Matching Items (258)
Description
Heterochromatin is a repressive chromatin compartment essential for maintaining genomic integrity. A hallmark of heterochromatin is the presence of specialized nonhistone proteins that alter chromatin structure to inhibit transcription and recombination. It is generally assumed that heterochromatin is highly condensed. However, surprisingly little is known about the structure of heterochromatin or its dynamics in solution. In budding yeast, formation of heterochromatin at telomeres and the homothallic silent mating type loci require the Sir3 protein. Here, we use a combination of sedimentation velocity, atomic force microscopy and nucleosomal array capture to characterize the stoichiometry and conformation of Sir3 nucleosomal arrays. The results indicate that Sir3 interacts with nucleosomal arrays with a stoichiometry of two Sir3 monomers per nucleosome. We also find that Sir3 fibres are less compact than canonical magnesium-induced 30 nm fibres. We suggest that heterochromatin proteins promote silencing by ‘coating’ nucleosomal arrays, stabilizing interactions between nucleosomal histones and DNA.
ContributorsSwygert, Sarah G. (Author) / Manning, Benjamin J. (Author) / Senapati, Subhadip (Author) / Kaur, Parminder (Author) / Lindsay, Stuart (Author) / Demeler, Borries (Author) / Peterson, Craig L. (Author) / Biodesign Institute (Contributor) / Single Molecule Biophysics (Contributor)
Created2014-08-01
Description
We studied the microbial community structure of pilot two-stage membrane biofilm reactors (MBfRs) designed to reduce nitrate (NO[subscript 3]–) and perchlorate (ClO[subscript 4]–) in contaminated groundwater. The groundwater also contained oxygen (O[subscript 2]) and sulfate (SO[2 over 4]–), which became important electron sinks that affected the NO[subscript 3]– and ClO[subscript 4]– removal rates. Using pyrosequencing, we elucidated how important phylotypes of each “primary” microbial group, i.e., denitrifying bacteria (DB), perchlorate-reducing bacteria (PRB), and sulfate-reducing bacteria (SRB), responded to changes in electron-acceptor loading. UniFrac, principal coordinate analysis (PCoA), and diversity analyses documented that the microbial community of biofilms sampled when the MBfRs had a high acceptor loading were phylogenetically distant from and less diverse than the microbial community of biofilm samples with lower acceptor loadings. Diminished acceptor loading led to SO[2 over 4]– reduction in the lag MBfR, which allowed Desulfovibrionales (an SRB) and Thiothrichales (sulfur-oxidizers) to thrive through S cycling. As a result of this cooperative relationship, they competed effectively with DB/PRB phylotypes such as Xanthomonadales and Rhodobacterales. Thus, pyrosequencing illustrated that while DB, PRB, and SRB responded predictably to changes in acceptor loading, a decrease in total acceptor loading led to important shifts within the “primary” groups, the onset of other members (e.g., Thiothrichales), and overall greater diversity.
ContributorsOntiveros-Valencia, Aura (Author) / Tang, Youneng (Author) / Zhao, Heping (Author) / Friese, David (Author) / Overstreet, Ryan (Author) / Smith, Jennifer (Author) / Evans, Patrick (Author) / Rittmann, Bruce (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor) / Swette Center for Environmental Biotechnology (Contributor) / Julie Ann Wrigley Global Institute of Sustainability (Contributor) / School of Sustainability (Contributor)
Created2014-07-01
Description
The Combined Activated Sludge-Anaerobic Digestion Model (CASADM) quantifies the effects of recycling anaerobic-digester (AD) sludge on the performance of a hybrid activated sludge (AS)-AD system. The model includes nitrification, denitrification, hydrolysis, fermentation, methanogenesis, and production/utilization of soluble microbial products and extracellular polymeric substances (EPS). A CASADM example shows that, while effluent COD and N are not changed much by hybrid operation, the hybrid system gives increased methane production in the AD and decreased sludge wasting, both caused mainly by a negative actual solids retention time in the hybrid AD. Increased retention of biomass and EPS allows for more hydrolysis and conversion to methane in the hybrid AD. However, fermenters and methanogens survive in the AS, allowing significant methane production in the settler and thickener of both systems, and AD sludge recycle makes methane formation greater in the hybrid system.
