Digital Commons Network^™

Identification Of Biomarkers That Distinguish Chemical Contaminants Based On Gene Expression Profiles, Xiaomou Wei, Junmei Ai, Youping Deng, Xin Guan, David R. Johnson, Choo Y. Ang, Chaoyang Zhang, Edward J. Perkins

Faculty Publications

Background: High throughput transcriptomics profiles such as those generated using microarrays have been useful in identifying biomarkers for different classification and toxicity prediction purposes. Here, we investigated the use of microarrays to predict chemical toxicants and their possible mechanisms of action.

Results: In this study, in vitro cultures of primary rat hepatocytes were exposed to 105 chemicals and vehicle controls, representing 14 compound classes. We comprehensively compared various normalization of gene expression profiles, feature selection and classification algorithms for the classification of these 105 chemicals into14 compound classes. We found that normalization had little effect on the averaged …

Mir-200, A New Star Mirna In Human Cancer, Xiangling Feng, Zhengming Wang, Rebecca Fillmore, Yaguang Xi

Faculty Publications

MicroRNAs (miRNAs) are a set of non-coding small RNA molecules in control of gene expression at posttranscriptional/translational level. They not only play crucial roles in normal developmental progress, but also are commonly dysregulated in human diseases, including cancer. MiR-200 is a family of tumor suppressor miRNAs consisting of five members, which are significantly involved in inhibition of epithelial-to-mesenchymal transition (EMT), repression of cancer stem cells (CSCs) self-renewal and differentiation, modulation of cell division and apoptosis, and reversal of chemoresistance. In this article, we summarize the latest findings with regard to the tumor suppressor signatures of miR-200 and the regulatory mechanisms …

The Structure Of Human 15-Lipoxygenase-2 With A Substrate Mimic, Matthew J. Kobe, David B. Neau, Caitlin E. Mitchell, Sue G. Bartlett, Marcia E. Newcomer

Faculty Publications

Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques.We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca2+-binding sites that confer Ca2+-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures …

Concentrations And Sources Of Polycyclic Aromatic Hydrocarbons In Surface Coastal Sediments Of The Northern Gulf Of Mexico, Zucheng Wang, Zhanfei Liu, Kehui Xu, Lawrence M. Mayer, Zulin Zhang, Alexander S. Kolker, Wei Wu

Faculty Publications

Background: Coastal sediments in the northern Gulf of Mexico have a high potential of being contaminated by petroleum hydrocarbons, such as polycyclic aromatic hydrocarbons (PAHs), due to extensive petroleum exploration and transportation activities. In this study we evaluated the spatial distribution and contamination sources of PAHs, as well as the bioavailable fraction in the bulk PAH pool, in surface marsh and shelf sediments (top 5 cm) of the northern Gulf of Mexico. Results: PAH concentrations in this region ranged from 100 to 856 ng g(-1), with the highest concentrations in Mississippi River mouth sediments followed by marsh sediments and then …

Inundicola Bravo, Isler, And Brumfield 2013 Is A Junior Synonym Of Akletos Dunajewski 1948 (Aves: Passeriformes: Thamnophilidae), Morton L. Isler, Gustavo A. Bravo, Robb T. Brumfield

Faculty Publications

No abstract provided.

Drosophila Snap-29 Is An Essential Snare That Binds Multiple Proteins Involved In Membrane Traffic, Hao Xu, Mahmood Mohtashami, Bryan Stewart, Gabrielle Boulianne, William S. Trimble

Faculty Publications

Each membrane fusion event along the secretory and endocytic pathways requires a specific set of SNAREs to assemble into a 4-helical coiled-coil, the so-called trans-SNARE complex. Although most SNAREs contribute one helix to the trans-SNARE complex, members of the SNAP-25 family contribute two helixes. We report the characterization of the Drosophila homologue of SNAP-29 (dSNAP-29), which is expressed throughout development. Unlike the other SNAP-25 like proteins in fruit fly (i.e., dSNAP-25 and dSNAP-24), which form SDS-resistant SNARE complexes with their cognate SNAREs, dSNAP-29 does not participate in any SDS-resistant complexes, despite its interaction with dsyntaxin1 and dsyntaxin 16 in vitro. …

Correction Of The Caulobacter Crescentus Na1000 Genome Annotation, Bert Ely, Latia Etheredge Scott

