Graduate Recital: Natalie Stawarski

Kemp Recital HallApril 13, 2014Sunday Afternoon1:30 p.m

Diseño de mobiliario para la realización de disciplinas artísticas

El origen de este proyecto surge de la propuestade dos proyectos que convergen en uno desarrolladosdurante mi estancia de Erasmus enPoznan, Polonia. Este proyecto se desarrollódurante el segundo semestre del curso 2018-2019 y la temática está inspirada y motivadapor mi experiencia académica cursando disciplinasartísticas dentro de la Escuela de Artesde Poznan.Partiendo de una temática determinada “Staticsand Dynamics”, se propone como proyectocomún dentro del departamento de Diseñode Producto de la Universidad de Artes de Poznanel diseño de dos piezas de mobiliario: unade ellas una superficie estable para colocarelementos, y un asiento en movimiento parasentarse. Estas propuestas parten de dos estudiosdentro del departamento: Estudio de diseñointerdisciplinar (Profesor Michal Filipiak)y Estudio de diseño industrial (Profesor LukaszStawarski).Siguiendo la metodología utilizada en estaescuela, el proyecto parte de la exploraciónde formas a través de modelos físicos y la exploraciónde referencias anteriores en diseñode mobiliario. Posteriormente se ha llevado acabo un estudio del usuario y el entorno comúnal que van dirigidos los productos y undesarrollo funcional y formal de los mismos.Los productos diseñados han sido una silla móvily una mesa regulable. El diseño de los dosproductos para el entorno común derivó en eldiseño adicional de un accesorio común paraambos, se trata de un imán adaptable a diferentesherramientas dentro de este ámbito.<br /

Fakomatozy – znaczenie badań genetycznych dla personalizacji postępowania klinicznego (część 2)

Von Hippel-Lindau disease and tuberous sclerosis are rare genetic disorders, which belong to the group of phacomatoses. They involve an increased risk of development of multiple cancers, mostly benign ones, which may undergo malignant transformation. Genetic diagnostic including identification of the pathogenic variant of the VHL and TSC1 and TSC2 genes enables optimisation of patient care and identification of relatives who carry the mutation.Choroba von Hippla i Lindaua (VHL) oraz stwardnienie guzowate są rzadko występującymi schorzeniami uwarunkowanymi genetycznie, należącymi do grupy fakomatoz. W ich przebiegu występuje zwiększone ryzyko rozwoju mnogich nowotworów, głównie o charakterze łagodnym, które mogą ulegać transformacji do formy złośliwej. Diagnostyka genetyczna obejmująca identyfikację wariantu patogennego genów VHL i TSC1 oraz TSC2 umożliwia optymalizację opieki nad pacjentami oraz typowanie krewnych obciążonych mutacją

Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration)

Characterization of a de novo GABBR2 variant linked to autism spectrum disorder

GABAB receptors (GABABRs) are G protein-coupled receptors for γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Pathogenic variants in the GABBR1 and GABBR2 genes, which encode the GB1 and GB2 subunits of GABABRs, are implicated in several neurological and developmental disorders, including epilepsy and autism. Here we present a 7-year-old boy with Level 3 Autism Spectrum Disorder who carries a de novo heterozygous missense GABBR2 p.Arg212Gln variant. This variant was identified through whole exome sequencing and classified as variant of unknown significance (VUS). Treatment with the GABABR agonist baclofen showed no clinical improvement, raising the question whether this VUS is responsible for the patient’s phenotype. We conducted a study to investigate the impact of the GABBR2 p.Arg212Gln and the previously reported GABBR2 p.Arg212Trp variants on protein structure and receptor activity. This study utilized a combination of molecular dynamics (MD) simulations, and in vitro experiments. Our simulations demonstrate that both amino acid substitutions locally alter amino acid interactions in the extracellular domain of GB2. Most importantly, the substitutions influence the positioning of transmembrane helices, shifting the conformation towards an active state with GABBR2 p.Arg212Gln and an inactive state with GABBR2 p.Arg212Trp. Functional assays confirmed the MD predictions, as evidenced by increased constitutive activity and enhanced potency of GABA for GABBR2 p.Arg212Gln, and a decreased constitutive activity with a loss of GABA potency for GABBR2 p.Arg212Trp. Our findings demonstrate the utility of MD simulations in predicting the functional consequences of VUS. Clarifying the pathogenic mechanisms associated with gene variants will aid in the identification of personalized treatment approaches

Computational Approach to Dendritic Spine Taxonomy and Shape Transition Analysis

The common approach in morphological analysis of dendritic spines of mammalian neuronal cells is to categorize spines into subpopulations based on whether they are stubby, mushroom, thin, or filopodia shaped. The corresponding cellular models of synaptic plasticity, long-term potentiation, and long-term depression associate the synaptic strength with either spine enlargement or spine shrinkage. Although a variety of automatic spine segmentation and feature extraction methods were developed recently, no approaches allowing for an automatic and unbiased distinction between dendritic spine subpopulations and detailed computational models of spine behavior exist. We propose an automatic and statistically based method for the unsupervised construction of spine shape taxonomy based on arbitrary features. The taxonomy is then utilized in the newly introduced computational model of behavior, which relies on transitions between shapes. Models of different populations are compared using supplied bootstrap-based statistical tests. We compared two populations of spines at two time points. The first population was stimulated with long-term potentiation, and the other in the resting state was used as a control. The comparison of shape transition characteristics allowed us to identify the differences between population behaviors. Although some extreme changes were observed in the stimulated population, statistically significant differences were found only when whole models were compared. The source code of our software is freely available for non-commercial use1

Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease

BACKGROUND: Treatment of mild-moderate Alzheimer’s disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. METHODS: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated). We utilized multiplex Xmap technology to measure markers of neurodegenerative disease and metalloproteinases (MMPs) in parallel in CSF and plasma samples. RESULTS: Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2. Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12P40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination (MMSE) scores, change in ADL (ADCS-ADL) scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels. CONCLUSIONS: Collectively, these data suggest that resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. SIRT1 activation may be a viable target for treatment or prevention of neurodegenerative disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT0150485

Place Construction, Identity, and Capital Investment: An investigation of two tourist landscapes in Michigan

Tourist communities exist all over the world. They are areas that are focused on tourism and are often tailored to resemble specific regions or themes to better achieve capital gain. In this study, two cities in Michigan are examined to better understand how the cultural landscapes are experienced and what practices are employed throughout the landscape. Specifically, this thesis investigates the spatial practices that are involved in re-creating and re-presenting ―themed‖ landscapes. Another question analyzed is whether the ―themed‖ landscapes reflect the resident‘s daily lives and/or their histories. This thesis examines the two Michigan cities of Gaylord and Frankenmuth, re-presenting and re-creating Alpenfest and Frankenmuth, respectively, and their emphasis on tourism within their respective communities. To better understand the cultural environment and themed landscapes, digital images are used throughout this thesis of both cities. The data for these themed landscapes were geocoded and analyzed. Also, photographs of both cities were used to demonstrate that only modifications to the façade and additions to the structures were merely aesthetic in nature, and are not realistic but stereotypes of the regions they were representing.Andrew StawarskiGatrell, JayGregory BierlyDavid J. Nemeth(University of Toledo)Master of ArtsDepartment of Earth and Environmental ScienceCunningham Memorial library, Terre Haute, Indiana State University20110720-010MastersTitle from document title page. Document formatted into pages: contains 68p.: ill. Includes abstract

Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children