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Conversion Of An Instantaneous Activating K+ Channel Into A Slow Activating Inward Rectifier, Dirk Baumeister, Brigitte Hertel, Indra Schroeder, Sabrina Gazzarrini, Stefan M. Kast, James L. Van Etten, Anna Moroni, Gerhard Thiel 2017 Technische Universität Darmstadt

Conversion Of An Instantaneous Activating K+ Channel Into A Slow Activating Inward Rectifier, Dirk Baumeister, Brigitte Hertel, Indra Schroeder, Sabrina Gazzarrini, Stefan M. Kast, James L. Van Etten, Anna Moroni, Gerhard Thiel

James Van Etten Publications

The miniature channel, Kcv, is a structural equivalent of the pore of all K+ channels. Here, we follow up on a previous observation that a largely voltage-insensitive channel can be converted into a slow activating inward rectifier after extending the outer transmembrane domain by one Ala. This gain of rectification can be rationalized by dynamic salt bridges at the cytosolic entrance to the channel; opening is favored by voltage-sensitive formation of salt bridges and counteracted by their disruption. Such latent voltage sensitivity in the pore could be relevant for the understanding of voltage gating in complex Kv channels.


Structure Of The Chlorovirus Pbcv-1 Major Capsid Glycoprotein Determined By Combining Crystallographic And Carbohydrate Molecular Modeling Approaches, Cristina De Castro, Thomas Klose, Immacolata Speciale, Rosa Lanzetta, Antonio Molinaro, James L. Van Etten, Michael G. Rossmann 2017 University of Napoli

Structure Of The Chlorovirus Pbcv-1 Major Capsid Glycoprotein Determined By Combining Crystallographic And Carbohydrate Molecular Modeling Approaches, Cristina De Castro, Thomas Klose, Immacolata Speciale, Rosa Lanzetta, Antonio Molinaro, James L. Van Etten, Michael G. Rossmann

James Van Etten Publications

The glycans of the major capsid protein (Vp54) of Paramecium bursaria chlorella virus (PBCV-1) were recently described and found to be unusual. This prompted a reexamination of the previously reported Vp54 X-ray structure. A detailed description of the complete glycoprotein was achieved by combining crystallographic data with molecular modeling. The crystallographic data identified most of the monosaccharides located close to the protein backbone, but failed to detect those further from the glycosylation sites. Molecular modeling complemented this model by adding the missing monosaccharides and examined the conformational preference of the whole molecule, alone or within the crystallographic environment. Thus, combining …


Climate Change And The Integrity Of Science, Peter H. Gleick, James L. Van Etten, Members of the U.S. National Academy of Sciences 2016 Pacific Institute

Climate Change And The Integrity Of Science, Peter H. Gleick, James L. Van Etten, Members Of The U.S. National Academy Of Sciences

James Van Etten Publications

We are deeply disturbed by the recent escalation of political assaults on scientists in general and on climate scientists in particular. All citizens should understand some basic scientific facts. There is always some uncertainty associated with scientific conclusions; science never absolutely proves anything. When someone says that society should wait until scientists are absolutely certain before taking any action, it is the same as saying society should never take action. For a problem as potentially catastrophic as climate change, taking no action poses a dangerous risk for our planet.

Scientific conclusions derive from an understanding of basic laws supported by …


Predators Catalyze An Increase In Chloroviruses By Foraging On The Symbiotic Hosts Of Zoochlorellae, John DeLong, Zeina Al-Ameeli, Garry A. Duncan, James L. Van Etten, David D. Dunigan Ph. D. 2016 University of Nebraska-Lincoln

Predators Catalyze An Increase In Chloroviruses By Foraging On The Symbiotic Hosts Of Zoochlorellae, John Delong, Zeina Al-Ameeli, Garry A. Duncan, James L. Van Etten, David D. Dunigan Ph. D.