Faculty Publications

Bacterial genome annotations are accumulating rapidly in the GenBank database and the use of automated annotation technologies to create these annotations has become the norm. However, these automated methods commonly result in a small, but significant percentage of genome annotation errors. To improve accuracy and reliability, we analyzed the Caulobacter crescentus NA1000 genome utilizing computer programs Artemis and MICheck to manually examine the third codon position GC content, alignment to a third codon position GC frame plot peak, and matches in the GenBank database. We identified 11 new genes, modified the start site of 113 genes, and changed the reading …

Ancient Pathogen Dna In Archaeological Samples Detected With A Microbial Detection Array, Alison M. Devault, Kevin Mcloughlin, Crystal Jaing, Shea Gardner, Teresita M. Porter, Jacob M. Enk, James Thissen, Jonathan Allen, Monica Borucki, Sharon Dewitte, Anna N. Dhody, Hendrik N. Poinar

Faculty Publications

Ancient human remains of paleopathological interest typically contain highly degraded DNA in which pathogenic taxa are often minority components, making sequence-based metagenomic characterization costly. Microarrays may hold a potential solution to these challenges, offering a rapid, affordable and highly informative snapshot of microbial diversity in complex samples without the lengthy analysis and/or high cost associated with high-throughput sequencing. Their versatility is well established for modern clinical specimens, but they have yet to be applied to ancient remains. Here we report bacterial profiles of archaeological and historical human remains using the Lawrence Livermore Microbial Detection Array (LLMDA). The array successfully identified …

Quantifying The Impact Of Mosquitoes On Quality Of Life And Enjoyment Of Yard And Porch Activities In New Jersey, Yara A. Halasa, Donald S. Shepard, Dina M. Fonseca, Ary Farajollahi, Sean Healy, Randy Gaugler, Kristen Bartlett-Healy, Daniel A. Strickman, Gary G. Clark

Faculty Publications

The recent expansion of Aedes albopictus, a day-biting mosquito, to densely inhabited areas in the northeastern Atlantic states of the USA has dramatically increased the problem that mosquitoes create for urban and suburban residents. We quantified the impact of mosquitoes on residents' quality of life within the context of a comprehensive area-wide integrated pest management program to control Ae. albopictus in two counties (Mercer and Monmouth) in New Jersey. We interviewed residents of 121 randomly selected households in both counties between October and November 2010. We asked residents about their experience with mosquitoes in their neighborhood and the importance of …

Innocence Presumed: A New Analysis Of Innocence As A Constitutional Claim, Paige Kaneb

Faculty Publications

The Supreme Court has never resolved whether innocence is a freestanding constitutional claim. Many critics have mistakenly contended that the Court held in 1993 that innocence is not a federal constitutional claim. As a result, much of the literature has failed to recognize that the door for such claims remains open, or that relevant circumstances have changed and thus the constitutional analysis has changed as well.

In the past two decades, a consensus has emerged among states recognizing the right to judicial review of compelling claims of innocence. In the wake of DNA exonerations, the states reacted uniformly in providing …

What Will It Take To Observe Processes In 'Real Time'?, Stephen R. Leone, C. William Mccurdy, Joachim Burgdörfer, Lorenz S. Cederbaum, Zenghu Chang, Nirit Dudovich, Johannes Feist, Chris H. Greene, Misha Ivanov, Reinhard Kienberger, Ursula Keller, Matthias F. Kling, Zhi Heng Loh, Thomas Pfeifer, Adrian N. Pfeiffer, Robin Santra, Kenneth Schafer, Albert Stolow, Uwe Thumm, Marc J.J. Vrakking

Faculty Publications

No abstract provided.

A Conceptual Framework For Analyzing Social-Ecological Models Of Emerging Infectious Diseases, Melissa L. Finucane, Jefferson Fox, Sumeet Saksena, James H. Spencer

Faculty Publications

Unraveling mechanisms that underlie new and reemerging infectious diseases (EID) requires exploring complex interactions within and among coupled natural and human (CNH) systems. This scientifi c problem poses one of the most diffi cult challenges for society today (Wilcox and Colwell 2005 ). EID are diseases that have recently increased in incidence or in geographic or host range (e.g., tuberculosis, cholera, malaria, dengue fever), and diseases caused by new pathogens and new variants assigned to known pathogens (e.g., HIV, SARS, Nipah virus, and avian infl uenza) (Morse 2005 ). Wilcox and Gubler ( 2005 ) and Wilcox and Colwell ( …

Aircraft Route Optimization For Formation Flight, Jia Xu, Andrew Ning, Geoffrey Bower, Ilan Kroo

