Entrainment To Beat, Karli Marie Nave

UNLV Theses, Dissertations, Professional Papers, and Capstones

Rhythm is ubiquitous to human communication, coordination, and experience of music. In this dissertation, I address three empirical questions through three different methodologies, all of which contribute to the growing body of literature on human auditory rhythm processing. In Chapter 2, I present a registered report detailing the results of independent conceptual replications of Nozaradan, Peretz, Missal, & Mouraux (2011), all using the same vetted protocol. Listeners performed the same tasks as in Nozaradan et al. (2011), with the addition of behavioral measures of perception. In neuroscience, neural correlates to musical beat perception have been identified, yet little to no …

Bridging The Gap Between Muscle And Bone: Examining Tendon Identity And Development, Amel Sassi

Undergraduate Student Research Internships Conference

Tendons are fibrous connective tissues that connect skeletal muscle to bone. Functioning primarily to facilitate locomotion, these tissues are rich with collagen and other minor collagens and proteoglycans. Nevertheless, with over 4000 tendons in the human body, the molecular pathways that define different tendons remain largely unknown. As such, the clear distinction between tendon identity, particularly at the genetic level has yet to be fully established. Similarly, molecular pathways involved in tendon developments remain to be fully elucidated. Despite the important role of tendons in motor coordination and posture, a number of areas in tendon development and identity have yet …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Evolutionary Conserved Swi/Snf Subunits Arid1a And Arid1b Are Key Modulators Of Pluripotency And Cell-Fate Determination, Luca Pagliaroli, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Organismal development is a process that requires a fine-tuned control of cell fate and identity, through timely regulation of lineage-specific genes. These processes are mediated by the concerted action of transcription factors and protein complexes that orchestrate the interaction between cis-regulatory elements (enhancers, promoters) and RNA Polymerase II to elicit transcription. A proper understanding of these dynamics is essential to elucidate the mechanisms underlying developmental diseases. Many developmental disorders, such as Coffin-Siris Syndrome, characterized by growth impairment and intellectual disability are associated with mutations in subunits of the SWI/SNF chromatin remodeler complex, which is an essential regulator of transcription. ARID1B …

Tgfβ Provides The Backbone Of Embryogenesis: Elucidating The Role Of Tgfβ Signaling And Its Downstream Effectors On Spinal Column Development, Sade Williams Clayton

All ETDs from UAB

The spinal column is composed of two components, the vertebra (VB) that provide support and the intervertebral disc (IVD) that provide weight distribution. The structural integrity of IVDs is maintained by a fibrocartilaginous tissue called the annulus fibrosus (AF) which can degenerate with age or trauma and contribute to chronic back pain. There are currently no diseases modifying treatments that curb IVD degeneration. Regenerative therapies to treat IVD degeneration can be developed from identifying the signaling factors required for AF differentiation, but these factors are unknown. Previously, we showed that TGFβ signaling is required for AF formation in mice and …

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …

The Characterization Of Hematopoiesis In Murine Fetal Bone Marrow, Trent Daniel Hall

Theses and Dissertations (ETD)

Hematopoietic stem cells (HSCs) and their downstream progenitors are a heterogeneous population of cells that are indispensable for lifelong hematopoiesis and are often utilized in the clinic for the treatment of hematologic maladies via hematopoietic stem cell transplantation (HSCT). Over several decades, it has been discovered that HSCs arise in the dorsal aorta of the developing embryo, migrate to the fetal liver (FL), and undergo a large expansion before reaching their final resting place in the bone marrow (BM). Many resources have been invested in understanding the roles of the different niches HSCs encounter along their journey. A greater understanding …

Characterizing The Development Of Episodic Memory And Assessing The Reliability Of Fmri Measures, Lingfei Tang

Wayne State University Dissertations

The ability to remember past events is critical for everyday life and showed robust improvement over development from childhood to adulthood. With advances in noninvasive neuroimaging methods such as functional MRI in recent years, research efforts have been focused on identifying neural correlates underpinning developmental gains in memory performance. In my dissertation work, using a widely-validated subsequent memory paradigm, I aim to characterize functional MRI correlates of memory development. Specifically, I focused my investigation on identifying age differences in the functional patterns of two brain regions critical for memory, the prefrontal cortex and the hippocampus. Focusing on the prefrontal cortex …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu

Biomedical Sciences

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 …

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Electronic Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