James Van Etten Publications

Virus population growth depends on contacts between viruses and their hosts. It is often unclear how sufficient contacts are made between viruses and their specific hosts to generate spikes in viral abundance. Here, we show that copepods, acting as predators, can bring aquatic viruses and their algal hosts into contact. Specifically, predation of the protist Paramecium bursaria by copepods resulted in a >100-fold increase in the number of chloroviruses in 1 d. Copepod predation can be seen as an ecological “catalyst” by increasing contacts between chloroviruses and their hosts, zoochlorellae (endosymbiotic algae that live within paramecia), thereby facilitating viral population …


Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby 2016 Colorado State University

Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby

Publications and Research

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic …


Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, KHM Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman 2016 Bangladesh Agricultural University

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …


A Pan-Dengue Virus Reverse Transcription-Insulated Isothermal Pcr Assay Intended For Point-Of-Need Diagnosis Of Dengue Virus Infection By Use Of The Pockit Nucleic Acid Analyzer, Yun Young Go, R. P. V. Jayanthe Rajapakse, Senanayake A. M. Kularatne, Pei-Yu Alison Lee, Keun Bon Ku, Sangwoo Nam, Pin-Hsing Chou, Yun-Long Tsai, Yu-Lun Liu, Hsiao-Fen Grace Chang, Hwa-Tang Thomas Wang, Udeni B. R. Balasuriya 2016 Korea Research Institute of Chemical Technology, South Korea

A Pan-Dengue Virus Reverse Transcription-Insulated Isothermal Pcr Assay Intended For Point-Of-Need Diagnosis Of Dengue Virus Infection By Use Of The Pockit Nucleic Acid Analyzer, Yun Young Go, R. P. V. Jayanthe Rajapakse, Senanayake A. M. Kularatne, Pei-Yu Alison Lee, Keun Bon Ku, Sangwoo Nam, Pin-Hsing Chou, Yun-Long Tsai, Yu-Lun Liu, Hsiao-Fen Grace Chang, Hwa-Tang Thomas Wang, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Dengue virus (DENV) infection is considered a major public health problem in developing tropical countries where the virus is endemic and continues to cause major disease outbreaks every year. Here, we describe the development of a novel, inexpensive, and user-friendly diagnostic assay based on a reverse transcription-insulated isothermal PCR (RT-iiPCR) method for the detection of all four serotypes of DENV in clinical samples. The diagnostic performance of the newly established pan-DENV RT-iiPCR assay targeting a conserved 3′ untranslated region of the viral genome was evaluated. The limit of detection with a 95% confidence was estimated to be 10 copies of …


Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard 2016 University of Tennessee Health Science Center

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard

Theses and Dissertations (ETD)

A novel orthomyxovirus was recently identified from pigs, with subsequent work suggesting the natural reservoir being bovine populations. The virus had genome characteristics most similar to influenza C viruses (ICV) but, due to the extent of sequence divergence, was proposed as a new genus, influenza D virus (IDV). Current literature on IDV has largely focused on the agricultural significance of the virus and provided evidence for the agricultural impact via observation of widespread prevalence and pathology in laboratory infected cattle. However, only one study, which identified 1.3% seroprevalence in a small cohort, has addressed the zoonotic potential of IDV to …


Bacteriophages: The Answer To Antibiotic Resistance?, Allie Casto, Adam Hurwitz, Kunny Kou, Gregory Mansour, Allison Mayzel, Rachel Policke, Alexander Schmidt, Rowan Shartel, Olivia Smith, Augustus Snyder, Allison Woolf 2016 James Madison University

Bacteriophages: The Answer To Antibiotic Resistance?, Allie Casto, Adam Hurwitz, Kunny Kou, Gregory Mansour, Allison Mayzel, Rachel Policke, Alexander Schmidt, Rowan Shartel, Olivia Smith, Augustus Snyder, Allison Woolf

James Madison Undergraduate Research Journal (JMURJ)

Bacteriophages, viruses that infect bacteria, have numerous applications in the medical, agricultural, and research fields, especially as an alternative to antibiotics in the age of antibiotic resistance. Phages are able to lyse, or break apart, bacterial cells with fewer side effects, more specificity, and less likelihood of resistance than antibiotics. The acceptance of phages in medicine and agriculture around the world today is not universal, and the United States Food and Drug Administration (FDA) has been slow to recognize phage therapy as a legitimate treatment. However, the successful use of phages in the past, as well as promising trial results …


Three-Year Survey Of Abundance, Prevalence And Genetic Diversity Of Chlorovirus Populations In A Small Urban Lake, Cristian F. Quispe, Olivia Sonderman, Anya Seng, Brenna Rasmussen, Garrett Weber, Claire Mueller, David Dunigan, James L. Van Etten 2016 University of Nebraska-Lincoln

