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Systems Modeling Accurately Predicts Responses To Genotoxic Agents And Their Synergism With Bcl-2 Inhibitors In Triple Negative Breast Cancer Cells., Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen HM Prehn 2018 Royal College of Surgeons in Ireland

Systems Modeling Accurately Predicts Responses To Genotoxic Agents And Their Synergism With Bcl-2 Inhibitors In Triple Negative Breast Cancer Cells., Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen Hm Prehn

Physiology and Medical Physics Articles

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells ...


The Mayfly Newsletter, Donna J. Giberson 2018 The Permanent Committee of the International Conferences on Ephemeroptera

The Mayfly Newsletter, Donna J. Giberson

The Mayfly Newsletter

No abstract provided.


Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler 2018 George Washington University

Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler

Genomics and Precision Medicine Faculty Publications

Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic ...


Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +several additional authors 2018 George Washington University

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in ...


Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler 2018 ETH Zurich

Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis Du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler

Ecology, Evolution and Organismal Biology Publications

Phylogenetics and phylodynamics are central topics in modern evolutionary biology. Phylogenetic methods reconstruct the evolutionary relationships among organisms, whereas phylodynamic approaches reveal the underlying diversification processes that lead to the observed relationships. These two fields have many practical applications in disciplines as diverse as epidemiology, developmental biology, palaeontology, ecology, and linguistics. The combination of increasingly large genetic data sets and increases in computing power is facilitating the development of more sophisticated phylogenetic and phylodynamic methods. Big data sets allow us to answer complex questions. However, since the required analyses are highly specific to the particular data set and question, a ...


Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley 2017 George Washington University

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Genomics and Precision Medicine Faculty Publications

Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 ...


24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +several additional authors 2017 George Washington University

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9 ...


The Hoxd Cluster Is A Dynamic And Resilient Tad Boundary Controlling The Segregation Of Antagonistic Regulatory Landscapes, Eddie Rodriguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J. Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule 2017 University of Geneva

The Hoxd Cluster Is A Dynamic And Resilient Tad Boundary Controlling The Segregation Of Antagonistic Regulatory Landscapes, Eddie Rodriguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J. Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule

Program in Systems Biology Publications and Presentations

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region ...


A Systems Level Approach To Temporal Expression Dynamics In Drosophila Reveals Clusters Of Long Term Memory Genes, Julianna Bozler, Balint Z. Kacsoh, Hao Chen, William E. Theurkauf, Zhiping Weng, Giovanni Bosco 2017 Geisel School of Medicine at Dartmouth

A Systems Level Approach To Temporal Expression Dynamics In Drosophila Reveals Clusters Of Long Term Memory Genes, Julianna Bozler, Balint Z. Kacsoh, Hao Chen, William E. Theurkauf, Zhiping Weng, Giovanni Bosco

Program in Bioinformatics and Integrative Biology Publications and Presentations

The ability to integrate experiential information and recall it in the form of memory is observed in a wide range of taxa, and is a hallmark of highly derived nervous systems. Storage of past experiences is critical for adaptive behaviors that anticipate both adverse and positive environmental factors. The process of memory formation and consolidation involve many synchronized biological events including gene transcription, protein modification, and intracellular trafficking: However, many of these molecular mechanisms remain illusive. With Drosophila as a model system we use a nonassociative memory paradigm and a systems level approach to uncover novel transcriptional patterns. RNA sequencing ...


Modeling Virus Coinfection To Inform Management Of Maize Lethal Necrosis In Kenya, Frank H. Hilker, Linda S. J. Allen, Vrushali A. Bokil, Cheryl J. Briggs, Zhilan Feng, Karen A. Garrett, Louis J. Gross, Frédéric M. Hamelin, Michael J. Jeger, Carrie A. Manore, Alison G. Power, Margaret G. Redinbaugh, Megan A. Rúa, Nik J. Cunniffee 2017 Wright State University - Main Campus

Modeling Virus Coinfection To Inform Management Of Maize Lethal Necrosis In Kenya, Frank H. Hilker, Linda S. J. Allen, Vrushali A. Bokil, Cheryl J. Briggs, Zhilan Feng, Karen A. Garrett, Louis J. Gross, Frédéric M. Hamelin, Michael J. Jeger, Carrie A. Manore, Alison G. Power, Margaret G. Redinbaugh, Megan A. Rúa, Nik J. Cunniffee

Biological Sciences Faculty Publications

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large ...


