Visual Replacement Projects

Contains reports on two research projects

Sensory Replacement

Contains a report on a research project.Purchase Order DDL-B15

Visual Replacement Projects

Contains reports on two research projects

The Addition of Arachidin 1 or Arachidin 3 to Human Rotavirus-infected Cells Inhibits Viral Replication and Alters the Apoptotic Cell Death Pathway

Rotavirus (RV) infections are a leading cause of severe gastroenteritis in infants and children under the age of five. There are two vaccines available in the United States and one in India that can be administered early in childhood, however they only protect against specific strains1. From our previous work, both arachidin-1 (A1) and arachidin-3 (A3) from peanut (Arachis hypogaea) hairy root cultures significantly inhibit simian RV replication2,3,4. The purpose of this study was to determine if a human intestinal cell line, HT29.f8, infected with a human RV, Wa, was affected by A1 and A3. Cell viability assays were utilized to determine if A1 and A3 affect the HT29.f8 cells with/without RV infections. At eighteen hours post infection (hpi), supernatants from the RV-infected HT29.f8 cells with/without the arachidins were used in plaque forming assays to quantify and compare the amount of infectious RV particles that are produced during an infection. Transmission electron microscopy (TEM) was used to visualize cell ultrastructure and individual RV particles. Additionally, tunable resistive pulse sensing technology (TRPS) using the qNano system by IZON was employed to quantify and measure virus particle sizes, and display the size distribution of RV particles. Likewise, quantitative real time polymerase chain reactions (qRT-PCR) were performed to determine if A1 and A3 regulated cell death pathways in the HT29.f8 cell line. This data will guide our future studies to determine the antiviral mechanism(s) of action of A1 and A3

A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia

Background. Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Methods. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. Results. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. Conclusions. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection

Higher education disability professionals perceptions on transition processes for college freshmen with autism spectrum disorders

The purpose of this qualitative study was to analyze the perceptions of 14 higher education disability professions (HEDPs) from 4-year public universities in Michigan regarding the transition process for students with autism spectrum disorder (ASD) from secondary to postsecondary institutions. A phenomenological analysis approach was used to analyze data. ASD is a lifelong disorder, and people with ASD who seek postsecondary education require individualized supports. Additionally, a growing number of students with ASD are attending college after high school, so universities need to be prepared for them. ASD students have unique communication, social, and behavioral characteristics and need accommodations to help them achieve academic success. The transition to college can be arduous for these students, and a failure to plan appropriately will nearly always lead to the first-semester failure. Virtual interviews were conducted with participants in which they responded to a 21- question survey instrument that was developed for this study. Five research questions examined retention, barriers, gaps, support services, and practices. Open-ended interviews provided key data, which I analyzed using a theoretical framework informed by transformative worldview inquiry, disability theory, organizational theory, and critical race theory. Nine themes and multiple subthemes emerged from this analysis. These themes identified key factors impacting the postsecondary transition process for students with ASD: parental involvement, accommodations, influencers of success, social and independent functioning, ASD issues, career employment, the transition from K-12 to postsecondary, faculty, and academic functioning. The appendices contain supportive materials to guide the potential implementation of this study for stakeholders: Transition from High School to College Overview Tool, Transition Tool for Students with Autism for College, Transition Tool for Parents, and Informal Inventory for Schools. These tools assist with understanding the key elements that support a successful transition to college for students with autism

THE REGULATION OF ROTAVIRUS–INFECTED HT29.F8 AND MA104 CELLS TREATED WITH ARACHIDIN 1 OR ARACHIDIN 3

Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line (HT29.f8) and an African green monkey kidney cell line (MA104) treated with/without either arachidin. Both cell lines demonstrated apoptotic characteristics that were modulated with the addition of either A1 or A3, and the size and population of the released virus particles were significantly altered. Likewise, the number of infectious virus particles released from the arachidin treated cells were significantly reduced. This data supports the RV therapeutic potential of A1 and A3

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB

OBJECTIVE: Hypoxia affects body iron homeostasis; however, the underlying mechanisms are incompletely understood. DESIGN: Using a standardised hypoxia chamber, 23 healthy volunteers were subjected to hypoxic conditions, equivalent to an altitude of 5600 m, for 6 h. Subsequent experiments were performed in C57BL/6 mice, CREB-H knockout mice, primary hepatocytes and HepG2 cells. RESULTS: Exposure of subjects to hypoxia resulted in a significant decrease of serum levels of the master regulator of iron homeostasis hepcidin and elevated concentrations of platelet derived growth factor (PDGF)-BB. Using correlation analysis, we identified PDGF-BB to be associated with hypoxia mediated hepcidin repression in humans. We then exposed mice to hypoxia using a standardised chamber and observed downregulation of hepatic hepcidin mRNA expression that was paralleled by elevated serum PDGF-BB protein concentrations and higher serum iron levels as compared with mice housed under normoxic conditions. PDGF-BB treatment in vitro and in vivo resulted in suppression of both steady state and BMP6 inducible hepcidin expression. Mechanistically, PDGF-BB inhibits hepcidin transcription by downregulating the protein expression of the transcription factors CREB and CREB-H, and pharmacological blockade or genetic ablation of these pathways abrogated the effects of PDGF-BB toward hepcidin expression. CONCLUSIONS: Hypoxia decreases hepatic hepcidin expression by a novel regulatory pathway exerted via PDGF-BB, leading to increased availability of circulating iron that can be used for erythropoiesis