ContributorsYoung, Michelle (Author) / Marcus, Andrew (Author) / Rittmann, Bruce (Author) / Biodesign Institute (Contributor) / Swette Center for Environmental Biotechnology (Contributor)
Created2013-08-13
Description
Background
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
ContributorsZhang, Wenlu (Author) / Feng, Daming (Author) / Li, Rongjian (Author) / Chernikov, Andrey (Author) / Chrisochoides, Nikos (Author) / Osgood, Christopher (Author) / Konikoff, Charlotte (Author) / Newfeld, Stuart (Author) / Kumar, Sudhir (Author) / Ji, Shuiwang (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2013-12-28
Learning Sparse Representations for Fruit-Fly Gene Expression Pattern Image Annotation and Retrieval
Description
Background
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
ContributorsYuan, Lei (Author) / Woodard, Alexander (Author) / Ji, Shuiwang (Author) / Jiang, Yuan (Author) / Zhou, Zhi-Hua (Author) / Kumar, Sudhir (Author) / Ye, Jieping (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2012-05-23
Description
Coronaviruses are a significant group of viruses that cause enteric and respiratory infections in a variety of animals, including humans. Outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) in the past 15 years has increased research into coronaviruses to gain an understanding of their structure and function so one day therapies and vaccines may be produced. These viruses have four main structural proteins: the spike, nucleocapsid, envelope, and membrane proteins. The envelope (E) protein is an integral membrane protein in the viral envelope that acts as a viroporin for transport of cations and plays an important role in pathogenesis and viral assembly. E contains a hydrophobic transmembrane domain with polar residues that is conserved across coronavirus species and may be significant to its function. This experiment looks at the possible role of one polar residue in assembly, the 15th residue glutamine, in the Mouse Hepatitis Virus (MHV) E protein. The glutamine 15 residue was mutated into positively charged residues lysine or arginine. Plasmids with these mutations were co-expressed with the membrane protein (M) gene to produce virus-like particles (VLPs). VLPs are produced when E and M are co-expressed together and model assembly of the coronavirus envelope, but they are not infectious as they do not contain the viral genome. Observing their production with the mutated E protein gives insight into the role the glutamine residue plays in assembly. The experiment showed that a changing glutamine 15 to positive charges does not appear to significantly affect the assembly of the VLPs, indicating that this specific residue may not have a large impact on viral assembly.
ContributorsHaller, Sarah S. (Author) / Hogue, Brenda (Thesis director) / Liu, Wei (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor) / Biodesign Institute (Contributor)
Created2017-05
Description
This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials. These novel tests can be easily implemented by owners, veterinarians, and clinicians and therefore, may improve care for elderly dogs by aiding in the diagnosis of dementia. In addition, these widely deployable tests may facilitate the use of dementia in pet dogs as a naturally occurring model of Alzheimer’s Disease in humans.In Chapters 4 and 5, I modified one of these tests to demonstrate for the first time that coyotes (Canis latrans) and wolves (Canis lupus lupus) develop age-related deficits in cognitive flexibility. This was an important first step towards differentiating between the genetic and environmental components of dementia in dogs and in turn, humans. Unexpectedly, I also detected cognitive deficits in young, adult dogs and wolves but not coyotes. These finding add to a recent shift in understanding cognitive development in dogs which may improve cognitive aging tests as well as training, care, and use of working and pet dogs. These findings also suggest that the ecology of coyotes may select for flexibility earlier in development.
In Chapter 5, I piloted the use of the same cognitive flexibility test for red and gray foxes so that future studies may test for lifespan changes in the cognition of small-bodied captive canids. More broadly, this paradigm may accommodate physical and behavioral differences between diverse pet and captive animals. In Chapters 4 and 5, I examined which ecological traits drive the evolution of behavioral flexibility and in turn, species resilience. I found that wolves displayed less flexibility than dogs and coyotes suggesting that species which do not rely heavily on unstable resources may be ill-equipped to cope with human habitat modification. Ultimately, this comparative work may help conservation practitioners to identify and protect species that cannot cope with rapid and unnatural environmental change.