Tthe Immature Stages And Natural History Of Antirrhea Adoptiva Porphyrosticta (Watkins, 1928) In Eastern Ecuador (Lepidoptera, Nymphalidae, Morphinae), Harold F. Greeney, Philip J. DeVries, Carla M. Penz, Rafael B. Granizo-T, Heidi Connahs, John O. Stireman III, Thomas R. Walla, Lee A. Dyer 2017 Wright State University - Main Campus

Tthe Immature Stages And Natural History Of Antirrhea Adoptiva Porphyrosticta (Watkins, 1928) In Eastern Ecuador (Lepidoptera, Nymphalidae, Morphinae), Harold F. Greeney, Philip J. Devries, Carla M. Penz, Rafael B. Granizo-T, Heidi Connahs, John O. Stireman Iii, Thomas R. Walla, Lee A. Dyer

John Stireman

Here we describe the immature stages and ecological associations of Antirrhea adoptiva porphyrosticta Watkins, 1928 (Lepidoptera:Nymphalidae:Morphinae). The cloud forest bamboo, Chusquea scandens Kunth (Bambusoidea: Poaceae), serves as the larval food plant for this butterfly in eastern Ecuador, the first hostplant record for Antirrhea outside the family Arecaceae. The larvae of A. adoptiva porphyrosticta are superficially similar to those of other Antirrhea species. We also provide observations on adult and larval behavior. Caterpillars of this butterfly species are parasitized by tachinid flies, as well as by Ichneumonidae and a newly described braconid wasp.


Species Richness And Host Associations Of Lepidoptera-Attacking Tachinidae In The Northeast Ecuadorian Andes, John O. Stireman III, Harold F. Greeney, Lee A. Dyer 2017 Wright State University - Main Campus

Species Richness And Host Associations Of Lepidoptera-Attacking Tachinidae In The Northeast Ecuadorian Andes, John O. Stireman Iii, Harold F. Greeney, Lee A. Dyer

John Stireman

Most of the unknown biological diversity of macro-organisms remaining to be discovered and described lies in the tropical regions of the world and consists primarily of insects. Those insects with parasitoid lifestyles constitute a significant portion of insect diversity, yet parasitoids are among the most poorly known of major insect guilds in the humid tropics. Here we describe and analyze the richness of one diverse taxon of parasitoids, flies in the family Tachinidae, reared from Lepidoptera as part of a biological survey of Lepidoptera and their parasitoids in one mid-elevation (2000 m) area in the northeast Ecuadorian Andes. One hundred ...


Habitat Eradication And Cropland Intensification May Reduce Parasitoid Diversity And Natural Pest Control Services In Annual Crop Fields, D. K. Letourneau, Sara G. Bothwell Allen, Robert R. Kula, Michael J. Sharkey, John O. Stireman III 2017 Wright State University - Main Campus

Habitat Eradication And Cropland Intensification May Reduce Parasitoid Diversity And Natural Pest Control Services In Annual Crop Fields, D. K. Letourneau, Sara G. Bothwell Allen, Robert R. Kula, Michael J. Sharkey, John O. Stireman Iii

John Stireman

California’s central coast differs from many agricultural areas in the U.S., which feature large tracts of monoculture production fields and relatively simple landscapes. Known as the nation’s salad bowl, and producing up to 90% of U.S. production of lettuces, broccoli and Brussels sprouts, this region is a mosaic of fresh vegetable fields, coastal meadow, chaparral shrubs, riparian and woodland habitat. We tested for relationships between the percent cover of crops, riparian and other natural landscape vegetation and the species richness of parasitic wasps and flies foraging in crops, such as broccoli, kale and cauliflower, and interpreted ...


First Definitive Fossil Of An Oestroid Fly (Diptera: Calyptratae: Oestroidea) And The Dating Of Oestroid Divergences, Pierfilippo Cerretti, John O. Stireman III, Thomas Pape, James E. O'Hara, Marco A. Marinho, Knut Rognes, David A. Grimaldi 2017 Wright State University - Main Campus

First Definitive Fossil Of An Oestroid Fly (Diptera: Calyptratae: Oestroidea) And The Dating Of Oestroid Divergences, Pierfilippo Cerretti, John O. Stireman Iii, Thomas Pape, James E. O'Hara, Marco A. Marinho, Knut Rognes, David A. Grimaldi

John Stireman

Calyptrate flies include about 22,000 extant species currently classified into Hippoboscoidea (tsetse, louse, and bat flies), the muscoid grade (house flies and relatives) and the Oestroidea (blow flies, bot flies, flesh flies, and relatives). Calyptrates are abundant in nearly all terrestrial ecosystems, often playing key roles as decomposers, parasites, parasitoids, vectors of pathogens, and pollinators. For oestroids, the most diverse group within calyptrates, definitive fossils have been lacking. The first unambiguous fossil of Oestroidea is described based on a specimen discovered in amber from the Dominican Republic. The specimen was identified through digital dissection by CT scans, which provided ...


Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang 2017 University of Massachusetts Medical School

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Program in Bioinformatics and Integrative Biology Publications and Presentations

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...


