A5019457074- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Cell Image Analysis Techniques
- Axon Guidance and Neuronal Signaling
- Ubiquitin and proteasome pathways
- Zebrafish Biomedical Research Applications
- Cellular transport and secretion
- Glaucoma and retinal disorders
- Receptor Mechanisms and Signaling
- Pesticide Residue Analysis and Safety
- Cell Adhesion Molecules Research
- Retinal Imaging and Analysis
- Advanced Fluorescence Microscopy Techniques
- Toxic Organic Pollutants Impact
- Genetics and Neurodevelopmental Disorders
- Effects and risks of endocrine disrupting chemicals
- Chromosomal and Genetic Variations
- Down syndrome and intellectual disability research
- Neurobiology and Insect Physiology Research
- Retinal Diseases and Treatments
- Fungal and yeast genetics research
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Per- and polyfluoroalkyl substances research
University of Idaho
2014-2023
University of Washington
2014-2023
Wake Forest University
2023
Wildlife Management Institute
2015-2016
European Food Safety Authority
2015
Chemisches und Veterinäruntersuchungsamt Münsterland-Emscher-Lippe
2008-2014
University of Washington Medical Center
2013
Jackson Laboratory
2006-2011
Novartis (Switzerland)
1998-2010
Novartis Institutes for BioMedical Research
2004-2010
Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma common neurodegenerative disease in which levels of NAD decline. We assess the effects nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron glaucoma) normal physiological conditions across range glaucoma relevant insults including mitochondrial stress axon degenerative insults. demonstrate cell somal, axonal, dendritic neuroprotection by rodent...
High-throughput screening (HTS) is a well-established process in lead discovery for pharma and biotech companies now also being set up basic applied research academia some hospitals.Since its first advent the early to mid-1990s, field of HTS has seen not only continuous change technology processes but an adaptation various needs discovery.HTS evolved into quite mature discipline modern drug discovery.Whereas previous years, much emphasis been put toward steady increase capacity...
The transfer of a mixture perfluoroalkyl acids (PFAAs) from contaminated feed into the edible tissues 24 fattening pigs was investigated. Four sulfonic (PFSAs) and three carboxylic (PFCAs) were quantifiable in feed, plasma, tissues, urine. As percentages unexcreted PFAA, substances accumulated plasma (up to 51%), fat, muscle (collectively, meat 40–49%), liver (under 7%), kidney 2%) for most substances. An exception perfluorooctanesulfonic acid (PFOS), with lower affinity (23%) higher (35%)....
Retrotransposons and retroviruses integrate nonrandomly into eukaryotic genomes. For the yeast retrotransposon Ty5, integration preferentially occurs within domains of heterochromatin. Targeting to these locations is determined by interactions between an amino acid sequence motif at C terminus Ty5 integrase (IN) called targeting domain, heterochromatin protein Sir4p. Here we show that new hot spots are created when Sir4p tethered ectopic DNA sites. sites abrogated single substitutions in...
Significance Our findings demonstrate a function for Down syndrome cell adhesion molecule (DSCAM) in the embryonic development of mouse visual system. We found that DSCAM promotes fasciculation and growth axons developing optic pathway, at least part, through homotypic interactions. also shed can act independently direct cell–cell contact to provide growth-promoting signals. Because Dscam mutant phenotypes are mediated dose-dependent manner, these results potentially relevant human syndrome,...
Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research to identify HSA21 genes that cause specific symptoms. cell adhesion molecule (DSCAM) encoded a gene. Previous studies have shown protein level Drosophila homolog DSCAM determines size presynaptic terminals. However, whether triplication contributes development remains unknown. Here, we show levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In Ts65Dn...
Down syndrome (DS) is a developmental disorder caused by third chromosome 21 in humans (Trisomy 21), leading to neurological deficits and cognitive impairment. Studies mouse models of DS suggest that the adult are associated with synaptic learning memory mechanisms, but it unclear whether alterations early wiring refinement neuronal circuits contribute these deficits. Here, we show visual perturbed syndrome. Specifically, find excessive eye-specific segregation retinal axons dorsal lateral...
In this study we develop and use a gain-of-function mouse allele of the Down syndrome cell adhesion molecule ( Dscam ) to complement loss-of-function models. We assay role in promoting death, spacing, laminar targeting neurons developing retina. find that ectopic or overexpression is sufficient drive death. Gain-of-function studies indicate not increase spatial organization, prevent cell-to-cell pairing, promote active avoidance retina, despite similarity phenotype retina phenotypes observed...
Proteasome inhibition is a therapeutic concept of current interest in anticancer research. We report here the design, synthesis, and biological characterization prototypes new class noncovalent proteasome inhibitors showing high activity biochemical cellular assays.
Abstract DSCAMs are cell adhesion molecules that play several important roles in neurodevelopment. Mouse alleles of Dscam identified to date do not survive on an inbred C57BL/6 background, complicating analysis DSCAM‐dependent developmental processes because phenotypic variability related the segregating backgrounds needed for postnatal survival. A novel spontaneous allele , hereafter referred as 2J has been identified. This contains a four base pair duplication exon 19, leading frameshift...
Individual types of retinal neurons are distributed to minimize proximity neighboring cells. Many these same cell extend dendrites provide coverage the surface. These two cardinal features mosaics disrupted, for certain types, in mice deficient Down syndrome adhesion molecule, Dscam, exhibiting an aberrant clustering somata and fasciculation dendrites. The Dscam mutant mouse retina also exhibits excess numbers types. present study compared retinas with Bax knockout retina, which...
Significance Adult neurons are not able to make new connections as easily developing can; however, future therapies aimed at regeneration and repair of neural circuits in the adult nervous system depend critically on formation such connections. Here, we studied a recently discovered cell population that has unusual ability into adulthood, but under normal conditions does grow axons or dendrites, so no cells contacted. We manipulated this induce axon dendrite outgrowth using transgenic...
The differential adhesion hypothesis of development states that patterning organisms, organs and tissues is mediated in large part by expression cell molecules. cues provided molecules are also hypothesized to facilitate specific connectivity within the nervous system. In this study we characterize a novel mouse mutation gene Dscam (Down Syndrome Cell Adhesion Molecule). Vertebrate DSCAM required for normal central system has been best characterized visual regulation number, mosaic...
ABSTRACT The Down syndrome cell adhesion molecule (DSCAM) is required for regulation of number, soma spacing, and type–specific dendrite avoidance in many types retinal ganglion amacrine cells. In this study we assay the organization cells making up outer plexiform layer retina absence Dscam . Some OFF bipolar cells, type 3b 4 had defects arborization mutant retina, whereas other appeared similar to wild type. cone synapses that these project their dendrites were intact, as visualized by...
ABSTRACT In this study, we characterize the retina of spotted gar, Lepisosteus oculatus , a ray‐finned fish. Gar did not undergo whole genome duplication event that occurred at base teleost fish lineage, which includes model species zebrafish and medaka. The divergence gars from lineage availability high‐quality sequence make it uniquely useful to understand how sculpted features visual system, including photoreceptor diversity. We developed reagents cellular organization gar retina,...