ContributorsVan Bourg, Joshua (Author) / Wynne, Clive D (Thesis advisor) / Aktipis, C. Athena (Committee member) / Gilby, Ian C (Committee member) / Young, Julie K (Committee member) / Arizona State University (Publisher)
Created2022
Description
ABSTRACT
Domestic dogs have assisted humans for millennia. However, the extent to which these helpful behaviors are prosocially motivated remains unclear. To assess the propensity of pet dogs to spontaneously and actively rescue distressed humans, this study tested whether sixty pet dogs would release their seemingly trapped owners from a large box. To examine the causal mechanisms that shaped this behavior, the readiness of each dog to open the box was tested in three conditions: 1) the owner sat in the box and called for help (“Distress” test), 2) an experimenter placed high-value food rewards in the box (“Food” test), and 3) the owner sat in the box and calmly read aloud (“Reading” test).
Dogs were as likely to release their distressed owner as to retrieve treats from inside the box, indicating that rescuing an owner may be a highly rewarding action for dogs. After accounting for ability, dogs released the owner more often when the owner called for help than when the owner read aloud calmly. In addition, opening latencies decreased with test number in the Distress test but not the Reading test. Thus, rescuing the owner could not be attributed solely to social facilitation, stimulus enhancement, or social contact-seeking behavior.
Dogs displayed more stress behaviors in the Distress test than in the Reading test, and stress scores decreased with test number in the Reading test but not in the Distress test. This evidence of emotional contagion supports the hypothesis that rescuing the distressed owner was an empathetically-motivated prosocial behavior. Success in the Food task and previous (in-home) experience opening objects were both strong predictors of releasing the owner. Thus, prosocial behavior tests for dogs should control for physical ability and previous experience.
Domestic dogs have assisted humans for millennia. However, the extent to which these helpful behaviors are prosocially motivated remains unclear. To assess the propensity of pet dogs to spontaneously and actively rescue distressed humans, this study tested whether sixty pet dogs would release their seemingly trapped owners from a large box. To examine the causal mechanisms that shaped this behavior, the readiness of each dog to open the box was tested in three conditions: 1) the owner sat in the box and called for help (“Distress” test), 2) an experimenter placed high-value food rewards in the box (“Food” test), and 3) the owner sat in the box and calmly read aloud (“Reading” test).
Dogs were as likely to release their distressed owner as to retrieve treats from inside the box, indicating that rescuing an owner may be a highly rewarding action for dogs. After accounting for ability, dogs released the owner more often when the owner called for help than when the owner read aloud calmly. In addition, opening latencies decreased with test number in the Distress test but not the Reading test. Thus, rescuing the owner could not be attributed solely to social facilitation, stimulus enhancement, or social contact-seeking behavior.
Dogs displayed more stress behaviors in the Distress test than in the Reading test, and stress scores decreased with test number in the Reading test but not in the Distress test. This evidence of emotional contagion supports the hypothesis that rescuing the distressed owner was an empathetically-motivated prosocial behavior. Success in the Food task and previous (in-home) experience opening objects were both strong predictors of releasing the owner. Thus, prosocial behavior tests for dogs should control for physical ability and previous experience.
ContributorsVan Bourg, Joshua Lazar (Author) / Wynne, Clive D (Thesis advisor) / Gilby, Ian C (Committee member) / Aktipis, C. Athena (Committee member) / Arizona State University (Publisher)
Created2019
Description
Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.
ContributorsTrenchevska, Olgica (Author) / Phillips, David A. (Author) / Nelson, Randall (Author) / Nedelkov, Dobrin (Author) / Biodesign Institute (Contributor)
Created2014-06-23
Description
This work suggests an effective approach to fabricate reduced graphene oxide-based carbon (RGO/C) composite films. The carbonization of graphene oxide-reinforced polyimide (GO/PI) composite films was investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The crystalline structures and carbonized mechanism of the RGO/C composite films were investigated in detail by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Furthermore, the carbonization yields were improved due to the catalytic effects of RGO. These RGO/C composite films exhibited obvious structural orientations by SEM investigation of their cross sections.
ContributorsNiu, Yongan (Author) / Zhang, Xin (Author) / Zhao, Jiupeng (Author) / Tian, Yanqing (Author) / Yan, Xiangqiao (Author) / Li, Yao (Author) / Biodesign Institute (Contributor)
Created2014-04-11