Progress Towards A Molecular Phylogeny Of Tachinidae, Year Two, Isaac S. Winkler, John O. Stireman III, John K. Moulton, Pierfilippo Cerretti, Jeremy D. Blaschke 2017 Wright State University - Main Campus

Progress Towards A Molecular Phylogeny Of Tachinidae, Year Two, Isaac S. Winkler, John O. Stireman Iii, John K. Moulton, Pierfilippo Cerretti, Jeremy D. Blaschke

John Stireman

We reported last year (Stireman et al. 2013) in The Tachinid Times on our collaborative project, funded by the U.S. National Science Foundation, to study the phylogeny of Tachinidae on a worldwide scale. Since that report, we have made some significant progress towards our goal of assembling a robust phylogenetic tree for Tachinidae. Notably, Cerretti et al. (in press) completed a phylogenetic study using 135 morphological characters from 180 tachinid genera. Results from this study largely reflect, with some interesting exceptions, what we are finding from preliminary analyses of our molecular data. Although sampling of taxa and genes for ...


To 'Die Hel' And Back. Expeditions Of The Phylogeny Of World Tachinidae Project. Part I: Western Cape, South Africa, Pierfilippo Cerretti, James E. O'Hara, John O. Stireman III, Isaac S. Winkler, Ashley H. Kirk-Spriggs 2017 Wright State University - Main Campus

To 'Die Hel' And Back. Expeditions Of The Phylogeny Of World Tachinidae Project. Part I: Western Cape, South Africa, Pierfilippo Cerretti, James E. O'Hara, John O. Stireman Iii, Isaac S. Winkler, Ashley H. Kirk-Spriggs

John Stireman

The “Phylogeny of World Tachinidae” project kicked off with an operational meeting in June 2012 at the Canadian National Collection of Insects (CNC) in Ottawa. Goals were discussed, work plans prepared, and of course the destinations and timing of major field expeditions were debated. During our three years of National Science Foundation funding we hope to gather fresh material for molecular analysis from all biogeographic regions of the world.


Phylogenetic Reconstruction Of Exoristinae Using Molecular Data: A Bayesian Re-Analysis, John O. Stireman III 2017 Wright State University - Main Campus

Phylogenetic Reconstruction Of Exoristinae Using Molecular Data: A Bayesian Re-Analysis, John O. Stireman Iii

John Stireman

A few years ago I published the results of a phylogenetic analysis of New World Exoristinae based on molecular data from two genes, 28S rDNA and Elongation Factor 1-alpha (Stireman 2002). In that study I employed parsimony, neighbor joining, and maximum likelihood inference methods to generate phylogenetic reconstructions, and explored a variety of weighting schemes and combinations of the sequence data (i.e. each gene separately and both together). The results of these analyses generally supported recent taxonomic hypotheses (e.g., Herting 1984; Wood 1987; O’Hara and Wood 2004). For example, Tachinidae and Exoristinae were reconstructed as monophyletic in ...


Progress Towards A Phylogeny Of World Tachinidae. Year 1, John O. Stireman III, James E. O'Hara, Michael C. Moulton, Pierfilippo Cerretti, Isaac S. Winkler 2017 Wright State University - Main Campus

Progress Towards A Phylogeny Of World Tachinidae. Year 1, John O. Stireman Iii, James E. O'Hara, Michael C. Moulton, Pierfilippo Cerretti, Isaac S. Winkler

John Stireman

D eveloping a structural phylogenetic framework for the family Tachinidae has been an interest of mine since I first started working on tachinids as a graduate student. It was then that I developed a new phylogenetic perspective with which to view the world, and many of the questions I wanted to ask of tachinids depended on some level of phylogenetic knowledge of them. I was surprised at the time that no one had attempted a broad quantitative phylogenetic analysis of the family, and a publication from my thesis work on the Exoristinae (Stireman 2002) became the first such study that ...


Tachinid Collecting In Temperate South America. Expeditions Of The Phylogeny Of World Tachinide Project. Part Iii. Chile, John O. Stireman III, James E. O'Hara, Pierfilippo Cerretti, Diego J. Inclán 2017 Wright State University - Main Campus

Tachinid Collecting In Temperate South America. Expeditions Of The Phylogeny Of World Tachinide Project. Part Iii. Chile, John O. Stireman Iii, James E. O'Hara, Pierfilippo Cerretti, Diego J. Inclán

John Stireman

As readers of this newsletter are likely familiar, we and our collaborators have been working for the past several years on a family-wide phylogeny of the Tachinidae of the world (see Stireman et al. 2013, Winkler et al. 2014). We have already published a morphological analysis of tachinid phylogenetics (Cerretti et al. 2014), as well as an initial molecular phylogenetic framework for the family (Winkler et al. 2015). An in-depth molecular phylogenetic analysis of the Phasiinae led by Jeremy Blaschke (originally at University of Tennessee and now at Union University, TN) and Kevin Moulton (U. of Tenn.) is currently being ...


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