Three-Year Survey Of Abundance, Prevalence And Genetic Diversity Of Chlorovirus Populations In A Small Urban Lake, Cristian F. Quispe, Olivia Sonderman, Anya Seng, Brenna Rasmussen, Garrett Weber, Claire Mueller, David Dunigan, James L. Van Etten

James Van Etten Publications

Inland water environments cover about 2.5 percent of our planet and harbor huge numbers of known and still unknown microorganisms. In this report, we examined water samples for the abundance, prevalence, and genetic diversity of a group of infectious viruses (chloroviruses) that infect symbiotic chlorella-like green algae. Samples were collected on a weekly basis for a period of 24 to 36 months from a recreational freshwater lake in Lincoln, Nebraska, and assayed for infectious viruses by plaque assay. The numbers of infectious virus particles were both host- and site-dependent. The consistent fluctuations in numbers of viruses suggest their impact as …


Cell-Free And Cell-Based Approaches To Explore The Roles Of Host Membranes And Lipids In The Formation Of Viral Replication Compartment Induced By Tombusviruses, Peter D. Nagy, Judit Pogany, Kai Xu 2016 University of Kentucky

Cell-Free And Cell-Based Approaches To Explore The Roles Of Host Membranes And Lipids In The Formation Of Viral Replication Compartment Induced By Tombusviruses, Peter D. Nagy, Judit Pogany, Kai Xu

Plant Pathology Faculty Publications

Plant positive strand RNA viruses are intracellular infectious agents that take advantage of cellular lipids and membranes to support replication and protect viral RNA from degradation by host antiviral responses. In this review, we discuss how Tomato bushy stunt virus (TBSV) co-opts lipid transfer proteins and modulates lipid metabolism and transport to facilitate the assembly of the membrane-bound viral replicase complexes within intricate replication compartments. Identification and characterization of the proviral roles of specific lipids and proteins involved in lipid metabolism based on results from yeast (Saccharomyces cerevisiae) model host and cell-free approaches are discussed. The review also …


Virus–Host Interactions: Insights From The Replication Cycle Of The Large Paramecium Bursaria Chlorella Virus, Elad Milrot, Yael Mutsafi, Yael Fridmann-Sirkis, Eyal Shimoni, Katya Rechav, James Gurnon, James L. Van Etten, Abraham Minsky 2016 The Weizmann Institute of Science, Rehovot, Israel

Virus–Host Interactions: Insights From The Replication Cycle Of The Large Paramecium Bursaria Chlorella Virus, Elad Milrot, Yael Mutsafi, Yael Fridmann-Sirkis, Eyal Shimoni, Katya Rechav, James Gurnon, James L. Van Etten, Abraham Minsky

James Van Etten Publications

The increasing interest in cytoplasmic factories generated by eukaryotic-infecting viruses stems from the realization that these highly ordered assemblies may contribute fundamental novel insights to the functional significance of order in cellular biology. Here, we report the formation process and structural features of the cytoplasmic factories of the large dsDNA virus Paramecium bursaria chlorella virus 1 (PBCV-1). By combining diverse imaging techniques, including scanning transmission electron microscopy tomography and focused ion beam technologies, we show that the architecture and mode of formation of PBCV-1 factories are significantly different from those generated by their evolutionary relatives Vaccinia and Mimivirus. Specifically, PBCV-1 …


Chloroviruses N-Linked Glycans Share A New Type Of Conserved Core Architecture Unprecedented In Any Form Of Life / [Published As] N-Linked Glycans Of Chloroviruses Sharing A Core Architecture Without Precedent, Cristina De Castro, Immacolata Speciale, Garry Duncan, David Dunigan, Irina Agarkova, Rosa Lanzetta, Luisa Sturiale, Angelo Palmigiano, Domenico Garozzo, Antonio Molinaro, Michela Tonetti, James L. Van Etten 2016 University of Napoli