Effect Of Resveratrol On The Development Of Eczema, Christopher Carlucci

Theses and Dissertations

Atopic dermatitis is a type of eczema characterized by chronic inflammation of the skin, affecting millions of people worldwide. Resveratrol, a naturally occurring stilbenoid, is widely believed to exhibit beneficial effects on a host of chronic diseases. Although some previous studies have aimed to evaluate the effects of resveratrol on the pathogenesis of atopic dermatitis, this relationship remains ill-defined. We have previously established that mast cell activation, remodeling, and cellular infiltration in the hypodermis all begin prior to the IgE-mediated immune response in an atopic dermatitis mouse model, and that this early pathogenesis is directly related to an increase in …

Neuronal Reorganization In Adult Rats Neonatally Exposed To (±)-3,4-Methylenedioxymethamphetamine, Michael T. Williams, Matthew R. Skelton, Ian D. Longacre, Kimberly N. Huggins, Amanda M. Maple, Charles V. Vorhees, Russell W. Brown

Russell W. Brown

The abuse of methylenedioxymethamphetamine (MDMA) during pregnancy is of concern. MDMA treatment of rats during a period of brain growth analogous to late human gestation leads to neurochemical and behavioral changes. MDMA from postnatal day (P)11–20 in rats produces reductions in serotonin and deficits in spatial and route-based navigation. In this experiment we examined the impact of MDMA from P11 to P20 (20 mg/kg twice daily, 8 h apart) on neuronal architecture. Golgi impregnated sections showed significant changes. In the nucleus accumbens, the dendrites were shorter with fewer spines, whereas in the dentate gyrus the dendritic length was decreased but …

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system …

Epigenetic Profiling Reveals A Developmental Decrease In Promoter Accessibility During Cortical Maturation In Vivo, Ishwariya Venkatesh, Matthew T. Simpson, Denise M. Coley, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve …

Pruning Or Tuning? Maturational Profiles Of Face Specialization During Typical Development, Xun Zhu, Ramesh S. Bhatt, Jane E. Joseph

Psychology Faculty Publications

Introduction: Face processing undergoes significant developmental change with age. Two kinds of developmental changes in face specialization were examined in this study: specialized maturation, or the continued tuning of a region to faces but little change in the tuning to other categories; and competitive interactions, or the continued tuning to faces accompanied by decreased tuning to nonfaces (i.e., pruning). Methods: Using fMRI, in regions where adults showed a face preference, a face- and object-specialization index were computed for younger children (5-8 years), older children (9-12 years) and adults (18-45 years). The specialization index was scaled to each subject's maximum activation …

Human Neural Progenitor Cells Are Productively Infected By R5-Tropic Hiv-1: Opiate Interactions On Infection And Function Involve Cdk5 Signaling, Joyce Magat Balinang

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) is known to cause a spectrum of neurological, behavioral and motor deficits collectively termed as HIV-1 associated neurocognitive impairments (HAND). Opiates augment HIV-related CNS complications through both direct and indirect mechanisms that disrupt glial and neuronal function. All CNS macroglia and neurons derive from neural progenitor cells (NPCs) during development, and NPCs in the adult brain contribute to repair processes. Since disruptions in NPC function are known to impact CNS populations and brain function in a number of disease/injury conditions, we determined whether HIV ± opiate exposure affected the maturation and fate of human …

Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of …

Neural Correlates Of Episodic Memory Formation In Children And Adults, Lingfei Tang

Wayne State University Theses

The medial temporal lobe (MTL) and prefrontal cortex (PFC) are two key brain regions that support episodic memory formation in both children and adults, but the functional developmental of these regions remains unclear. In this study, we investigated the development of neural correlates of episodic memory formation using functional MRI with a subsequent memory paradigm, administered to a cross-sectional sample of 83 children and adults. We found that MTL subregions showed an age-related increase in activation supporting memory formation of complex scenes. In addition, a functionally defined scene-sensitive region in the posterior MTL also showed similar increase and predicted better …

Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans

Theses and Dissertations (ETD)

The blood-brain barrier (BBB) maintains a homeostatic environment as well as prohibits the entrance of xenobiotics into the brain. Because of these qualities, drug delivery is a fundamental challenge for the treatment of many diseases of the central nervous system (CNS). Along with limiting the access of therapeutics into the brain, the BBB is also impaired in CNS pathologies. Understanding the molecular cues that are essential for healthy BBB development and integrity may reveal targets for drug delivery leading to decreased progression or possible treatment of many detrimental CNS diseases. While the central features of the BBB have been accepted, …