Faculty Publications

We quantify the fuel and cost benefits of applying extended formation flight to com- mercial airline operations. Central to this study is the development of a bi-level, mixed integer-real formation flight optimization framework. The framework has two main components: 1) a continuous domain aircraft mission performance optimization and 2) an integer optimization component that selects the best combination of optimized missions to form a formation flight schedule. The mission performance reflects the effects of rolled-up wakes, formation heterogeneity, and formation-induced compressibility. The results show that an airline can use formation flight to reduce fuel burn by 5.8% or direct operating …

Structural And Functional Analyses Of A Glutaminyl Cyclase From Ixodes Scapularis Reveal Metal-Independent Catalysis And Inhibitor Binding, Kai-Fa Huang, Hui-Ling Hsu, Shahid Karim, Andrew H.-J. Wang

Faculty Publications

Glutaminyl cyclases (QCs) from mammals and Drosophila are zinc-dependent enzymes that catalyze N-terminal pyroglutamate formation of numerous proteins and peptides. These enzymes have been found to be critical for the oviposition and embryogenesis of ticks, implying that they are possible physiological targets for tick control. Here, 1.10–1.15 Å resolution structures of a metal-independent QC from the black-legged tick Ixodes scapularis (Is-QC) are reported. The structures exhibit the typical scaffold of mammalian QCs but have two extra disulfide bridges that stabilize the central β-­sheet, resulting in an increased thermal stability. Is-QC contains ∼0.5 stoichiometric zinc ions, which could …

Priming In The Microbial Landscape: Periphytic Algal Stimulation Of Litter-Associated Microbial Decomposers, Kevin A. Kuehn, Steven N. Francoeur, Robert H. Findlay, Robert K. Neely

Faculty Publications

Microbial communities associated with submerged detritus in aquatic ecosystems often comprise a diverse mixture of autotrophic and heterotrophic microbes, including algae, bacteria, protozoa, and fungi. Recent studies have documented increased rates of plant litter mass loss when periphytic algae are present. We conducted laboratory and field experiments to assess potential metabolic interactions between natural autotrophic and heterotrophic microbial communities inhabiting submerged decaying plant litter of Typha angustifolia and Schoenoplectus acutus. In the field, submerged plant litter was either exposed to natural sunlight or placed under experimental canopies that manipulated light availability and growth of periphytic algae. Litter was collected …

Mechanisms Of Soil Carbon Accrual And Storage In Bioenergy Cropping Systems, Lisa K. Tiemann, A. Stuart Grandy

Faculty Publications

Annual row cropping systems converted to perennial bioenergy crops tend to accrue soil C, likely a function of increased root production and decreased frequency of tillage; however, very little is known about the mechanisms governing the accrual and stability of this additional soil C. To address this uncertainty, we assessed the formation and stability of aggregates and soil organic C (SOC) pools under switchgrass, giant miscanthus, a native perennial grass mix and continuous corn treatments in Michigan and Wisconsin soils differing in both texture and mineralogy. We isolated different aggregate size fractions, >2 mm, 0.5–2 mm, and <0.5 mm, using a procedure intended to minimize alterations to aggregate biological and chemical properties. We determined SOC, permanganate oxidizable C (POXC), and microbial activities (i.e. enzyme activities and soil respiration rates) associated with these aggregates. Soil type strongly influenced the trajectory of aggregate formation and stabilization with differences between sites in mean aggregate size, stability, SOC and microbial activity under perennial vs. corn cropping systems. At the Michigan site, soil microbial activities were highest in the >2 mm aggregates, …

Applicability Of Latent Dirichlet Allocation To Multi-Disk Search, George E. Noel, Gilbert L. Peterson

Faculty Publications

Digital forensics practitioners face a continual increase in the volume of data they must analyze, which exacerbates the problem of finding relevant information in a noisy domain. Current technologies make use of keyword based search to isolate relevant documents and minimize false positives with respect to investigative goals. Unfortunately, selecting appropriate keywords is a complex and challenging task. Latent Dirichlet Allocation (LDA) offers a possible way to relax keyword selection by returning topically similar documents. This research compares regular expression search techniques and LDA using the Real Data Corpus (RDC). The RDC, a set of over 2400 disks from real …

Quantifying The Impact Of Atmospheric Deposition On The Biogeochemistry Of Fe And Al In The Upper Ocean: A Decade Of Collaboration With The Us Clivar-Co2 Repeat Hydrography Program, Maxime Grand, Clifton Buck, William Landing, Christopher Measures, Mariko Hatta, William Hiscock, Matthew Brown, Joseph Resing