Chloroviruses N-Linked Glycans Share A New Type Of Conserved Core Architecture Unprecedented In Any Form Of Life / [Published As] N-Linked Glycans Of Chloroviruses Sharing A Core Architecture Without Precedent, Cristina De Castro, Immacolata Speciale, Garry Duncan, David Dunigan, Irina Agarkova, Rosa Lanzetta, Luisa Sturiale, Angelo Palmigiano, Domenico Garozzo, Antonio Molinaro, Michela Tonetti, James L. Van Etten

James Van Etten Publications

N-glycosylation is a fundamental modification of proteins that exists in the three domains of life and in some viruses, including the chloroviruses, for which a new type of core N-glycan is described. This N-glycan core structure common to all chloroviruses is a pentasaccharide with a β-glucose linked to an asparagine residue that is not located in the typical sequon N-X-T/S. The glucose is linked to a terminal xylose unit and a hyperbranched fucose, in turn substituted with a terminal galactose and a second xylose residue. The third position of the fucose unit is always linked to a rhamnose, which is …


The Impact Of Urbanization On Mosquito-Borne Viruses, Nikhita Puthuveetil 2016 Virginia Commonwealth University

The Impact Of Urbanization On Mosquito-Borne Viruses, Nikhita Puthuveetil

Undergraduate Research Posters

Mosquito-borne diseases such as yellow fever, dengue, and West Nile are rapidly emerging across the globe. Their emergence is often aided by the growth of their vector population, or the organisms that transmit the virus to the host. Urbanization and land use often destroys the habitat of the virus and its vector. However, the virus and its vector often survive despite the changes to its environment. The goal of this paper is to find out exactly how urbanization and changes in land use affect mosquito-borne viruses and how these viruses survive despite the destruction of their habitats. To understand how …


Zika Virus- Emergence, Evolution, Pathology, Diagnosis, And Control: Current Global Scenario And Future Perspectives- A Comprehensive Review, Raj K. Singh, Kuldeep Dhama, Yashpal S. Malik, Muthannan A. Ramakrishnan, Kumaragurubaran Karthik, Sunil K. Joshi 2016 Old Dominion University

Zika Virus- Emergence, Evolution, Pathology, Diagnosis, And Control: Current Global Scenario And Future Perspectives- A Comprehensive Review, Raj K. Singh, Kuldeep Dhama, Yashpal S. Malik, Muthannan A. Ramakrishnan, Kumaragurubaran Karthik, Sunil K. Joshi

Bioelectrics Publications

This review converses the Zika virus which has attained global concern due to its rapid pandemic potential and impact on humans. Though Zika virus was first isolated in 1947, till the recent large-scale outbreak which occurred in Micronesia, in 2007, the virus was placed into the innocuous pathogen category. The World Health Organization on 1 February 2016 declared it as a Public Health Emergency of International Concern.' Of the note, American as well as Pacific Island strains/isolates is relatively closer to Asian lineage strains. The African and American strains share more than 87.5% and 95% homologies with Asian strains/isolates, respectively. …


The Differentiation And Protective Function Of Cytolytic Cd4 T Cells In Influenza Infection, Deborah M. Brown, Anna T. Lampe, Aspen M. Workman 2016 University of Nebraska-Lincoln

The Differentiation And Protective Function Of Cytolytic Cd4 T Cells In Influenza Infection, Deborah M. Brown, Anna T. Lampe, Aspen M. Workman

Faculty Publications in the Biological Sciences

CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein–Barr virus, and influenza among others. We now appreciate …


Expansion Of The Chlorovirus Genus By Studies On Virus Natural History And Chlorella Host Metabolism, Cristian F. Quispe 2015 University of Nebraska-Lincoln

Expansion Of The Chlorovirus Genus By Studies On Virus Natural History And Chlorella Host Metabolism, Cristian F. Quispe

Dissertations and Theses in Biological Sciences

Inland waters cover about 2.5 percent of our planet and harbor huge numbers of known and unknown microorganisms including viruses. Viruses likely play dynamic, albeit largely undocumented roles in regulating microbial communities and in recycling nutrients in the ecosystem. Phycodnaviruses are a genetically diverse, yet morphologically similar, group of large dsDNA-containing viruses (160- to 560-kb) that inhabit aquatic environments. Members of the genus Chlorovirus are common in freshwater. They replicate in eukaryotic, single-celled, chlorella-like green algae that normally exist as endosymbionts of protists in nature. Very little is known about the natural history of the chloroviruses and how they achieve …