Faculty Publications

The aerosol deposition of continental material and its partial dissolution in the surface ocean exerts an important control on the distribution of iron and other potentially limiting trace metal (TM) micronutrients in the open ocean. This dust deposition has implications for the regulation of global climate through the coupling of biolimiting TM cycles, marine productivity, and the global carbon cycle. Thus, it is important to determine the locations of dust deposition in the open ocean and to quantify the magnitude and subsequent dissolution of the dust. At present, there are too few dust deposition estimates and solubility measurements in the …

The Induction Of Lipocalin-2 Protein Expression In Vivo And In Vitro, Peng Zhao, Carrie M. Elks, Jacqueline M. Stephens

Faculty Publications

Lipocalin-2 (LCN2) is secreted from adipocytes, and its expression is up-regulated in obese and diabetic mice and humans. LCN2 expression and secretion have been shown to be induced by two proinflammatory cytokines, IFNγ and TNFα, in cultured murine and human adipocytes. In these studies, we demonstrated that IFNγ and TNFα induced LCN2 expression and secretion in vivo. Although we observed a strong induction of LCN2 expression and secretion from white adipose tissue (WAT) depots, the induction of LCN2 varied among different insulin-sensitive tissues. Knockdown experiments also demonstrated that STAT1 is required for IFNγ-induced lipocalin-2 expression in murine adipocytes. Similarly, knockdown …

Bayesian Dose-Finding Designs For Combination Of Molecularly Targeted Agents Assuming Partial Stochastic Ordering, Beibei Guo, Yisheng Li

Faculty Publications

Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose-finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose-efficacy and dose-toxicity models. Motivated by a phase I/II …

Morphological Divergence Driven By Predation Environment Within And Between Species Of Brachyrhaphis Fishes, Spencer J. Ingley, Eric J. Billman, Mark C. Belk, Jerald B. Johnson

Faculty Publications

Natural selection often results in profound differences in body shape among populations from divergent selective environments. Predation is a well-studied driver of divergence, with predators having a strong effect on the evolution of prey body shape, especially for traits related to escape behavior. Comparative studies, both at the population level and between species, show that the presence or absence of predators can alter prey morphology. Although this pattern is well documented in various species or population pairs, few studies have tested for similar patterns of body shape evolution at multiple stages of divergence within a taxonomic group. Here, we examine …

Brief Of Amici Curiae Law, Business, And Economics Scholars In Alice Corp. V. Cls Bank, No. 13-298, Brian J. Love, Jason Schultz, James E. Bessen, Michael J. Meurer

Faculty Publications

The Federal Circuit’s expansion of patentable subject matter in the 1990s led to a threefold increase in software patents, many of which contain abstract ideas merely tethered to a general-purpose computer. There is little evidence, however, to suggest this expansion has produced an increase in software innovation. The software industry was highly innovative in the decade immediately prior to this expansion, when the viability of software patentability was unclear and software patents were few. When surveyed, most software developers oppose software patenting, and, in practice, software innovators tend to rely on other tools to capture market share such as first-mover …

Exploring Local Adaptation And The Ocean Acidification Seascape - Studies In The California Current Large Marine Ecosystem, G. E. Hofmann, T. G. Evans, M. W. Kelly, J. L. Padilla-Gamiño, C. A. Blanchette, L. Washburn, F. Chan, M. A. Mcmanus, B. A. Menge, B. Gaylord, T. M. Hill, E. Sanford, M. Lavigne, J. M. Rose, L. Kapsenberg, J. M. Dutton

Faculty Publications

The California Current Large Marine Ecosystem (CCLME), a temperate marine region dominated by episodic upwelling, is predicted to experience rapid environmental change in the future due to ocean acidification. The aragonite saturation state within the California Current System is predicted to decrease in the future with near-permanent undersaturation conditions expected by the year 2050. Thus, the CCLME is a critical region to study due to the rapid rate of environmental change that resident organisms will experience and because of the economic and societal value of this coastal region. Recent efforts by a research consortium-the Ocean Margin Ecosystems Group for Acidification …

Accessing Near-Infrared-Absorbing Bf2-Azadipyrromethenes Via A Push-Pull Effect, Lijuan Jiao, Yayang Wu, Sufan Wang, Xiaoke Hu, Ping Zhang, Changjiang Yu, Kebing Cong, Qianli Meng, Erhong Hao, M. Graça H. Vicente

Faculty Publications

Novel aza-BODIPYs with significant bathochromic shifts were designed and synthesized by installation of strong electron-withdrawing groups on the para-positions of 1,7-phenyls and electron-donating groups on the para-positions of 3,4-phenyls. These dyes show strong NIR fluorescence emissions up to 756 nm, and absorptions up to 720 nm. © 2014 American Chemical Society.