The Spatial Dynamics Of Dengue Virus In Kamphaeng Phet, Thailand, Piraya Bhoomiboonchoo, Robert V. Gibbons, Angkana Huang, In-Kyu Yoon, Darunee Buddhari, Ananda Nisalak, Natkamol Chansatiporn, Mathuros Thipayamongkolgul, Siripen Kalanarooj, Timothy Endy, Alan L. Rothman, Anon Srikiatkhachorn, Sharone Green, Mammen P. Mammen, Derek A. Cummings, Henrik Salje 2015 Mahidol University

The Spatial Dynamics Of Dengue Virus In Kamphaeng Phet, Thailand, Piraya Bhoomiboonchoo, Robert V. Gibbons, Angkana Huang, In-Kyu Yoon, Darunee Buddhari, Ananda Nisalak, Natkamol Chansatiporn, Mathuros Thipayamongkolgul, Siripen Kalanarooj, Timothy Endy, Alan L. Rothman, Anon Srikiatkhachorn, Sharone Green, Mammen P. Mammen, Derek A. Cummings, Henrik Salje

Sharone Green

BACKGROUND: Dengue is endemic to the rural province of Kamphaeng Phet, Northern Thailand. A decade of prospective cohort studies has provided important insights into the dengue viruses and their generated disease. However, as elsewhere, spatial dynamics of the pathogen remain poorly understood. In particular, the spatial scale of transmission and the scale of clustering are poorly characterized. This information is critical for effective deployment of spatially targeted interventions and for understanding the mechanisms that drive the dispersal of the virus.

METHODOLOGY/PRINCIPAL FINDINGS: We geocoded the home locations of 4,768 confirmed dengue cases admitted to the main hospital in Kamphaeng Phet …


Identification Of The Staphylococcal Cassette Chromosome Mec (Sccmec) Element In Viral Fractions From Environmental Samples, Emily M. Pelto 2015 James Madison University

Identification Of The Staphylococcal Cassette Chromosome Mec (Sccmec) Element In Viral Fractions From Environmental Samples, Emily M. Pelto

Senior Honors Projects, 2010-2019

Antibiotic resistance attributed to methicillin-resistant Staphylococcus aureus (MRSA) has become a growing concern over the last decade in both the healthcare and agricultural environment. This resistance is encoded by the gene mecA that is located on a mosaic, mobile genetic element called the Staphylococcal Cassette Chromosome mec (SCCmec) element. It is proposed that the transfer of the SCCmec element and resulting spread of resistance occur by transduction, the transfer of genetic material from bacterium to bacterium by a bacteriophage. Specifically, it is hypothesized that the transduction of this resistance is occurring in the agricultural setting. To test …


Engineering Of A Light-Gated Potassium Channel, Christian Cosentino, Laura Alberio, Sabrina Gazzarrini, Marco Aquila, Eduardo Romano, Solei Cermenati, Paolo Zuccolini, Jan Petersen, Monica Beltrame, James L. Van Etten, John M. Christie, Gerhard Thiel, Anna Moroni 2015 Universita degli Studi di Milano

Engineering Of A Light-Gated Potassium Channel, Christian Cosentino, Laura Alberio, Sabrina Gazzarrini, Marco Aquila, Eduardo Romano, Solei Cermenati, Paolo Zuccolini, Jan Petersen, Monica Beltrame, James L. Van Etten, John M. Christie, Gerhard Thiel, Anna Moroni

James Van Etten Publications

The present palette of opsin-based optogenetic tools lacks a light-gated potassium (K+) channel desirable for silencing of excitable cells. Here, we describe the construction of a blue-light–induced K+ channel 1 (BLINK1) engineered by fusing the plant LOV2-Ja photosensory module to the small viral K+ channel Kcv. BLINK1 exhibits biophysical features of Kcv, including K+ selectivity and high single-channel conductance, but reversibly photoactivates in blue light. Opening of BLINK1 channels hyperpolarizes the cell to the K+ equilibrium potential. Ectopic expression of BLINK1 reversibly inhibits the escape response in light-exposed zebrafish larvae. BLINK1 therefore provides a single-component optogenetic tool that can establish …


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