Surface Assembly And Nanofabrication Of 1,1,1-Tris(Mercaptomethyl)Heptadecane On Au(111) Studied With Time-Lapse Atomic Force Microscopy, Tian Tian, Burapol Singhana, Lauren E. Englade-Franklin, Xianglin Zhai, T. Randall Lee, Jayne C. Garno

Faculty Publications

The solution self-assembly of multidentate organothiols onto Au(111) was studied in situ using scanning probe nanolithography and time-lapse atomic force microscopy (AFM). Self-assembled monolayers (SAMs) prepared from dilute solutions of multidentate thiols were found to assemble slowly, requiring more than six hours to generate films. A clean gold substrate was first imaged in ethanolic media using liquid AFM. Next, a 0.01 mM solution of multidentate thiol was injected into the liquid cell. As time progressed, molecular-level details of the surface changes at different time intervals were captured by successive AFM images. Scanning probe based nanofabrication was accomplished using protocols of …

Pfkfb3 Regulates Oxidative Stress Homeostasis Via Its S-Glutathionylation In Cancer, Minsuh Seo, Yong Hwan Lee

Faculty Publications

Whereas moderately increased cellular oxidative stress is supportive for cancerous growth of cells, excessive levels of reactive oxygen species (ROS) are detrimental to their growth and survival. We demonstrated that high ROS levels, via increased oxidized glutathione (GSSG), induce isoform-specific S-glutathionylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) at residue Cys206, which is located near the entrance to the 6-phosphofructo-2-kinase catalytic pocket. Upon this ROS-dependent, reversible, covalent modification, a marked decrease in its catalytic ability to synthesize fructose-2,6-bisphosphate (Fru-2,6-P2), the key glycolysis allosteric activator, was observed. This event was coupled to a decrease in glycolytic flux and an increase in glucose metabolic flux …

Consistency Between Research And Clinical Diagnoses Of Autism Among Boys And Girls With Fragile X Syndrome, Jessica Klusek, G E. Martin, M Losh

Faculty Publications

No abstract provided.

Plastid Phylogenomics And Green Plant Phylogeny: Almost Full Circle But Not Quite There, Charles C. Davis, Zhenxiang Xi, Sarah Mathews

Faculty Publications

A study in BMC Evolutionary Biology represents the most comprehensive effort to clarify the phylogeny of green plants using sequences from the plastid genome. This study highlights the strengths and limitations of plastome data for resolving the green plant phylogeny, and points toward an exciting future for plant phylogenetics, during which the vast and largely untapped territory of nuclear genomes will be explored. © 2014 Davis et al.; licensee BioMed Central Ltd.

Capillary Electrophoresis-Based Assay Of Phosphofructokinase-1, Andrew Malina, Sherrisse K. Bryant, Simon H. Chang, Grover L. Waldrop, S. Douglass Gilman

Faculty Publications

An assay was developed for phosphofructokinase-1 (PFK-1) using capillary electrophoresis (CE). In the glycolytic pathway, this enzyme catalyzes the rate-limiting step from fructose-6-phosphate and magnesium-bound adenosine triphosphate (Mg-ATP) to fructose-1,6-bisphosphate and magnesium-bound adenosine diphosphate (Mg-ADP). This enzyme has recently become a research target because of the importance of glycolysis in cancer and obesity. The CE assay for PFK-1 is based on the separation and detection by ultraviolet (UV) absorbance at 260 nm of Mg-ATP and Mg-ADP. The separation was enhanced by the addition of Mg 2+ to the separation buffer. Inhibition studies of PFK-1 by aurintricarboxylic acid and palmitoyl coenzyme …

Redox Control Of Human Mitochondrial Outer Membrane Protein Mitoneet [2fe-2s] Clusters By Biological Thiols And Hydrogen Peroxide, Aaron P. Landry, Huangen Ding

Faculty Publications

Background: MitoNEET is a target of the type II diabetes drug pioglitazone and contains a [2Fe-2S] cluster. Results: The mitoNEET [2Fe-2S] cluster can be reduced by biological thiols and reversibly oxidized by hydrogen peroxide. Conclusion: The redox state of mitoNEET [2Fe-2S] clusters can be regulated by thiols and oxidative signals. Significance: MitoNEET may act as a redox sensor to modulate mitochondrial functions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc..