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Sample records for capocaccia manuela merli

  1. MER SPICE Interface

    NASA Technical Reports Server (NTRS)

    Sayfi, Elias

    2004-01-01

    MER SPICE Interface is a software module for use in conjunction with the Mars Exploration Rover (MER) mission and the SPICE software system of the Navigation and Ancillary Information Facility (NAIF) at NASA's Jet Propulsion Laboratory. (SPICE is used to acquire, record, and disseminate engineering, navigational, and other ancillary data describing circumstances under which data were acquired by spaceborne scientific instruments.) Given a Spacecraft Clock value, MER SPICE Interface extracts MER-specific data from SPICE kernels (essentially, raw data files) and calculates values for Planet Day Number, Local Solar Longitude, Local Solar Elevation, Local Solar Azimuth, and Local Solar Time (UTC). MER SPICE Interface was adapted from a subroutine, denoted m98SpiceIF written by Payam Zamani, that was intended to calculate SPICE values for the Mars Polar Lander. The main difference between MER SPICE Interface and m98SpiceIf is that MER SPICE Interface does not explicitly call CHRONOS, a time-conversion program that is part of a library of utility subprograms within SPICE. Instead, MER SPICE Interface mimics some portions of the CHRONOS code, the advantage being that it executes much faster and can efficiently be called from a pipeline of events in a parallel processing environment.

  2. Alone You Are Nobody, Together We Float: The Manuela Ramos Movement. Quality/Calidad/Qualite Number 10.

    ERIC Educational Resources Information Center

    Rogow, Debbie

    The Manuela Ramos Movement began in the 1970s when seven women in Lima, Peru, started meeting each Tuesday to reconsider their assumptions about everyday life. By 1980, the group formed a nongovernmental organization whose strategy was to train women community leaders in Lima's barrios through workshops focusing on the following themes: identity…

  3. Learning Cultures in Travel and Tourism: A Critique of Manuela du Bois-Reymond's Trendsetter Learner Thesis

    ERIC Educational Resources Information Center

    Morrison, Andrew

    2011-01-01

    This article aims to contribute to the discussion surrounding Manuela du Bois-Reymond's important "trendsetter learner" thesis and, in so doing, to join the wider debate about post-compulsory learning cultures. The article outlines the trendsetter learner thesis and then considers recent criticisms that it has attracted. While the author concurs…

  4. Middle East Respiratory Syndrome (MERS)

    MedlinePlus

    Middle East Respiratory Syndrome Coronavirus; MERS-CoV; Novel coronavirus; nCoV ... Centers for Disease Control and Prevention. Middle East ... 2, 2015. www.cdc.gov/coronavirus/mers/faq.html . Accessed April ...

  5. MER Telemetry Processor

    NASA Technical Reports Server (NTRS)

    Lee, Hyun H.

    2012-01-01

    MERTELEMPROC processes telemetered data in data product format and generates Experiment Data Records (EDRs) for many instruments (HAZCAM, NAVCAM, PANCAM, microscopic imager, Moessbauer spectrometer, APXS, RAT, and EDLCAM) on the Mars Exploration Rover (MER). If the data is compressed, then MERTELEMPROC decompresses the data with an appropriate decompression algorithm. There are two compression algorithms (ICER and LOCO) used in MER. This program fulfills a MER specific need to generate Level 1 products within a 60-second time requirement. EDRs generated by this program are used by merinverter, marscahv, marsrad, and marsjplstereo to generate higher-level products for the mission operations. MERTELEPROC was the first GDS program to process the data product. Metadata of the data product is in XML format. The software allows user-configurable input parameters, per-product processing (not streambased processing), and fail-over is allowed if the leading image header is corrupted. It is used within the MER automated pipeline. MERTELEMPROC is part of the OPGS (Operational Product Generation Subsystem) automated pipeline, which analyzes images returned by in situ spacecraft and creates level 1 products to assist in operations, science, and outreach.

  6. MER ARA pyroshock test results

    NASA Technical Reports Server (NTRS)

    Chang, Kurng Y.

    2004-01-01

    This paper presents the shock test results achieved in the MER ARA/brush motor pyroshock qualification. The results of MER flight system pyrofiring tests in comparison with the ARA shock test requirements are discussed herein. Alternate test methods were developed in an effort to qualify the critical MER equipment for adequate performance in the actual flight pyroshock condition.

  7. Analyzing MER Uplink Reports

    NASA Technical Reports Server (NTRS)

    Savin, Stephen C.

    2005-01-01

    The MER project includes two rovers working simultaneously on opposite sides of Mars each receiving commands only once a day. Creating this uplink is critical, since a failed uplink means a lost day and a waste of money. Examining the process of creating this uplink, I tracked the use of the system developed for requesting observations as well as the development, from stage to stage, in forming an activity plan. I found the system for requesting observations was commonly misused, if used at all. There are half a dozen reports to document the creation of the uplink plan and often there are discrepancies among them. Despite this, the uplink process worked very well and MER has been one of the most successful missions for NASA in recent memory. Still it is clear there is room for improvement.

  8. Middle East respiratory syndrome (MERS)

    PubMed Central

    Cunha, Cheston B; Opal, Steven M

    2014-01-01

    Coronaviruses have traditionally been associated with mild upper respiratory tract infections throughout the world. In the fall of 2002, a new coronavirus emerged in in Asia causing severe viral pneumonia, i.e., severe acute respiratory syndrome (SARS). Nearly a decade following the SARS epidemic, a new coronavirus causing severe viral pneumonia has emerged, i.e., middle east respiratory syndrome (MERS). Since the initial case of MERS-CoV occurred in June of 2012 in Saudi Arabia there have been 688 confirmed cases and 282 deaths in 20 countries.   Although both SARS and MERS are caused by coronaviruses, SARS was characterized by efficient human transmission and relatively low mortality rate. In contrast, MERS is relatively inefficiently transmitted to humans but has a high mortality rate. Given the potential overlap in presentation and manifestation, it is important to understand the clinical and epidemiologic differences between MERS, SARS and influenza. PMID:25089913

  9. Middle East Respiratory Syndrome (MERS)

    MedlinePlus

    ... United Kingdom (UK), and United States of America (USA). CDC Commentary: Be on the Lookout for MERS- ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  10. First record of Loricifera from the Iberian Peninsula, with the description of Rugiloricus manuelae sp. nov., (Loricifera, Pliciloricidae)

    NASA Astrophysics Data System (ADS)

    Pardos, Fernando; Kristensen, Reinhardt Møbjerg

    2013-12-01

    Sediment samples were taken along the Cantabric platform (Northern Spain) from 200 to 600 meters depth in October 1990. Forty specimens of loriciferans were sorted out of the samples, of which 38 specimens belong to a new species of Rugiloricus. The new species, R. manuelae sp. nov., was investigated with both light (DIC) and electron microscopy (SEM). Complete descriptions of both adult and larval stages are provided, including mapping of the introvert scalids for both stages. Information from a molting stage with an adult male inside confirms conspecificity of larvae and adults. The presence of a highly reduced postlarval stage leaded to the suggestion of a new modified life cycle for the family Pliciloricidae.

  11. Middle East Respiratory Syndrome (MERS).

    PubMed

    Rasmussen, Sonja A; Watson, Amelia K; Swerdlow, David L

    2016-06-01

    Since the identification of the first patients with Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, over 1,600 cases have been reported as of February 2016. Most cases have occurred in Saudi Arabia or in other countries on or near the Arabian Peninsula, but travel-associated cases have also been seen in countries outside the Arabian Peninsula. MERS-CoV causes a severe respiratory illness in many patients, with a case fatality rate as high as 40%, although when contacts are investigated, a significant proportion of patients are asymptomatic or only have mild symptoms. At this time, no vaccines or treatments are available. Epidemiological and other data suggest that the source of most primary cases is exposure to camels. Person-to-person transmission occurs in household and health care settings, although sustained and efficient person-to-person transmission has not been observed. Strict adherence to infection control recommendations has been associated with control of previous outbreaks. Vigilance is needed because genomic changes in MERS-CoV could result in increased transmissibility, similar to what was seen in severe acute respiratory syndrome coronavirus (SARS-CoV). PMID:27337460

  12. Robust k-mer frequency estimation using gapped k-mers

    PubMed Central

    Ghandi, Mahmoud; Mohammad-Noori, Morteza

    2013-01-01

    Oligomers of fixed length, k, commonly known as k-mers, are often used as fundamental elements in the description of DNA sequence features of diverse biological function, or as intermediate elements in the constuction of more complex descriptors of sequence features such as position weight matrices. k-mers are very useful as general sequence features because they constitute a complete and unbiased feature set, and do not require parameterization based on incomplete knowledge of biological mechanisms. However, a fundamental limitation in the use of k-mers as sequence features is that as k is increased, larger spatial correlations in DNA sequence elements can be described, but the frequency of observing any specific k-mer becomes very small, and rapidly approaches a sparse matrix of binary counts. Thus any statistical learning approach using k-mers will be susceptible to noisy estimation of k-mer frequencies once k becomes large. Because all molecular DNA interactions have limited spatial extent, gapped k-mers often carry the relevant biological signal. Here we use gapped k-mer counts to more robustly estimate the ungapped k-mer frequencies, by deriving an equation for the minimum norm estimate of k-mer frequencies given an observed set of gapped k-mer frequencies. We demonstrate that this approach provides a more accurate estimate of the k-mer frequencies in real biological sequences using a sample of CTCF binding sites in the human genome. PMID:23861010

  13. Exploring Gusev with MER A

    NASA Astrophysics Data System (ADS)

    Grin, E. A.; Cabrol, N. A.; Des Marais, D.; Farmer, J.; Greeley, R.; Carr, M.; Kramer, M.; Moore, J.; Sutter, B.; Fike, D.; Kuzmin, R.; Grant, F.; Barlow, N.; Newsom, H.; Tanaka, K.; Urquhart, M.; de Goursac, O.; Grisby, B.

    2002-12-01

    Gusev will be an outstanding candidate to achieve the 2003 MER mission goals. The crater has collected sediments from a diversity of parent rocks in the vast Maadim Vallis watershed over a period of three billion years. Because of the interaction between Gusev and Maadim, it has been proposed that a significant volume of the sedimentary material in the crater is of aqueous origin. Mars Odyssey has shown that the hydrogen abundance in the Gusev region is higher than average at corresponding latitudes. This observation could be consistent with a past long lived aqueous activity. The presence of aqueous material is central to the MER mission because it can provide clues about the past water history, climate changes, and the potential habitability of Mars. However, while Gusev is recognized as a primary site because of its past fluvio lacustrine activity, the geological diversity and history of its immediate surroundings makes it exceptional and provides the foundation for an exciting exploration leading to key discoveries. In addition to aqueous, many other processes can have contributed to the material in the crater basin: volcanic, Apollinaris patera is only 200 km away, aeolian, glacial, and global airfall processes. How to identify the signature of each process? What was their succession in time? Do we see the evolution from perennial to more episodic lakes? Do we see interaction between volcanic, glacial, aeolian and lacustrine processes? What was the recurrence of dry episodes? What type of measurements can provide a definitive answer for each of these questions in the 600 m traverse range that the rover will accomplish? What diversity can we also expect in this range? Finally, the uniqueness and potential of Gusev does not reside only in this exceptional diversity. As there is evidence for long lived lake episodes, Gusev also offers the unique possibility to study for the first time the results of the in situ formation of aqueous sediments and minerals in their

  14. Travelers' Health: MERS in the Arabian Peninsula

    MedlinePlus

    ... Zika risk at high elevations Find a Clinic Yellow Fever Vaccinations Clinics FAQ Disease Directory Resources Resources for ... ... found in people. Symptoms of MERS include fever, cough, and shortness of breath. CDC is working ...

  15. Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27

    PubMed Central

    Yu, Xiaojuan; Zhang, Senyan; Jiang, Liwei; Cui, Ye; Li, Dongxia; Wang, Dongli; Wang, Nianshuang; Fu, Lili; Shi, Xuanlin; Li, Ziqiang; Zhang, Linqi; Wang, Xinquan

    2015-01-01

    The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection. PMID:26281793

  16. Potential MER Landing Site in Melas Chasma

    NASA Technical Reports Server (NTRS)

    Weitz, C. M.; Parker, Timothy J.; Anderson, F. Scott

    2001-01-01

    We have selected one area in Valles Marineris as a potential landing site for the Mars Exploration Rover (MER) mission. After 30 years of analyses, the formation of the Valles Marineris system of troughs and its associated deposits still remains an enigma. Understanding all aspects of the Valles Marineris would significantly contribute to deciphering the internal and external history of Mars. A landing site within Melas Chasma could provide insight into both the formation of Valles Marineris and the composition and origin of the interior layered deposits (ILDs). The ILDs have been proposed as: (1) sedimentary deposits formed in lakes mass wasted material from the walls; (3) remnants of the wall rock; (4) carbonate deposits; (5) aeolian deposits; and (6) volcanic. More recently, Malin and Edgett suggest that the fine-scale, rhythmic layering seen in the interior deposits, as well as other layered deposits in craters, supports a sedimentary origin. Because an understanding of the formation of Valles Marineris and its interior deposits is so important to deciphering the history of Mars, we have proposed a landing site for the MER mission on an exposure of interior deposits in western Melas Chasma. Either MER-A and MER-B could land at this same location.

  17. Targeting Axl and Mer kinases in cancer.

    PubMed

    Verma, Anupam; Warner, Steven L; Vankayalapati, Hariprasad; Bearss, David J; Sharma, Sunil

    2011-10-01

    Receptor tyrosine kinases (RTK) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play an important role in signal transduction in both normal and malignant cells. The mammalian TAM RTK family includes 3 closely related members: Tyro-3, Axl, and Mer. Overexpression or ectopic expression of the TAM receptors has been detected in a wide array of human cancers. Growth arrest-specific gene 6 has been identified as the major ligand for these TAM RTKs, and its binding to the receptors has been shown to promote proliferation and survival of cancer cells in vitro. Abnormal expression and activation of Axl or Mer can provide a survival advantage for certain cancer cells. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. This review elucidates the role of Axl and Mer in normal cellular function and their role in oncogenesis. In addition, we review the potential to inhibit these RTKs for the development of therapeutic targets in treatment of cancer. PMID:21933973

  18. The MER/CIP Portal for Ground Operations

    NASA Technical Reports Server (NTRS)

    Chan, Louise; Desai, Sanjay; DOrtenzio, Matthew; Filman, Robtert E.; Heher, Dennis M.; Hubbard, Kim; Johan, Sandra; Keely, Leslie; Magapu, Vish; Mak, Ronald

    2003-01-01

    We developed the Mars Exploration Rover/Collaborative Information Portal (MER/CIP) to facilitate MER operations. MER/CIP provides a centralized, one-stop delivery platform integrating science and engineering data from several distributed heterogeneous data sources. Key issues for MER/CIP include: 1) Scheduling and schedule reminders; 2) Tracking the status of daily predicted outputs; 3) Finding and analyzing data products; 4) Collaboration; 5) Announcements; 6) Personalization.

  19. Human Centered Design and Development for NASA's MerBoard

    NASA Technical Reports Server (NTRS)

    Trimble, Jay

    2003-01-01

    This viewgraph presentation provides an overview of the design and development process for NASA's MerBoard. These devices are large interactive display screens which can be shown on the user's computer, which will allow scientists in many locations to interpret and evaluate mission data in real-time. These tools are scheduled to be used during the 2003 Mars Exploration Rover (MER) expeditions. Topics covered include: mission overview, Mer Human Centered Computers, FIDO 2001 observations and MerBoard prototypes.

  20. Animal models for SARS and MERS coronaviruses

    PubMed Central

    Gretebeck, Lisa M; Subbarao, Kanta

    2015-01-01

    The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV. PMID:26184451

  1. Two Years Onboard the MER Opportunity Rover

    NASA Technical Reports Server (NTRS)

    Estlin, Tara; Anderson, Robert C.; Bornstein, Benjamin; Burl, Michael; Castano, Rebecca; Gaines, Daniel; Judd, Michele; Thompson, David R.

    2012-01-01

    The Autonomous Exploration for Gathering Increased Science (AEGIS) system provides automated data collection for planetary rovers. AEGIS is currently being used onboard the Mars Exploration Rover (MER) mission's Opportunity to provide autonomous targeting of the MER Panoramic camera. Prior to AEGIS, targeted data was collected in a manual fashion where targets were manually identified in images transmitted to Earth and the rover had to remain in the same location for one to several communication cycles. AEGIS enables targeted data to be rapidly acquired with no delays for ground communication. Targets are selected by AEGIS through the use of onboard data analysis techniques that are guided by scientist-specified objectives. This paper provides an overview of the how AEGIS has been used on the Opportunity rover, focusing on usage that occurred during a 21 kilometer historic trek to the Mars Endeavour crater.

  2. Barrier properties of k-mer packings

    NASA Astrophysics Data System (ADS)

    Lebovka, N.; Khrapatiy, S.; Vygornitskyi; Pivovarova, N.

    2014-08-01

    This work discusses numerical studies of the barrier properties of k-mer packings by the Monte Carlo method. The studied variants of regular and non-regular arrangements on a square lattice included models of random sequential adsorption (RSA) and random deposition (RD). The discrete problem of diffusion through the bonds of a square lattice was considered. The k-mers were perfectly oriented perpendicular to the diffusion direction and blocked certain fraction of bonds fb against diffusion. The barrier efficiency was estimated by calculation of the ratio D/Do where D is diffusion coefficient in direction perpendicular to the orientation of k-mers and Do is the same value for diffusion on the square lattice without blocked bonds, i.e., at fb=0. The value of k varied from 1 to 512 and different lattice sizes up to L=8192 lattice units were used. For dense packings (p=1), the obtained D/Do versus fb dependences deviated from the theoretical prediction of effective medium (EM) theory and deviation was the most obvious for the regular non-staggered arrangement. For loose RSA and RD packings, the percolation like-behavior of D/Do with threshold at fb=p∞ was observed and the data evidenced that their barrier properties at large values of k may be more effective than those of some dense packings. Such anomalous behavior can reflect the details of k-mer spatial organization (aggregation) and structure of pores in RD and RSA packings. The contradictions between simulation data and predictions of EM theory were also discussed.

  3. Automated Targeting for the MER Rovers

    NASA Technical Reports Server (NTRS)

    Estlin, Tara; Castano, Rebecca; Anderson, Robert C.; Bornstein, Benjamin; Gaines, Daniel; de Granville, Charles; Thompson, David; Burl, Michael; Chien, Steve; Judd, Michele

    2009-01-01

    The Autonomous Exploration for Gathering Increased Science System (AEGIS) will soon provide automated targeting for remote sensing instruments on the Mars Exploration Rover (MER) mission, which currently which currently has two rovers exploring the surface of Mars. Currently, targets for rover remote-sensing instruments, especially narrow field-of-view instruments (such as the MER Mini- TES spectrometer or the 2011 Mars Science Laboratory (MSL) Mission ChemCam Spectrometer), must be selected manually based on imagery already on the ground with the operations team. AEGIS enables the rover flight software to analyze imagery onboard in order to autonomously select and sequence targeted remote-sensing observations in an opportunistic fashion. In this paper, we first provide some background information on the larger autonomous science framework in which AEGIS was developed. We then describe how AEGIS was specifically developed and tested on the JPL FIDO rover. Finally we discuss how AEGIS will be uploaded and used on the Mars Exploration Rover (MER) mission in early 2009.

  4. Managing PV Power on Mars - MER Rovers

    NASA Technical Reports Server (NTRS)

    Stella, Paul M.; Chin, Keith; Wood, Eric; Herman, Jennifer; Ewell, Richard

    2009-01-01

    The MER Rovers have recently completed over 5 years of operation! This is a remarkable demonstration of the capabilities of PV power on the Martian surface. The extended mission required the development of an efficient process to predict the power available to the rovers on a day-to-day basis. The performance of the MER solar arrays is quite unlike that of any other Space array and perhaps more akin to Terrestrial PV operation, although even severe by that comparison. The impact of unpredictable factors, such as atmospheric conditions and dust accumulation (and removal) on the panels limits the accurate prediction of array power to short time spans. Based on the above, it is clear that long term power predictions are not sufficiently accurate to allow for detailed long term planning. Instead, the power assessment is essentially a daily activity, effectively resetting the boundary points for the overall predictive power model. A typical analysis begins with the importing of the telemetry from each rover's previous day's power subsystem activities. This includes the array power generated, battery state-of-charge, rover power loads, and rover orientation, all as functions of time. The predicted performance for that day is compared to the actual performance to identify the extent of any differences. The model is then corrected for these changes. Details of JPL's MER power analysis procedure are presented, including the description of steps needed to provide the final prediction for the mission planners. A dust cleaning event of the solar array is also highlighted to illustrate the impact of Martian weather on solar array performance

  5. MERS coronavirus: data gaps for laboratory preparedness.

    PubMed

    de Sousa, Rita; Reusken, Chantal; Koopmans, Marion

    2014-01-01

    Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, many questions remain on modes of transmission and sources of virus. In outbreak situations, especially with emerging organisms causing severe human disease, it is important to understand the full spectrum of disease, and shedding kinetics in relation to infectivity and the ability to transmit the microorganism. Laboratory response capacity during the early stages of an outbreak focuses on development of virological and immunological methods for patient diagnosis, for contact tracing, and for epidemiological studies into sources, modes of transmission, identification of risk groups, and animal reservoirs. However, optimal use of this core public health laboratory capacity requires a fundamental understanding of kinetics of viral shedding and antibody response, of assay validation and of interpretation of test outcomes. We reviewed available data from MERS-CoV case reports, and compared this with data on kinetics of shedding and immune response from published literature on other human coronaviruses (hCoVs). We identify and discuss important data gaps, and biases that limit the laboratory preparedness to this novel disease. Public health management will benefit from standardised reporting of methods used, details of test outcomes by sample type, sampling date, in relation to symptoms and risk factors, along with the currently reported demographic, clinical and epidemiological findings. PMID:24286807

  6. Science Activity Planner for the MER Mission

    NASA Technical Reports Server (NTRS)

    Norris, Jeffrey S.; Crockett, Thomas M.; Fox, Jason M.; Joswig, Joseph C.; Powell, Mark W.; Shams, Khawaja S.; Torres, Recaredo J.; Wallick, Michael N.; Mittman, David S.

    2008-01-01

    The Maestro Science Activity Planner is a computer program that assists human users in planning operations of the Mars Explorer Rover (MER) mission and visualizing scientific data returned from the MER rovers. Relative to its predecessors, this program is more powerful and easier to use. This program is built on the Java Eclipse open-source platform around a Web-browser-based user-interface paradigm to provide an intuitive user interface to Mars rovers and landers. This program affords a combination of advanced display and simulation capabilities. For example, a map view of terrain can be generated from images acquired by the High Resolution Imaging Science Explorer instrument aboard the Mars Reconnaissance Orbiter spacecraft and overlaid with images from a navigation camera (more precisely, a stereoscopic pair of cameras) aboard a rover, and an interactive, annotated rover traverse path can be incorporated into the overlay. It is also possible to construct an overhead perspective mosaic image of terrain from navigation-camera images. This program can be adapted to similar use on other outer-space missions and is potentially adaptable to numerous terrestrial applications involving analysis of data, operations of robots, and planning of such operations for acquisition of scientific data.

  7. NT-38MerTK AS A TARGET IN GLIOBLASTOMA

    PubMed Central

    Wu, Jing; Huey, Lauren; Bash, Ryan E.; Cohen, Stephanie M.; Ewend, Matthew G.; Wang, Xiaodong; Graham, Douglas K.; Frye, Stephen V.; Earp, H. Shelton; Miller, C. Ryan

    2014-01-01

    Glioma-associated macrophages and microglia (GIM) are infiltrating immune cells that modulate the glioblastoma (GBM) micro-environment. Pharmacological targeting of GIM represents a promising therapeutic strategy. MerTK receptor tyrosine kinase triggers macrophage ingestion of apoptotic material and polarizes macrophages to an M2-like, immunosuppressive phenotype that promotes tumor growth. In addition, aberrant MerTK expression in GBM tumor cells can provide pro-survival, pro-invasion and chemo-resistance signals. We examined MerTK expression by double immunofluorescence (IF) in 40 human GBM. Both GFAP+ tumor cells and CD68+ GIM expressed MerTK. Quantification in 12 matched pairs of newly-diagnosed and recurrent GBM showed a 5.5-fold increase in MerTK/CD68+ macrophages (p = 0.002), but no consistent changes in MerTK/GFAP+ tumor cells upon recurrence. Next, we examined the efficacy of a novel UNC-developed small molecule MerTK inhibitor (MerTKI) in a genetically engineered orthotopic allograft model of GBM (TRP). GBM were established for 7 days upon stereotactic injection of luciferase-expressing TRP cells into syngeneic, immune-competent mice. Mice (N = 10-12/group) were then randomized to receive no treatment, daily MerTKI (65mg/kg p.o.), or MerTKI plus fractionated radiation (XRT, 5 Gy q.o.d x3). Median survival was 24, 22, and 41.5 days, respectively (p = 0.003), while historical survival of TRP allograft mice treated with XRT alone was 30 days. Bioluminescence imaging (BLI) showed a significant growth delay in MerTKI + XRT-treated mice (doubling time 14 versus 4-4.5 days, p < 0.0001). Two mice remain alive after 50 days of combination treatment and tumor growth remains stable with 90-99% reduction in pre-treatment BLI. Post-mortem histology and IF are pending. These results suggest that both human GBM tumor cells and GIM express MerTK and that MerTK+ GIM may increase upon disease recurrence. MerTK inhibition in an immune-competent pre-clinical model may

  8. KAnalyze: a fast versatile pipelined K-mer toolkit

    PubMed Central

    Audano, Peter; Vannberg, Fredrik

    2014-01-01

    Motivation: Converting nucleotide sequences into short overlapping fragments of uniform length, k-mers, is a common step in many bioinformatics applications. While existing software packages count k-mers, few are optimized for speed, offer an application programming interface (API), a graphical interface or contain features that make it extensible and maintainable. We designed KAnalyze to compete with the fastest k-mer counters, to produce reliable output and to support future development efforts through well-architected, documented and testable code. Currently, KAnalyze can output k-mer counts in a sorted tab-delimited file or stream k-mers as they are read. KAnalyze can process large datasets with 2 GB of memory. This project is implemented in Java 7, and the command line interface (CLI) is designed to integrate into pipelines written in any language. Results: As a k-mer counter, KAnalyze outperforms Jellyfish, DSK and a pipeline built on Perl and Linux utilities. Through extensive unit and system testing, we have verified that KAnalyze produces the correct k-mer counts over multiple datasets and k-mer sizes. Availability and implementation: KAnalyze is available on SourceForge: https://sourceforge.net/projects/kanalyze/ Contact: fredrik.vannberg@biology.gatech.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24642064

  9. Genomic DNA k-mer Spectra: Models and Modalities

    NASA Astrophysics Data System (ADS)

    Chor, Benny; Horn, David; Goldman, Nick; Levy, Yaron; Massingham, Tim

    Background: The empirical frequencies of DNA k-mers in whole genome sequences provide an interesting perspective on genomic complexity, and the availability of large segments of genomic sequence from many organisms means that analysis of k-mers with non-trivial lengths is now possible.

  10. Engineering MerR for Sequestration and MerA for Reduction of Toxic Metals and Radionuclides

    SciTech Connect

    Anne O. Summers

    2008-12-15

    The objectives of this project were (1) to alter a metalloregulatory protein (MerR) so that it would bind other toxic metals or radionuclides with similar affinity so that the engineered protein itself and/or bacteria expressing it could be deployed in the environment to specifically sequester such metals and (2) to alter the mercuric reductase, MerA, to reduce radionuclides and render them less mobile. Both projects had a basic science component. In the first case, such information about MerR illuminates how proteins discriminate very similar metals/elements. In the second case, information about MerA reveals the criteria for transmission of reducing equivalents from NADPH to redox-active metals. The work involved genetic engineering of all or parts of both proteins and examination of their resultant properties both in vivo and in vitro, the latter with biochemical and biophysical tools including equilibrium and non-equilibrium dialysis, XAFS, NMR, x-ray crystallography, and titration calorimetry. We defined the basis for metal specificity in MerR, devised a bacterial strain that sequesters Hg while growing, characterized gold reduction by MerA and the role of the metallochaperone domain of MerA, and determined the 3-D structure of MerB, the organomercurial lyase.

  11. The Ames MER microscopic imager toolkit

    USGS Publications Warehouse

    Sargent, R.; Deans, Matthew; Kunz, C.; Sims, M.; Herkenhoff, K.

    2005-01-01

    12The Mars Exploration Rovers, Spirit and Opportunity, have spent several successful months on Mars, returning gigabytes of images and spectral data to scientists on Earth. One of the instruments on the MER rovers, the Athena Microscopic Imager (MI), is a fixed focus, megapixel camera providing a ??3mm depth of field and a 31??31mm field of view at a working distance of 63 mm from the lens to the object being imaged. In order to maximize the science return from this instrument, we developed the Ames MI Toolkit and supported its use during the primary mission. The MI Toolkit is a set of programs that operate on collections of MI images, with the goal of making the data more understandable to the scientists on the ground. Because of the limited depth of field of the camera, and the often highly variable topography of the terrain being imaged, MI images of a given rock are often taken as a stack, with the Instrument Deployment Device (IDD) moving along a computed normal vector, pausing every few millimeters for the MI to acquire an image. The MI Toolkit provides image registration and focal section merging, which combine these images to form a single, maximally in-focus image, while compensating for changes in lighting as well as parallax due to the motion of the camera. The MI Toolkit also provides a 3-D reconstruction of the surface being imaged using stereo and can embed 2-D MI images as texture maps into 3-D meshes produced by other imagers on board the rover to provide context. The 2-D images and 3-D meshes output from the Toolkit are easily viewed by scientists using other mission tools, such as Viz or the MI Browser.This paper describes the MI Toolkit in detail, as well as our experience using it with scientists at JPL during the primary MER mission. ?? 2005 IEEE.

  12. The Ames MER Microscopic Imager Toolkit

    NASA Technical Reports Server (NTRS)

    Sargent, Randy; Deans, Matthew; Kunz, Clayton; Sims, Michael; Herkenhoff, Ken

    2005-01-01

    The Mars Exploration Rovers, Spirit and Opportunity, have spent several successful months on Mars, returning gigabytes of images and spectral data to scientists on Earth. One of the instruments on the MER rovers, the Athena Microscopic Imager (MI), is a fixed focus, megapixel camera providing a plus or minus mm depth of field and a 3lx31mm field of view at a working distance of 63 mm from the lens to the object being imaged. In order to maximize the science return from this instrument, we developed the Ames MI Toolkit and supported its use during the primary mission. The MI Toolkit is a set of programs that operate on collections of MI images, with the goal of making the data more understandable to the scientists on the ground. Because of the limited depth of field of the camera, and the often highly variable topography of the terrain being imaged, MI images of a given rock are often taken as a stack, with the Instrument Deployment Device (IDD) moving along a computed normal vector, pausing every few millimeters for the MI to acquire an image. The MI Toolkit provides image registration and focal section merging, which combine these images to form a single, maximally in-focus image, while compensating for changes in lighting as well as parallax due to the motion of the camera. The MI Toolkit also provides a 3-D reconstruction of the surface being imaged using stereo and can embed 2-D MI images as texture maps into 3-D meshes produced by other imagers on board the rover to provide context. The 2-D images and 3-D meshes output from the Toolkit are easily viewed by scientists using other mission tools, such as Viz or the MI Browser. This paper describes the MI Toolkit in detail, as well as our experience using it with scientists at JPL during the primary MER mission.

  13. mer [Römer, Roemer], Ole [Olaf] Christensen (1644-1710)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Born in Aarhus, Denmark, studied at the University of Copenhagen under Thomas and Erasmus Bartholin, who gave him TYCHO BRAHE's manuscripts to edit and his own daughter to wed. Rømer accompanied Bartholin and JEAN PICARD to Hven to measure the position of Tycho's observatory, the better to reduce Tycho's observations. He went on to the Paris Observatory where he made and used instruments for the ...

  14. Recombination spot identification Based on gapped k-mers

    PubMed Central

    Wang, Rong; Xu, Yong; Liu, Bin

    2016-01-01

    Recombination is crucial for biological evolution, which provides many new combinations of genetic diversity. Accurate identification of recombination spots is useful for DNA function study. To improve the prediction accuracy, researchers have proposed several computational methods for recombination spot identification. The k-mer feature is one of the most useful features for modeling the properties and function of DNA sequences. However, it suffers from the inherent limitation. If the value of word length k is large, the occurrences of k-mers are closed to a binary variable, with a few k-mers present once and most k-mers are absent. This usually causes the sparse problem and reduces the classification accuracy. To solve this problem, we add gaps into k-mer and introduce a new feature called gapped k-mer (GKM) for identification of recombination spots. By using this feature, we present a new predictor called SVM-GKM, which combines the gapped k-mers and Support Vector Machine (SVM) for recombination spot identification. Experimental results on a widely used benchmark dataset show that SVM-GKM outperforms other highly related predictors. Therefore, SVM-GKM would be a powerful predictor for computational genomics. PMID:27030570

  15. Recombination spot identification Based on gapped k-mers.

    PubMed

    Wang, Rong; Xu, Yong; Liu, Bin

    2016-01-01

    Recombination is crucial for biological evolution, which provides many new combinations of genetic diversity. Accurate identification of recombination spots is useful for DNA function study. To improve the prediction accuracy, researchers have proposed several computational methods for recombination spot identification. The k-mer feature is one of the most useful features for modeling the properties and function of DNA sequences. However, it suffers from the inherent limitation. If the value of word length k is large, the occurrences of k-mers are closed to a binary variable, with a few k-mers present once and most k-mers are absent. This usually causes the sparse problem and reduces the classification accuracy. To solve this problem, we add gaps into k-mer and introduce a new feature called gapped k-mer (GKM) for identification of recombination spots. By using this feature, we present a new predictor called SVM-GKM, which combines the gapped k-mers and Support Vector Machine (SVM) for recombination spot identification. Experimental results on a widely used benchmark dataset show that SVM-GKM outperforms other highly related predictors. Therefore, SVM-GKM would be a powerful predictor for computational genomics. PMID:27030570

  16. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Cancer.gov

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  17. MGS and Odyssey - relay satellites for the MER mission

    NASA Technical Reports Server (NTRS)

    Esposito, Pasquale B.; Bhat, R.; Demeak, S.; Ardalan, S.; Breeden, J.; Helfrich, C.; Jefferson, D.; Stauch, J.

    2004-01-01

    Both Mars Global Surveyor (MGS) and Odyssey are currently in low altitude, nearly circular and highly inclined orbits about Mars. Thus, they are available adn compartible to serve as relay satellites for the Mars Exploration Rovers (MER) mission. Consequently, the MER project developed requirements for MGS to be overhead for MER-A (Spirit) at Gusev crater, at maximum elevation, mudway between lander separation and initial touchdown; in time, this was specified as 01/04/04. 04:24:55 UTC/SCET with a 30 sec tolerance.

  18. Translating MAPGEN to ASPEN for MER

    NASA Technical Reports Server (NTRS)

    Rabideau, Gregg R.; Knight, Russell L.; Lenda, Matthew; Maldague, Pierre F.

    2013-01-01

    This software translates MAPGEN (Europa and APGEN) domains to ASPEN, and the resulting domain can be used to perform planning for the Mars Exploration Rover (MER). In other words, this is a conversion of two distinct planning languages (both declarative and procedural) to a third (declarative) planning language in order to solve the problem of faithful translation from mixed-domain representations into the ASPEN Modeling Language. The MAPGEN planning system is an example of a hybrid procedural/declarative system where the advantages of each are leveraged to produce an effective planner/scheduler for MER tactical planning. The adaptation of the planning system (ASPEN) was investigated, and, with some translation, much of the procedural knowledge encoding is amenable to declarative knowledge encoding. The approach was to compose translators from the core languages used for adapting MAGPEN, which consists of Europa and APGEN. Europa is a constraint- based planner/scheduler where domains are encoded using a declarative model. APGEN is also constraint-based, in that it tracks constraints on resources and states and other variables. Domains are encoded in both constraints and code snippets that execute according to a forward sweep through the plan. Europa and APGEN communicate to each other using proxy activities in APGEN that represent constraints and/or tokens in Europa. The composition of a translator from Europa to ASPEN was fairly straightforward, as ASPEN is also a declarative planning system, and the specific uses of Europa for the MER domain matched ASPEN s native encoding fairly closely. On the other hand, translating from APGEN to ASPEN was considerably more involved. On the surface, the types of activities and resources one encodes in APGEN appear to match oneto- one to the activities, state variables, and resources in ASPEN. But, when looking into the definitions of how resources are profiled and activities are expanded, one sees code snippets that access

  19. PERFORMANCE CHARACTERISTICS OF 65-MER OLIGONUCLEOTIDE MICROARRAYS

    PubMed Central

    Lee, Myoyong; Xiang, Charlie C.; Trent, Jeffrey M.; Bittner, Michael L.

    2009-01-01

    Microarray fabrication using pre-synthesized long oligonucleotide is becoming increasingly important, but a study of large-scale array productions is not published yet. We addressed the issue of fabricating oligonucleotide microarrays by spotting commercial, pre-synthesized 65-mers with 5′ amines representing 7500 murine genes. Amine-modified oligonucleotides were immobilized on glass slides having aldehyde groups via transient Schiff base formation followed by reduction to produce a covalent conjugate. When RNA derived from the same source was used for Cy3 and Cy5 labeling and hybridized to the same array, signal intensities spanning three orders of magnitude were observed, and the coefficient of variation between the two channels for all spots was 8–10%. To ascertain the reproducibility of ratio determination of these arrays, two triplicate hybridizations (with fluorochrome reversal) comparing RNAs from a fibroblast (NIH3T3) and a breast cancer (JC) cell line were carried out. The 95% confidence interval for all spots in the six hybridizations was 0.60 – 1.66. This level of reproducibility allows use of the full range of pattern finding and discriminant analysis typically applied to cDNA microarrays. Further comparative testing was carried out with oligonucleotide microarrays, cDNA microarrays and RT-PCR assays to examine the comparability of results across these different methodologies. PMID:17617369

  20. SARS and MERS: recent insights into emerging coronaviruses.

    PubMed

    de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl; Munster, Vincent J

    2016-08-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. PMID:27344959

  1. WATER ON MARS: EVIDENCE FROM MER MISSION RESULTS

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    2006-01-01

    The Mars Exploration Rover (MER) mission landed two rovers on Mars, equipped with a highly-capable suite of science instruments. The Spirit rover landed on the inside Gusev Crater on January 5, 2004, and the Opportunity rover three weeks later on Meridiani Planum. This paper summarizes some of the findings from the MER rovers related to the NASA science strategy of investigating past and present water on Mars.

  2. Self-assembly of 33-mer gliadin peptide oligomers.

    PubMed

    Herrera, M G; Benedini, L A; Lonez, C; Schilardi, P L; Hellweg, T; Ruysschaert, J-M; Dodero, V I

    2015-11-28

    The 33-mer gliadin peptide, LQLQPF(PQPQLPY)3PQPQPF, is a highly immunogenic peptide involved in celiac disease and probably in other immunopathologies associated with gliadin. Herein, dynamic light scattering measurements showed that 33-mer, in the micromolar concentration range, forms polydisperse nano- and micrometer range particles in aqueous media. This behaviour is reminiscent of classical association of colloids and we hypothesized that the 33-mer peptide self-assembles into micelles that could be the precursors of 33-mer oligomers in water. Deposition of 33-mer peptide aqueous solution on bare mica generated nano- and microstructures with different morphologies as revealed by atomic force microscopy. At 6 μM, the 33-mer is organised in isolated and clusters of spherical nanostructures. In the 60 to 250 μM concentration range, the spherical oligomers associated mainly in linear and annular arrangements and structures adopting a "sheet" type morphology appeared. At higher concentrations (610 μM), mainly filaments and plaques immersed in a background of nanospherical structures were detected. The occurrence of different morphologies of oligomers and finally the filaments suggests that the unique specific geometry of the 33-mer oligomers has a crucial role in the subsequent condensation and organization of their fractal structures into the final filaments. The self-assembly process on mica is described qualitatively and quantitatively by a fractal diffusion limited aggregation (DLA) behaviour with the fractal dimension in the range of 1.62 ± 0.02 to 1.73 ± 0.03. Secondary structure evaluation of the oligomers by Attenuated Total Reflection FTIR spectroscopy (ATR-FTIR) revealed the existence of a conformational equilibrium of self-assembled structures, from an extended conformation to a more folded parallel beta elongated structures. Altogether, these findings provide structural and morphological information about supramolecular organization of the 33-mer

  3. Role of MerH in mercury resistance in the archaeon Sulfolobus solfataricus

    PubMed Central

    Schelert, James; Rudrappa, Deepak; Johnson, Tyler

    2013-01-01

    Crenarchaeota include extremely thermoacidophilic organisms that thrive in geothermal environments dominated by sulfidic ores and heavy metals such as mercury. Mercuric ion, Hg(II), inactivates transcription in the crenarchaeote Sulfolobus solfataricus and simultaneously derepresses transcription of a resistance operon, merHAI, through interaction with the MerR transcription factor. While mercuric reductase (MerA) is required for metal resistance, the role of MerH, an adjacent small and predicted product of an ORF, has not been explored. Inactivation of MerH either by nonsense mutation or by in-frame deletion diminished Hg(II) resistance of mutant cells. Promoter mapping studies indicated that Hg(II) sensitivity of the merH nonsense mutant arose through transcriptional polarity, and its metal resistance was restored partially by single copy merH complementation. Since MerH was not required in vitro for MerA-catalysed Hg(II) reduction, MerH may play an alternative role in metal resistance. Inductively coupled plasma-mass spectrometry analysis of the MerH deletion strain following metal challenge indicated that there was prolonged retention of intracellular Hg(II). Finally, a reduced rate of mer operon induction in the merH deletion mutant suggested that the requirement for MerH could result from metal trafficking to the MerR transcription factor. PMID:23619003

  4. Evaluation of candidate vaccine approaches for MERS-CoV

    DOE PAGESBeta

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; et al

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanismsmore » were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.« less

  5. Evaluation of candidate vaccine approaches for MERS-CoV

    SciTech Connect

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; Yang, Zhi-yong; Chen, Xuejun; Becker, Michelle M.; Freeman, Megan; Vogel, Leatrice; Johnson, Joshua C.; Olinger, Gene; Todd, John P.; Bagci, Ulas; Solomon, Jeffrey; Mollura, Daniel J.; Hensley, Lisa; Jahrling, Peter; Denison, Mark R.; Rao, Srinivas S.; Subbarao, Kanta; Kwong, Peter D.; Mascola, John R.; Kong, Wing-Pui; Graham, Barney S.

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

  6. Evaluation of candidate vaccine approaches for MERS-CoV

    PubMed Central

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; Yang, Zhi-yong; Chen, Xuejun; Becker, Michelle M.; Freeman, Megan; Vogel, Leatrice; Johnson, Joshua C.; Olinger, Gene; Todd, John P.; Bagci, Ulas; Solomon, Jeffrey; Mollura, Daniel J.; Hensley, Lisa; Jahrling, Peter; Denison, Mark R.; Rao, Srinivas S.; Subbarao, Kanta; Kwong, Peter D.; Mascola, John R.; Kong, Wing-Pui; Graham, Barney S.

    2015-01-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development. PMID:26218507

  7. Systolic dysfunction in cardiac-specific ligand-inducible MerCreMer transgenic mice

    PubMed Central

    Hall, Michael E.; Smith, Grant; Hall, John E.

    2011-01-01

    The Cre-loxP system is a useful tool to study the physiological effects of gene knockout in the heart. One limitation with using this system in the heart is the toxic effect of chronic expression of the Cre recombinase. To circumvent this limitation, a widely used inducible cardiac-specific model, Myh6-MerCreMer (Cre), using tamoxifen (TAM) to activate Cre has been developed. The current study examined cardiac function in Cre-positive C57B/J6 mice exposed to one, three, or five daily doses of a 40 mg/kg TAM to induce Cre activity specifically in the heart. Echocardiography demonstrated no statistically significant differences in systolic function (SF) at baseline as assessed by fractional shortening. In mice exposed to five injections, a significant fall in all determinants of SF was observed 6 days after TAM was initiated. However, SF returned to baseline levels 10 days after TAM initiation although the hearts exhibited significant hypertrophy. Heart weight-to-tibia length ratios were 73 ± 3, 78.5 ± 6, and 87.6 ± 9 mg/cm for one, three, and five TAM injections, respectively. TAM had no effect on cardiac function or hypertrophy in Cre-negative mice. Cre-positive mice receiving five TAM injections had significant reductions in cardiac mitochondrial ATP and significant reductions in the expression of proteins important for the regulation of cardiac oxidative phosphorylation including peroxisome proliferator-activated receptor-γ coactivator-1α and pyruvate dehydrogenase kinase-4. Thus inducible cardiac-specific activation of Cre recombinase caused a transient decline in SF that was dependent on the number of TAM doses and associated with significant hypertrophy and alterations in mitochondrial ATP and important proteins involved in the regulation of cardiac oxidative phosphorylation. PMID:21536850

  8. Model for the distributions of k -mers in DNA sequences

    NASA Astrophysics Data System (ADS)

    Chen, Yaw-Hwang; Nyeo, Su-Long; Yeh, Chiung-Yuh

    2005-07-01

    The evolutionary features based on the distributions of k -mers in the DNA sequences of various organisms are studied. The organisms are classified into three groups based on their evolutionary periods: (a) E. coli and T. pallidum (b) yeast, zebrafish, A. thaliana, and fruit fly, (c) mouse, chicken, and human. The distributions of 6-mers of these three groups are shown to be, respectively, (a) unimodal, (b) unimodal with peaks generally shifted to smaller frequencies of occurrence, (c) bimodal. To describe the bimodal feature of the k -mer distributions of group (c), a model based on the cytosine-guanine “ CG ” content of the DNA sequences is introduced and shown to provide reasonably good agreements.

  9. A stable mercury-containing complex of the organomercurial lyase MerB: catalysis, product release, and direct transfer to MerA.

    PubMed

    Benison, Gregory C; Di Lello, Paola; Shokes, Jacob E; Cosper, Nathaniel J; Scott, Robert A; Legault, Pascale; Omichinski, James G

    2004-07-01

    Bacteria isolated from organic mercury-contaminated sites have developed a system of two enzymes that allows them to efficiently convert both ionic and organic mercury compounds to the less toxic elemental mercury. Both enzymes are encoded on the mer operon and require sulfhydryl-bound substrates. The first enzyme is an organomercurial lyase (MerB), and the second enzyme is a mercuric ion reductase (MerA). MerB catalyzes the protonolysis of the carbon-mercury bond, resulting in the formation of a reduced carbon compound and inorganic ionic mercury. Of several mercury-containing MerB complexes that we attempted to prepare, the most stable was a complex consisting of the organomercurial lyase (MerB), a mercuric ion, and a molecule of the MerB inhibitor dithiothreitol (DTT). Nuclear magnetic resonance (NMR) spectroscopy and extended X-ray absorption fine structure spectroscopy of the MerB/Hg/DTT complex have shown that the ligands to the mercuric ion in the complex consist of both sulfurs from the DTT molecule and one cysteine ligand, C96, from the protein. The stability of the MerB/Hg/DTT complex, even in the presence of a large excess of competing cysteine, has been demonstrated by NMR and dialysis. We used an enzyme buffering test to determine that the MerB/Hg/DTT complex acts as a substrate for the mercuric reductase MerA. The observed MerA activity is higher than the expected activity assuming free diffusion of the mercuric ion from MerB to MerA. This suggests that the mercuric ion can be transferred between the two enzymes by a direct transfer mechanism. PMID:15222746

  10. Cassini, Rømer, and the velocity of light

    NASA Astrophysics Data System (ADS)

    Bobis, Laurence; Lequeux, James

    2008-07-01

    The discovery of the finite nature of the velocity of light is usually attributed to Rømer. However, a text at the Paris Observatory confirms the minority opinion according to which Cassini was first to propose the ‘successive motion’ of light, while giving a rather correct order of magnitude for the duration of its propagation from the Sun to the Earth. We examine this question, and discuss why, in spite of the criticisms of Halley, Cassini abandoned this hypothesis while leaving Rømer free to publish it.

  11. The Ballerina Experiment on the Rømer Mission

    NASA Astrophysics Data System (ADS)

    Brandt, Soren

    The Rømer mission has recently been approved as the next mission within the Danish Small Satellite Program. The scientific payload will consist of two separate experiments, the MONS and the Ballerina payloads. The primary objective of Ballerina is to provide accurate, real-time positions relayed to ground for ~ 70 Gamma Ray Bursts (GRBs) per year, and to study the temporal and spectral evolution of the early GRB X-ray afterglow. As an additional goal, Ballerina will detect and study bright X-ray transients, in particular X-ray novae and micro-quasar systems. R{\\o}mer is currently scheduled for launch in late 2003.

  12. Vaccines for the prevention against the threat of MERS-CoV.

    PubMed

    Du, Lanying; Tai, Wanbo; Zhou, Yusen; Jiang, Shibo

    2016-09-01

    First identified in 2012, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is listed as a new Category C Priority Pathogen. While the high mortality of MERS-CoV infection is further intensified by potential human-to-human transmissibility, no MERS vaccines are available for human use. This review explains immune responses resulting from MERS-CoV infection, describes MERS vaccine criteria, and presents available small animal models to evaluate the efficacy of MERS vaccines. Current advances in vaccine development are summarized, focusing on specific applications and limitations of each vaccine category. Taken together, this review provides valuable guidelines toward the development of an effective and safe MERS vaccine. This article is written for a Special Focus Issue of Expert Review of Vaccines on 'Vaccines for Biodefence'. PMID:26985862

  13. Planning Mars Memory: Learning from the MER Mission

    NASA Technical Reports Server (NTRS)

    Charlotte, Linde

    2004-01-01

    This viewgraph presentation discusses ways in which the lessons learned from a mission can be systematically remembered, retained, and applied by individuals and by an organization as a whole. The presentation cites lessons learned from the Mars Exploration Rover (MER) Mission as examples.

  14. Characterization of MER Landing Sites Using MOC and MOLA

    NASA Technical Reports Server (NTRS)

    Anderson, F. S.; Parker, T. J.

    2002-01-01

    The MOC images for MER are compared with MOLA data to characterize and locate each image. MOLA profiles show that Hematite remains benign, Melas and Isidis are rougher, and Athabasca and Gusev have regions of significant small scale topography. Additional information is contained in the original extended abstract.

  15. ROLE OF NA+ IN TRANSPORT OF HG2+ AND INDUCTION OF THE TN21 "MER" OPERON

    EPA Science Inventory

    The effects of sodium ions on the uptake of Hg 2 + and induction of the TN21 mer operon were studied using E. coli HMS174 harboring the reporter plasmids pRB28 and pOS14. lasmid pRB28 carries merRT' and pOS14 carries merRTPC of the mer operon, both cloned upstream of a promoterle...

  16. MERS-CoV Antibodies in Humans, Africa, 2013-2014.

    PubMed

    Liljander, Anne; Meyer, Benjamin; Jores, Joerg; Müller, Marcel A; Lattwein, Erik; Njeru, Ian; Bett, Bernard; Drosten, Christian; Corman, Victor Max

    2016-06-01

    Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014. PMID:27071076

  17. Antenna Designs for the Mars Exploration Rovers (MER) Spacecraft, Lander, and Rover

    NASA Technical Reports Server (NTRS)

    Vacchione, Joseph; Thelen, Michael; Brown, Paula; Huang, John; Kelly, Ken; Krishnan, Satish

    2001-01-01

    This presentation focuses on the design of antennas for the Mars Exploration Rovers (MER). Specific topics covered include: MER spacecraft architecture, the evolution of an antenna system, MER cruise stage antennas, antenna stacks, the heat-shield/back shell antenna, and lander and rover antennas. Additionally, the mission's science objectives are reviewed.

  18. MERS-CoV Antibodies in Humans, Africa, 2013–2014

    PubMed Central

    Liljander, Anne; Meyer, Benjamin; Jores, Joerg; Müller, Marcel A.; Lattwein, Erik; Njeru, Ian; Bett, Bernard; Corman, Victor Max

    2016-01-01

    Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014. PMID:27071076

  19. Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections

    PubMed Central

    Ying, Tianlei; Li, Haoyang; Lu, Lu; Dimitrov, Dimiter S; Jiang, Shibo

    2014-01-01

    The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections. PMID:25456101

  20. Unraveling the drivers of MERS-CoV transmission.

    PubMed

    Cauchemez, Simon; Nouvellet, Pierre; Cori, Anne; Jombart, Thibaut; Garske, Tini; Clapham, Hannah; Moore, Sean; Mills, Harriet Linden; Salje, Henrik; Collins, Caitlin; Rodriquez-Barraquer, Isabel; Riley, Steven; Truelove, Shaun; Algarni, Homoud; Alhakeem, Rafat; AlHarbi, Khalid; Turkistani, Abdulhafiz; Aguas, Ricardo J; Cummings, Derek A T; Van Kerkhove, Maria D; Donnelly, Christl A; Lessler, Justin; Fraser, Christophe; Al-Barrak, Ali; Ferguson, Neil M

    2016-08-01

    With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain. PMID:27457935

  1. Unraveling the drivers of MERS-CoV transmission

    PubMed Central

    Cauchemez, Simon; Nouvellet, Pierre; Cori, Anne; Jombart, Thibaut; Clapham, Hannah; Moore, Sean; Mills, Harriet Linden; Salje, Henrik; Collins, Caitlin; Rodriquez-Barraquer, Isabel; Riley, Steven; Truelove, Shaun; Algarni, Homoud; Alhakeem, Rafat; AlHarbi, Khalid; Turkistani, Abdulhafiz; Aguas, Ricardo J.; Cummings, Derek A. T.; Van Kerkhove, Maria D.; Donnelly, Christl A.; Lessler, Justin; Fraser, Christophe; Al-Barrak, Ali; Ferguson, Neil M.

    2016-01-01

    With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain. PMID:27457935

  2. Demonstration of Mer-Cure Technology for Enhanced Mercury Control

    SciTech Connect

    John Marion; Dave O'Neill; Kevin Taugher; Shin Kang; Mark Johnson; Gerald Pargac; Jane Luedecke; Randy Gardiner; Mike Silvertooth; Jim Hicks; Carl Edberg; Ray Cournoyer; Stanley Bohdanowicz; Ken Peterson; Kurt Johnson; Steve Benson; Richard Schulz; Don McCollor; Mike Wuitshick

    2008-06-01

    Alstom Power Inc. has completed a DOE/NETL-sponsored program (under DOE Cooperative Agreement No. De-FC26-07NT42776) to demonstrate Mer-Cure{trademark}, one of Alstom's mercury control technologies for coal-fired boilers. The Mer-Cure{trademark}system utilizes a small amount of Mer-Clean{trademark} sorbent that is injected into the flue gas stream for oxidation and adsorption of gaseous mercury. Mer-Clean{trademark} sorbents are carbon-based and prepared with chemical additives that promote oxidation and capture of mercury. The Mer-Cure{trademark} system is unique in that the sorbent is injected into an environment where the mercury capture kinetics is accelerated. The full-scale demonstration program originally included test campaigns at two host sites: LCRA's 480-MW{sub e} Fayette Unit No.3 and Reliant Energy's 190-MW{sub e} Shawville Unit No.3. The only demonstration tests actually done were the short-term tests at LCRA due to budget constraints. This report gives a summary of the demonstration testing at Fayette Unit No.3. The goals for this Mercury Round 3 program, established by DOE/NETL under the original solicitation, were to reduce the uncontrolled mercury emissions by 90% at a cost significantly less than 50% of the previous target of $60,000/lb mercury removed. The results indicated that Mer-Cure{trademark} technology could achieve mercury removal of 90% based on uncontrolled stack emissions. The estimated costs for 90% mercury control, at a sorbent cost of $0.75 to $2.00/lb respectively, were $13,400 to $18,700/lb Hg removed. In summary, the results from demonstration testing show that the goals established by DOE/NETL were met during this test program. The goal of 90% mercury reduction was achieved. Estimated mercury removal costs were 69-78% lower than the benchmark of $60,000/lb mercury removed, significantly less than 50% of the baseline removal cost.

  3. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    SciTech Connect

    Lee, Ye-Ji; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

    2012-08-15

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ►Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ►Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ►TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  4. These Are Not the K-mers You Are Looking For: Efficient Online K-mer Counting Using a Probabilistic Data Structure

    PubMed Central

    Zhang, Qingpeng; Pell, Jason; Canino-Koning, Rosangela; Howe, Adina Chuang; Brown, C. Titus

    2014-01-01

    K-mer abundance analysis is widely used for many purposes in nucleotide sequence analysis, including data preprocessing for de novo assembly, repeat detection, and sequencing coverage estimation. We present the khmer software package for fast and memory efficient online counting of k-mers in sequencing data sets. Unlike previous methods based on data structures such as hash tables, suffix arrays, and trie structures, khmer relies entirely on a simple probabilistic data structure, a Count-Min Sketch. The Count-Min Sketch permits online updating and retrieval of k-mer counts in memory which is necessary to support online k-mer analysis algorithms. On sparse data sets this data structure is considerably more memory efficient than any exact data structure. In exchange, the use of a Count-Min Sketch introduces a systematic overcount for k-mers; moreover, only the counts, and not the k-mers, are stored. Here we analyze the speed, the memory usage, and the miscount rate of khmer for generating k-mer frequency distributions and retrieving k-mer counts for individual k-mers. We also compare the performance of khmer to several other k-mer counting packages, including Tallymer, Jellyfish, BFCounter, DSK, KMC, Turtle and KAnalyze. Finally, we examine the effectiveness of profiling sequencing error, k-mer abundance trimming, and digital normalization of reads in the context of high khmer false positive rates. khmer is implemented in C++ wrapped in a Python interface, offers a tested and robust API, and is freely available under the BSD license at github.com/ged-lab/khmer. PMID:25062443

  5. Constitutive synthesis of a transport function encoded by the Thiobacillus ferrooxidans merC gene cloned in Escherichia coli

    SciTech Connect

    Kusano, Tomonobu Akita Prefectural College of Agriculture ); Ji, Guangyong; Silver, S. ); Inoue, Chihiro )

    1990-05-01

    Mercuric reductase activity determined by the Thiobacillus ferrooxidans merA gene (cloned and expressed constitutively in Escherichia coli) was measured by volatilization of {sup 203}Hg{sup 2+}. (The absence of a merR regulatory gene in the cloned Thiobacillus mer determinant provides a basis for the constitutive synthesis of this system.) In the absence of the Thiobacillus merC transport gene, the mercury volatilization activity was cryptic and was not seen with whole cells but only with sonication-disrupted cells. The Thiobacillus merC transport function was compared with transport via the merT-merP system of plasmid pDU1358. Both systems, cloned and expressed in E. coli, governed enhanced uptake of {sup 203}Hg{sup 2+} in a temperature- and concentration-dependent fashion. Uptake via MerT-MerP was greater and conferred greater hypersensitivity to Hg{sup 2+} than did uptake with MerC. Mercury uptake was inhibited by N-ethylmaleimide but not by EDTA. Ag{sup +} salts inhibited mercury uptake by the MerT-MerP system but did not inhibit uptake via MerC. Radioactive mercury accumulated by the MerT-MerP and by the MerC systems was exchangeable with nonradioactive Hg{sup 2+}.

  6. Computational Performance Assessment of k-mer Counting Algorithms.

    PubMed

    Pérez, Nelson; Gutierrez, Miguel; Vera, Nelson

    2016-04-01

    This article is about the assessment of several tools for k-mer counting, with the purpose to create a reference framework for bioinformatics researchers to identify computational requirements, parallelizing, advantages, disadvantages, and bottlenecks of each of the algorithms proposed in the tools. The k-mer counters evaluated in this article were BFCounter, DSK, Jellyfish, KAnalyze, KHMer, KMC2, MSPKmerCounter, Tallymer, and Turtle. Measured parameters were the following: RAM occupied space, processing time, parallelization, and read and write disk access. A dataset consisting of 36,504,800 reads was used corresponding to the 14th human chromosome. The assessment was performed for two k-mer lengths: 31 and 55. Obtained results were the following: pure Bloom filter-based tools and disk-partitioning techniques showed a lesser RAM use. The tools that took less execution time were the ones that used disk-partitioning techniques. The techniques that made the major parallelization were the ones that used disk partitioning, hash tables with lock-free approach, or multiple hash tables. PMID:26982880

  7. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis).

    PubMed

    Munster, Vincent J; Adney, Danielle R; van Doremalen, Neeltje; Brown, Vienna R; Miazgowicz, Kerri L; Milne-Price, Shauna; Bushmaker, Trenton; Rosenke, Rebecca; Scott, Dana; Hawkinson, Ann; de Wit, Emmie; Schountz, Tony; Bowen, Richard A

    2016-01-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV. PMID:26899616

  8. MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.

    PubMed

    Yeung, Man-Lung; Yao, Yanfeng; Jia, Lilong; Chan, Jasper F W; Chan, Kwok-Hung; Cheung, Kwok-Fan; Chen, Honglin; Poon, Vincent K M; Tsang, Alan K L; To, Kelvin K W; Yiu, Ming-Kwong; Teng, Jade L L; Chu, Hin; Zhou, Jie; Zhang, Qing; Deng, Wei; Lau, Susanna K P; Lau, Johnson Y N; Woo, Patrick C Y; Chan, Tak-Mao; Yung, Susan; Zheng, Bo-Jian; Jin, Dong-Yan; Mathieson, Peter W; Qin, Chuan; Yuen, Kwok-Yung

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. PMID:27572168

  9. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis)

    PubMed Central

    Munster, Vincent J.; Adney, Danielle R.; van Doremalen, Neeltje; Brown, Vienna R.; Miazgowicz, Kerri L.; Milne-Price, Shauna; Bushmaker, Trenton; Rosenke, Rebecca; Scott, Dana; Hawkinson, Ann; de Wit, Emmie; Schountz, Tony; Bowen, Richard A.

    2016-01-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV. PMID:26899616

  10. Segmented K-mer and its application on similarity analysis of mitochondrial genome sequences.

    PubMed

    Yu, Hong-Jie

    2013-04-15

    K-mer-based approach has been widely used in similarity analyses so as to discover similarity/dissimilarity among different biological sequences. In this study, we have improved the traditional K-mer method, and introduce a segmented K-mer approach (s-K-mer). After each primary sequence is divided into several segments, we simultaneously transform all these segments into corresponding K-mer-based vectors. In this approach, it is vital how to determine the optimal combination of distance metric with the number of K and the number of segments, i.e., (K(⁎), s(⁎), and d(⁎)). Based on the cascaded feature vectors transformed from s(⁎) segmented sequences, we analyze 34 mammalian genome sequences using the proposed s-K-mer approach. Meanwhile, we compare the results of s-K-mer with those of traditional K-mer. The contrastive analysis results demonstrate that s-K-mer approach outperforms the traditionally K-mer method on similarity analysis among different species. PMID:23353775

  11. Evaluation of MerCAP for Power Plant Mercury Control

    SciTech Connect

    Carl Richardson

    2008-09-30

    This report is submitted to the U.S. Department of Energy National Energy Technology Laboratory (DOE-NETL) as part of Cooperative Agreement DE-FC26-03NT41993, 'Evaluation of EPRI's MerCAP{trademark} Technology for Power Plant Mercury Control'. This project has investigated the mercury removal performance of EPRI's Mercury Capture by Amalgamation Process (MerCAP{trademark}) technology. Test programs were conducted to evaluate gold-based MerCAP{trademark} at Great River Energy's Stanton Station Unit 10 (Site 1), which fired both North Dakota lignite (NDL) and Power River Basin (PRB) coal during the testing period, and at Georgia Power's Plant Yates Unit 1 (Site 2) [Georgia Power is a subsidiary of The Southern Company] which fires a low sulfur Eastern bituminous coal. Additional tests were carried out at Alabama Power's Plant Miller, which fires Powder River Basin Coal, to evaluate a carbon-based MerCAP{trademark} process for removing mercury from flue gas downstream of an electrostatic precipitator [Alabama Power is a subsidiary of The Southern Company]. A full-scale gold-based sorbent array was installed in the clean-air plenum of a single baghouse compartment at GRE's Stanton Station Unit 10, thereby treating 1/10th of the unit's exhaust gas flow. The substrates that were installed were electroplated gold screens oriented parallel to the flue gas flow. The sorbent array was initially installed in late August of 2004, operating continuously until its removal in July 2006, after nearly 23 months. The initial 4 months of operation were conducted while the host unit was burning North Dakota lignite (NDL). In November 2004, the host unit switched fuel to burn Powder River Basin (PRB) subbituminous coal and continued to burn the PRB fuel for the final 19 months of this program. Tests were conducted at Site 1 to evaluate the impacts of flue gas flow rate, sorbent plate spacing, sorbent pre-cleaning and regeneration, and spray dryer operation on Mer

  12. Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia

    PubMed Central

    Lee-Sherick, A B; Eisenman, K M; Sather, S; McGranahan, A; Armistead, P M; McGary, C S; Hunsucker, S A; Schlegel, J; Martinson, H; Cannon, C; Keating, A K; Earp, H S; Liang, X; DeRyckere, D; Graham, D K

    2013-01-01

    Acute myeloid leukemia (AML) continues to be extremely difficult to treat successfully, and the unacceptably low overall survival rates mandate that we assess new potential therapies to ameliorate poor clinical response to conventional therapy. Abnormal tyrosine kinase activation in AML has been associated with poor prognosis and provides strategic targets for novel therapy development. We found that Mer receptor tyrosine kinase was over-expressed in a majority of pediatric (29/36, 80%) and adult (10/10, 100%) primary AML patient blasts at the time of diagnosis, and 100% of patient samples at the time of relapse. Mer was also found to be expressed in 12 of 14 AML cell lines (86%). In contrast, normal bone marrow myeloid precursors expressed little to no Mer. Following AML cell line stimulation with Gas6, a Mer ligand, we observed activation of prosurvival and proliferative signaling pathways, including phosphorylation of ERK1/2, p38, MSK1, CREB, ATF1, AKT and STAT6. To assess the phenotypic role of Mer in AML, two independent short-hairpin RNA (shRNA) constructs were used to decrease Mer expression in the AML cell lines Nomo-1 and Kasumi-1. Reduction of Mer protein levels significantly increased rates of myeloblast apoptosis two to threefold in response to serum starvation. Furthermore, myeloblasts with knocked-down Mer demonstrated decreased colony formation by 67–87%, relative to control cell lines (P<0.01). NOD-SCID-gamma mice transplanted with Nomo-1 myeloblasts with reduced levels of Mer had a significant prolongation in survival compared with mice transplanted with the parental or control cell lines (median survival 17 days in parental and control cell lines, versus 32–36 days in Mer knockdown cell lines, P<0.0001). These data suggest a role for Mer in acute myeloid leukemogenesis and indicate that targeted inhibition of Mer may be an effective therapeutic strategy in pediatric and adult AML. PMID:23474756

  13. Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia.

    PubMed

    Lee-Sherick, A B; Eisenman, K M; Sather, S; McGranahan, A; Armistead, P M; McGary, C S; Hunsucker, S A; Schlegel, J; Martinson, H; Cannon, C; Keating, A K; Earp, H S; Liang, X; DeRyckere, D; Graham, D K

    2013-11-14

    Acute myeloid leukemia (AML) continues to be extremely difficult to treat successfully, and the unacceptably low overall survival rates mandate that we assess new potential therapies to ameliorate poor clinical response to conventional therapy. Abnormal tyrosine kinase activation in AML has been associated with poor prognosis and provides strategic targets for novel therapy development. We found that Mer receptor tyrosine kinase was over-expressed in a majority of pediatric (29/36, 80%) and adult (10/10, 100%) primary AML patient blasts at the time of diagnosis, and 100% of patient samples at the time of relapse. Mer was also found to be expressed in 12 of 14 AML cell lines (86%). In contrast, normal bone marrow myeloid precursors expressed little to no Mer. Following AML cell line stimulation with Gas6, a Mer ligand, we observed activation of prosurvival and proliferative signaling pathways, including phosphorylation of ERK1/2, p38, MSK1, CREB, ATF1, AKT and STAT6. To assess the phenotypic role of Mer in AML, two independent short-hairpin RNA (shRNA) constructs were used to decrease Mer expression in the AML cell lines Nomo-1 and Kasumi-1. Reduction of Mer protein levels significantly increased rates of myeloblast apoptosis two to threefold in response to serum starvation. Furthermore, myeloblasts with knocked-down Mer demonstrated decreased colony formation by 67-87%, relative to control cell lines (P<0.01). NOD-SCID-gamma mice transplanted with Nomo-1 myeloblasts with reduced levels of Mer had a significant prolongation in survival compared with mice transplanted with the parental or control cell lines (median survival 17 days in parental and control cell lines, versus 32-36 days in Mer knockdown cell lines, P<0.0001). These data suggest a role for Mer in acute myeloid leukemogenesis and indicate that targeted inhibition of Mer may be an effective therapeutic strategy in pediatric and adult AML. PMID:23474756

  14. MERS-CoV in a healthcare worker in Jeddah, Saudi Arabia: an index case investigation.

    PubMed

    Shalhoub, S; Abdraboh, S; Palma, R; AlSharif, H; Assiri, N

    2016-07-01

    In September 2015, a confirmed case of Middle East respiratory syndrome (MERS) was diagnosed in a healthcare worker in Jeddah, Saudi Arabia. Given the absence of confirmed MERS cases in Jeddah at the time, an epidemiological index case investigation took place. The investigation identified a probable source of an index case who had been in hospital in Jordan in August 2015 while there was an ongoing MERS outbreak and who then subsequently sought medical care in Jeddah. PMID:27210272

  15. Disk-based k-mer counting on a PC

    PubMed Central

    2013-01-01

    Background The k-mer counting problem, which is to build the histogram of occurrences of every k-symbol long substring in a given text, is important for many bioinformatics applications. They include developing de Bruijn graph genome assemblers, fast multiple sequence alignment and repeat detection. Results We propose a simple, yet efficient, parallel disk-based algorithm for counting k-mers. Experiments show that it usually offers the fastest solution to the considered problem, while demanding a relatively small amount of memory. In particular, it is capable of counting the statistics for short-read human genome data, in input gzipped FASTQ file, in less than 40 minutes on a PC with 16 GB of RAM and 6 CPU cores, and for long-read human genome data in less than 70 minutes. On a more powerful machine, using 32 GB of RAM and 32 CPU cores, the tasks are accomplished in less than half the time. No other algorithm for most tested settings of this problem and mammalian-size data can accomplish this task in comparable time. Our solution also belongs to memory-frugal ones; most competitive algorithms cannot efficiently work on a PC with 16 GB of memory for such massive data. Conclusions By making use of cheap disk space and exploiting CPU and I/O parallelism we propose a very competitive k-mer counting procedure, called KMC. Our results suggest that judicious resource management may allow to solve at least some bioinformatics problems with massive data on a commodity personal computer. PMID:23679007

  16. Planetary GIS on the Web for the MER 2003 Landers

    NASA Astrophysics Data System (ADS)

    Hare, T. M.; Tanaka, K. L.; Skinner, J. A.

    2001-01-01

    PIGWAD or "Planetary Interactive GIS-on-the-Web Analyzable Database," has been operational since May of 1999. It currently provides GIS database support for the research and academic planetary science communities. We are now focused on creating a Mars Exploration Rover (MER) web-based landing-site analysis page. Along with the NASA Ames Research Center's web site, the PIGWAD web server also contains mission information including engineering constraints. The marriage of these two web sites gives scientists a great resource of information to analyze for landing-site selection.

  17. Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein.

    PubMed

    Xia, Shuai; Liu, Qi; Wang, Qian; Sun, Zhiwu; Su, Shan; Du, Lanying; Ying, Tianlei; Lu, Lu; Jiang, Shibo

    2014-12-19

    The recent outbreak of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) infection has led to more than 800 laboratory-confirmed MERS cases with a high case fatality rate (∼35%), posing a serious threat to global public health and calling for the development of effective and safe therapeutic and prophylactic strategies to treat and prevent MERS-CoV infection. Here we discuss the most recent studies on the structure of the MERS-CoV spike protein and its role in virus binding and entry, and the development of MERS-CoV entry/fusion inhibitors targeting the S1 subunit, particularly the receptor-binding domain (RBD), and the S2 subunit, especially the HR1 region, of the MERS-CoV spike protein. We then look ahead to future applications of these viral entry/fusion inhibitors, either alone or in combination with specific and nonspecific MERS-CoV replication inhibitors, for the treatment and prevention of MERS-CoV infection. PMID:25451066

  18. CoMeta: classification of metagenomes using k-mers.

    PubMed

    Kawulok, Jolanta; Deorowicz, Sebastian

    2015-01-01

    Nowadays, the study of environmental samples has been developing rapidly. Characterization of the environment composition broadens the knowledge about the relationship between species composition and environmental conditions. An important element of extracting the knowledge of the sample composition is to compare the extracted fragments of DNA with sequences derived from known organisms. In the presented paper, we introduce an algorithm called CoMeta (Classification of metagenomes), which assigns a query read (a DNA fragment) into one of the groups previously prepared by the user. Typically, this is one of the taxonomic rank (e.g., phylum, genus), however prepared groups may contain sequences having various functions. In CoMeta, we used the exact method for read classification using short subsequences (k-mers) and fast program for indexing large set of k-mers. In contrast to the most popular methods based on BLAST, where the query is compared with each reference sequence, we begin the classification from the top of the taxonomy tree to reduce the number of comparisons. The presented experimental study confirms that CoMeta outperforms other programs used in this context. CoMeta is available at https://github.com/jkawulok/cometa under a free GNU GPL 2 license. PMID:25884504

  19. CoMeta: Classification of Metagenomes Using k-mers

    PubMed Central

    Kawulok, Jolanta; Deorowicz, Sebastian

    2015-01-01

    Nowadays, the study of environmental samples has been developing rapidly. Characterization of the environment composition broadens the knowledge about the relationship between species composition and environmental conditions. An important element of extracting the knowledge of the sample composition is to compare the extracted fragments of DNA with sequences derived from known organisms. In the presented paper, we introduce an algorithm called CoMeta (Classification of metagenomes), which assigns a query read (a DNA fragment) into one of the groups previously prepared by the user. Typically, this is one of the taxonomic rank (e.g., phylum, genus), however prepared groups may contain sequences having various functions. In CoMeta, we used the exact method for read classification using short subsequences (k-mers) and fast program for indexing large set of k-mers. In contrast to the most popular methods based on BLAST, where the query is compared with each reference sequence, we begin the classification from the top of the taxonomy tree to reduce the number of comparisons. The presented experimental study confirms that CoMeta outperforms other programs used in this context. CoMeta is available at https://github.com/jkawulok/cometa under a free GNU GPL 2 license. PMID:25884504

  20. mer and fac isomerism in tris chelate diimine metal complexes.

    PubMed

    Dabb, Serin L; Fletcher, Nicholas C

    2015-03-14

    In this perspective, we highlight the issue of meridional (mer) and facial (fac) orientation of asymmetrical diimines in tris-chelate transition metal complexes. Diimine ligands have long been the workhorse of coordination chemistry, and whilst there are now good strategies to isolate materials where the inherent metal centered chirality is under almost complete control, and systematic methodologies to isolate heteroleptic complexes, the conceptually simple geometrical isomerism has not been widely investigated. In systems where the two donor atoms are significantly different in terms of the σ-donor and π-accepting ability, the fac isomer is likely to be the thermodynamic product. For the diimine complexes with two trigonal planar nitrogen atoms there is much more subtlety to the system, and external factors such as the solvent, lattice packing and the various steric considerations play a delicate role in determining the observed and isolable product. In this article we discuss the possibilities to control the isomeric ratio in labile systems, consider the opportunities to separate inert complexes and discuss the observed differences in their spectroscopic properties. Finally we report on the ligand orientation in supramolecular systems where facial coordination leads to simple regular structures such as helicates and tetrahedra, but the ability of the ligand system to adopt a mer orientation enables self-assembled structures of considerable beauty and complexity. PMID:25600485

  1. Overlapping MERS and mild AESD caused by HHV-6 infection.

    PubMed

    Hatanaka, Mari; Kashiwagi, Mitsuru; Tanabe, Takuya; Nakahara, Hiroshi; Ohta, Kazumi; Tamai, Hiroshi

    2015-03-01

    We report the case of an overlapping encephalopathy syndrome consisting of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) caused by human herpesvirus-6. A previously healthy 17-month-old girl was admitted to our hospital as a precaution because of seizures that had developed more than 25 hours (h) after fever. Brain diffusion-weighted images (DWI) showed high signal intensity in the central splenial region on Day 2. She regained consciousness 16 h after the second seizure. On Day 6, she had a secondary cluster of partial seizures. DWI showed resolution of the splenial lesion and revealed reduced diffusion in the fronto-subcortical white matter. She regained consciousness 36 h after the secondary cluster of seizures without any sequelae. A third DWI performed on Day 15 showed that the fronto-subcortical white matter lesions had completely disappeared. Based on the clinicoradiological findings, we diagnosed the patient with overlapping MERS and mild AESD. Our case, together with previous reports, suggests that patients can develop combined encephalopathy syndromes as a phenotype. Many encephalopathy syndromes have been established and classified; however, some may not present as independent syndromes. PMID:24856142

  2. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction.

    PubMed

    Omrani, Ali S; Al-Tawfiq, Jaffar A; Memish, Ziad A

    2015-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine. PMID:26924345

  3. Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR

    PubMed Central

    Chang, Chih-Chiang; Lin, Li-Ying; Zou, Xiao-Wei; Huang, Chieh-Chen; Chan, Nei-Li

    2015-01-01

    The mer operon confers bacterial resistance to inorganic mercury (Hg2+) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg2+-binding. To understand how MerR interacts with Hg2+ and how Hg2+-binding modulates MerR function, we report here the crystal structures of apo and Hg2+-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg2+-MerR structure offers the first view of a triligated Hg2+-thiolate center in a metalloprotein, confirming that MerR binds Hg2+ via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg2+ binding site, thereby providing a structural basis for the Hg2+-mediated functional switching of MerR. The pronounced Hg2+-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon. PMID:26150423

  4. MERS epidemiological investigation to detect potential mode of transmission in the 178th MERS confirmed case in Pyeongtaek, Korea

    PubMed Central

    Chang, Kyujin; Ki, Moran; Lee, Eun Gyu; Lee, Soon Young; Yoo, Byoungin; Choi, Jong Hyuk

    2015-01-01

    Most cases of Middle East Respiratory Syndrome (MERS) infection in Korea (outbreak: May 11-July 4, 2015) occurred in hospital settings, with uncertain transmission modes in some cases. We performed an in-depth investigation epidemiological survey on the 178th case to determine the precise mode of transmission. A 29- year-old man living in Pyeongtaek presented on June 16 with a febrile sensation, chills, and myalgia. Upon confirmatory diagnosis on June 23, he was treated in an isolation room and discharged on July 2 after cure. An epidemiological investigation of all possible infection routes indicated two likely modes of transmission: exposure to MERS in Pyeongtaek St. Mary’s Hospital during a visit to his hospitalized father (May 18-29), and infection through frequent contact with his father between the latter’s referral to Pyeongtaek Good Samaritan Bagae Hospital for treatment without confirmatory diagnosis until his death (May 29-June 6). Although lack of clear proof or evidence to the contrary does not allow a definitive conclusion, all other possibilities could be excluded by epidemiological inferences. While it is impossible to trace back the modes of transmission of all cases in a large-scale outbreak, case-by-case tracking and isolation of infected individuals and those in close contact with them is important in preventing the spread. Efforts should be made to establish a methodology for rapid tracking of all possible contacts and elimination-based identification of the precise modes of transmission. PMID:26493651

  5. Knowledge and Apprehension of Dental Patients about MERS-A Questionnaire Survey

    PubMed Central

    Ashok, Nipun; Rodrigues, Jean Clare; Azouni, Khalid; Darwish, Shorouk; Abuderman, Abdulwahab; Alkaabba, Abdul Aziz Fahad

    2016-01-01

    Introduction Middle East Respiratory Syndrome (MERS) is a disease caused by beta corona virus. From April 11th to 9th June 2014, World Health Organization (WHO) reported a total of 402 laboratory confirmed cases of MERS from KSA, out of which 132 cases were reported from Riyadh alone. Aim The aim of this study was to assess the knowledge and apprehension of patients about MERS visiting Al Farabi College of Dentistry, Riyadh, Saudi Arabia. Materials and Methods A cross-sectional questionnaire based survey was conducted which consisted of 10 self-prepared questions. A total of 404 patients participated in this study. Results Three hundred and forty patients had heard about MERS. Nearly a quarter of the patients (25.74%) were apprehensive about undergoing dental treatment because of MERS. A little more than half of the patients (50.99%) knew that camel was a source of Middle East Respiratory Syndrome-Corona virus. Most of the patients (80.72%) were aware of the infection control measures to be followed by dentist and 138 patients claimed they took some precaution when present inside the dental college. Conclusion Majority of the patients had heard about MERS and was aware of the infection control measures. However, some patients were apprehensive about undergoing dental treatment because of MERS. Further steps need to be taken to educate the patient’s about transmission of MERS and infection control measures in a dental hospital. PMID:27437361

  6. Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission

    PubMed Central

    Zhang, Zhao; Shen, Libing; Gu, Xun

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human. PMID:27142087

  7. 19F-NMR reveals metal and operator-induced allostery in MerR.

    PubMed

    Song, Lingyun; Teng, Quincy; Phillips, Robert S; Brewer, John M; Summers, Anne O

    2007-08-01

    Metalloregulators of the MerR family activate transcription upon metal binding by underwinding the operator-promoter DNA to permit open complex formation by pre-bound RNA polymerase. Historically, MerR's allostery has been monitored only indirectly via nuclease sensitivity or by fluorescent nucleotide probes and was very specific for Hg(II), although purified MerR binds several thiophilic metals. To observe directly MerR's ligand-induced behavior we made 2-fluorotyrosine-substituted MerR and found similar, minor changes in (19)F chemical shifts of tyrosine residues in the free protein exposed to Hg(II), Cd(II) or Zn(II). However, DNA binding elicits large chemical shift changes in MerR's tyrosine residues and in DNA-bound MerR Hg(II) provokes changes very distinct from those of Cd(II) or Zn(II). These chemical shift changes and other biophysical and phenotypic properties of wild-type MerR and relevant mutants reveal elements of an allosteric network that enables the coordination state of the metal binding site to direct metal-specific movements in the distant DNA binding site and the DNA-bound state also to affect the metal binding domain. PMID:17560604

  8. Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East.

    PubMed

    Carias, Cristina; O'Hagan, Justin J; Jewett, Amy; Gambhir, Manoj; Cohen, Nicole J; Haber, Yoni; Pesik, Nicki; Swerdlow, David L

    2016-04-01

    In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region. PMID:27358972

  9. Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East

    PubMed Central

    O’Hagan, Justin J.; Jewett, Amy; Gambhir, Manoj; Cohen, Nicole J.; Haber, Yoni; Pesik, Nicki; Swerdlow, David L.

    2016-01-01

    In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region. PMID:27358972

  10. Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission.

    PubMed

    Zhang, Zhao; Shen, Libing; Gu, Xun

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV's evolutionary history and the positive selection sites in MERS-CoV's S protein might enable it to infect human. PMID:27142087

  11. The Mars Exploration Rover (MER) Transverse Impulse Rocket System (TIRS)

    NASA Technical Reports Server (NTRS)

    SanMartin, Alejandro Miguel; Bailey, Erik

    2005-01-01

    In a very short period of time the MER project successfully developed and tested a system, TIRS/DIMES, to improve the probability of success in the presence of large Martian winds. The successful development of TIRS/DIMES played a big role in the landing site selection process by enabling the landing of Spirit on Gusev crater, a site of very high scientific interest but with known high wind conditions. The performance of TIRS by Spirit at Gusev Crater was excellent. The velocity prediction error was small and Big TIRS was fired reducing the impact horizontal velocity from approximately 23 meters per second to approximately 11 meters per second, well within the airbag capabilities. The performance of TIRS by Opportunity at Meridiani was good. The velocity prediction error was rather large (approximately 6 meters per second, a less than 2 sigma value, but TIRS did not fire which was the correct action.

  12. MER-DIMES : a planetary landing application of computer vision

    NASA Technical Reports Server (NTRS)

    Cheng, Yang; Johnson, Andrew; Matthies, Larry

    2005-01-01

    During the Mars Exploration Rovers (MER) landings, the Descent Image Motion Estimation System (DIMES) was used for horizontal velocity estimation. The DIMES algorithm combines measurements from a descent camera, a radar altimeter and an inertial measurement unit. To deal with large changes in scale and orientation between descent images, the algorithm uses altitude and attitude measurements to rectify image data to level ground plane. Feature selection and tracking is employed in the rectified data to compute the horizontal motion between images. Differences of motion estimates are then compared to inertial measurements to verify correct feature tracking. DIMES combines sensor data from multiple sources in a novel way to create a low-cost, robust and computationally efficient velocity estimation solution, and DIMES is the first use of computer vision to control a spacecraft during planetary landing. In this paper, the detailed implementation of the DIMES algorithm and the results from the two landings on Mars are presented.

  13. MER : from landing to six wheels on Mars ... twice

    NASA Technical Reports Server (NTRS)

    Krajewski, Joel; Burke, Kevin; Lewicki, Chris; Limonadi, Daniel; Trebi-Ollennu, Ashitey; Voorhees, Chris

    2005-01-01

    Application of the Pathfinder landing system design to enclose the much larger Mars Exploration Rover required a variety of Rover deployments to achieve the surface driving configuration. The project schedule demanded that software design, engineering model test, and flight hardware build to be accomplished in parallel. This challenge was met through (a) bounding unknown environments against which to design and test, (b) early mechanical prototype testing, (c) constraining the scope of on-board autonomy to survival-critical deployments, (d) executing a balance of nominal and off-nominal test cases, (e) developing off-nominal event mitigation techniques before landing, (f) flexible replanning in response to surprises during operations. Here is discussed several specific events encountered during initial MER surface operations.

  14. MERS and the dromedary camel trade between Africa and the Middle East.

    PubMed

    Younan, M; Bornstein, S; Gluecks, I V

    2016-08-01

    Dromedary camels are the most likely source for the coronavirus that sporadically causes Middle East respiratory syndrome (MERS) in humans. Serological results from archived camel sera provide evidence for circulation of MERS coronavirus (MERS-CoV) among dromedary camels in the Greater Horn of Africa as far back as 1983 and in Saudi Arabia as far back as 1992. High seroprevalences of MERS-CoV antibodies and the high virus prevalence in Saudi Arabian dromedary camels indicate an endemicity of the virus in the Arabian Peninsula, which predates the 2012 human MERS index case. Saudi Arabian dromedary camels show significantly higher MERS-CoV carrier rates than dromedary camels imported from Africa. Two MERS-CoV lineages identified in Nigerian camels were found to be genetically distinct from those found in camels and humans in the Middle East. This supports the hypothesis that camel imports from Africa are not of significance for circulation of the virus in camel populations of the Arabian Peninsula. PMID:27324244

  15. Sero-epidemiology of MERS coronavirus in Saudi Arabia (1993) and Australia (2014) and characterization of assay specificity

    PubMed Central

    Hemida, MG; Perera, RAPM; Al Jassim, RAM; Kayali, G; Siu, LY; Wang, P; Chu, DKW; Perlman, S; Ali, MA; Alnaeem, A; Poon, LLM; Saif, L; Peiris, M

    2015-01-01

    Pseudoparticle virus neutralization (ppNT) and a conventional microneutralization (MN) assays are specific for detecting antibodies to MERS coronavirus (MERS-CoV) when used in sero-epidemiological studies in animals. Genetically diverse MERS-CoV appear antigenically similar in MN tests. We confirm that MERS-CoV has been circulating in dromedaries in Saudi Arabia in 1993. Preliminary data suggests that feral Australian dromedaries may be free of MERS-CoV but larger confirmatory studies are needed. PMID:24957744

  16. Opposing Roles of Tyrosine Kinase Receptors Mer and Axl Determine Clinical Outcomes in Experimental Immune-Mediated Nephritis.

    PubMed

    Zhen, Yuxuan; Priest, Stephen O; Shao, Wen-Hai

    2016-09-15

    Glomerulonephritis is one of the most severe manifestations of systemic lupus erythematosus, with considerable morbidity and mortality. There remains a major unmet need for successful management of lupus nephritis. TAM family receptor tyrosine kinases (Mer and Axl) play an important role in the maintenance of immune homeostasis in the kidney. Mer is constitutively expressed in the glomeruli; Axl expression is inducible in glomeruli under inflammatory conditions. To investigate the distinct functions of Axl and Mer in lupus nephritis, we compared the severity of nephrotoxic serum glomerulonephritis in wild-type (WT), Axl-knockout (KO), Mer-KO, and Axl/Mer-KO mice. Mer-KO mice developed severe glomerulonephritis, with significantly decreased survival and increased blood urea nitrogen levels compared with WT mice given the same treatment. However, nephrotoxic serum-treated Axl-KO mice had significantly increased survival rates and improved renal function compared with similarly treated WT, Mer-KO, and Axl/Mer-KO mice. Interestingly, mice lacking both Axl and Mer developed kidney inflammation comparable to WT mice. Western blot analysis revealed significantly increased Stat3 phosphorylation and caspase-1 activation in the kidneys of nephritic Mer-KO mice. In contrast, Axl-deficient nephrotoxic serum-injected mice showed decreased Akt phosphorylation and Bcl-xL upregulation. Thus, the reciprocal activation of Axl and Mer receptor tyrosine kinases has a major impact on the outcome of renal inflammation. PMID:27527599

  17. Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection.

    PubMed

    Houser, Katherine V; Gretebeck, Lisa; Ying, Tianlei; Wang, Yanping; Vogel, Leatrice; Lamirande, Elaine W; Bock, Kevin W; Moore, Ian N; Dimitrov, Dimiter S; Subbarao, Kanta

    2016-05-15

    With >1600 documented human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) and a case fatality rate of approximately 36%, medical countermeasures are needed to prevent and limit the disease. We examined the in vivo efficacy of the human monoclonal antibody m336, which has high neutralizing activity against MERS-CoV in vitro. m336 was administered to rabbits intravenously or intranasally before infection with MERS-CoV. Prophylaxis with m336 resulted in a reduction of pulmonary viral RNA titers by 40-9000-fold, compared with an irrelevant control antibody with little to no inflammation or viral antigen detected. This protection in rabbits supports further clinical development of m336. PMID:26941283

  18. Planning Mars Memory: Learning from the Mer Mission

    NASA Technical Reports Server (NTRS)

    Linde, Charlotte

    2004-01-01

    Knowledge management for space exploration is part of a multi-generational effort at recognizing, preserving and transmitting learning. Each mission should be built on the learning, of both successes and failures, derived from previous missions. Knowledge management begins with learning, and the recognition that this learning has produced knowledge. The Mars Exploration Rover mission provides us with an opportunity to track how learning occurs, how it is recorded, and whether the representations of this learning will be optimally useful for subsequent missions. This paper focuses on the MER science and engineering teams during Rover operations. A NASA team conducted an observational study of the ongoing work and learning of the these teams. Learning occurred in a wide variety of areas: how to run two teams on Mars time for three months; how to use the instruments within the constraints of the martian environment, the deep space network and the mission requirements; how to plan science strategy; how best to use the available software tools. This learning is preserved in many ways. Primarily it resides in peoples memories, to be carried on to the next mission. It is also encoded in stones, in programming sequences, in published reports, and in lessons learned activities, Studying learning and knowledge development as it happens allows us to suggest proactive ways of capturing and using it across multiple missions and generations.

  19. Water on Mars: Evidence from MER Mission Results

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    2004-01-01

    The Viking and the Mars Exploration Rover missions observed that the surface of Mars is encrusted by a thinly cemented layer, or "duricrust". Elemental analyzes at five sites on Mars show that these soils have sulfur content and chlorine content consistent with the presence of sulfates and halides as mineral cements. The soil is highly enriched in the salt-forming elements compared with rock. Analysis of the soil cementation indicates some features which may be evidence of liquid water. At both MER sites, duricrust textures revealed by the Microscopic Imager show features including the presence of fine sand-sized grains, some of which may be aggregates of fine silt and clay, surrounded by a pervasive light colored material that is associated with microtubular structures and networks of microfractures. Stereo views of undisturbed duricrust surfaces reveal rugged microrelief between 2-3 mm and minimal loose material. Comparisons of microscopic images of duricrust soils obtain before and after placement of the Mossbauer spectrometer indicate differing degrees of compaction and cementation. Two models of a transient water hypothesis are offered, a "top down" hypothesis that emphasizes the surface deposition of frost, melting and downward migration of liquid water and a "bottom up" alternative that proposes the presence of interstitial ice/brine, with the upward capillary migration of liquid water. The viability of both of these models ultimately hinges on the availability of seasonally transient liquid water for brief periods.

  20. Redefining Tactical Operations for MER Using Cloud Computing

    NASA Technical Reports Server (NTRS)

    Joswig, Joseph C.; Shams, Khawaja S.

    2011-01-01

    The Mars Exploration Rover Mission (MER) includes the twin rovers, Spirit and Opportunity, which have been performing geological research and surface exploration since early 2004. The rovers' durability well beyond their original prime mission (90 sols or Martian days) has allowed them to be a valuable platform for scientific research for well over 2000 sols, but as a by-product it has produced new challenges in providing efficient and cost-effective tactical operational planning. An early stage process adaptation was the move to distributed operations as mission scientists returned to their places of work in the summer of 2004, but they would still came together via teleconference and connected software to plan rover activities a few times a week. This distributed model has worked well since, but it requires the purchase, operation, and maintenance of a dedicated infrastructure at the Jet Propulsion Laboratory. This server infrastructure is costly to operate and the periodic nature of its usage (typically heavy usage for 8 hours every 2 days) has made moving to a cloud based tactical infrastructure an extremely tempting proposition. In this paper we will review both past and current implementations of the tactical planning application focusing on remote plan saving and discuss the unique challenges present with long-latency, distributed operations. We then detail the motivations behind our move to cloud based computing services and as well as our system design and implementation. We will discuss security and reliability concerns and how they were addressed

  1. Autonomous Navigation Results from the Mars Exploration Rover (MER) Mission

    NASA Technical Reports Server (NTRS)

    Maimone, Mark; Johnson, Andrew; Cheng, Yang; Willson, Reg; Matthies, Larry H.

    2004-01-01

    In January, 2004, the Mars Exploration Rover (MER) mission landed two rovers, Spirit and Opportunity, on the surface of Mars. Several autonomous navigation capabilities were employed in space for the first time in this mission. ]n the Entry, Descent, and Landing (EDL) phase, both landers used a vision system called the, Descent Image Motion Estimation System (DIMES) to estimate horizontal velocity during the last 2000 meters (m) of descent, by tracking features on the ground with a downlooking camera, in order to control retro-rocket firing to reduce horizontal velocity before impact. During surface operations, the rovers navigate autonomously using stereo vision for local terrain mapping and a local, reactive planning algorithm called Grid-based Estimation of Surface Traversability Applied to Local Terrain (GESTALT) for obstacle avoidance. ]n areas of high slip, stereo vision-based visual odometry has been used to estimate rover motion, As of mid-June, Spirit had traversed 3405 m, of which 1253 m were done autonomously; Opportunity had traversed 1264 m, of which 224 m were autonomous. These results have contributed substantially to the success of the mission and paved the way for increased levels of autonomy in future missions.

  2. Nutrient availability at Mer Bleue bog measured by PRSTM probes

    NASA Astrophysics Data System (ADS)

    Wang, M.; Moore, T. R.; Talbot, J.

    2015-12-01

    Bogs, covering ~0.7 million km2 in Canada, store a large amount of C and N. As nutrient deficient ecosystems, it's critical to examine the nutrient availabilities and seasonal dynamics. We used Plant Root Simulators (PRSTM) at Mer Bleue bog to provide some baseline data on nutrient availability and its variability. In particular, we focused on ammonium, nitrate, phosphate, calcium, magnesium and potassium, iron, sulphate and aluminum. We placed PRS probes at a depth of 5 - 15 cm in pristine plots and plots with long term N, P and K fertilization for 4 weeks and determined the availability of these nutrients, from spring through to fall. Probes were also placed beneath the water table in hummock and hollow microtopography and along a transect including part of the bog which had been drained through the creation of a ditch 80 years ago. The result showed that there was limited available ammonium, nitrate and phosphate in the bog, the seasonal variation of nutrient availabilities probably due to mineralization, an increase in the availability of some nutrients between different water table depths or as a result of drainage, and the relative availability of nutrients compared to the input from fertilization. We suggest that PRS probes could be a useful tool to examine nutrient availability and dynamics in wetlands, with careful consideration of installing condition, for example, proper exposure period, depth relative to water table etc.

  3. China upgrades surveillance and control measures of Middle East respiratory syndrome (MERS).

    PubMed

    Gao, Jianjun; Song, Peipei

    2015-06-01

    Three years after the identification of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, the first case of MERS in China was reported on May 29, 2015. Although the Chinese government issued the MERS Prevention and Control Plan in 2013, a novel edition was released on June 5, 2015 to better cope with the current epidemic situation. The revised Plan refines the descriptions in case-finding and establishment of case-monitoring systems. In addition, tougher regulations on close contacts of confirmed patients and suspected cases are introduced in this new Plan. It is expected these countermeasures will play a greater role in surveilling and controlling MERS in China. PMID:26063202

  4. Lessons to learn from MERS-CoV outbreak in South Korea.

    PubMed

    Khan, Adnan; Farooqui, Amber; Guan, Yi; Kelvin, David J

    2015-06-01

    Since the first identification of Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) in 2012 the virus has infected 1289 humans with approximately 40% mortalities. Currently South Korea is experiencing the hospital-associated outbreak of MER-CoV that has infected 126 human cases and 13 deaths, as of 12 June 2015, following the return of a MERS infected patient from Middle East. The episode is characterized unique being the largest cluster of patients linked to the single introduction of virus that involves three generations of virus transmission. Human-to-human transmission though was observed on several occasions in past, it is documented as non-sustainable event. The recent outbreak including the healthcare workers, index case's roommates and their caregivers, raises several concerns about the infection control practices and timely diagnosis of MERS. PMID:26142661

  5. Travel implications of emerging coronaviruses: SARS and MERS-CoV.

    PubMed

    Al-Tawfiq, Jaffar A; Zumla, Alimuddin; Memish, Ziad A

    2014-01-01

    The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and of the Middle East Syndrome Cornavirus (MERS-CoV) caused widespread fear and concern for their potential threat to global health security. There are similarities and differences in the epidemiology and clinical features between these two diseases. The origin of SARS-COV and MERS-CoV is thought to be an animal source with subsequent transmission to humans. The identification of both the intermediate host and the exact route of transmission of MERS-CoV is crucial for the subsequent prevention of the introduction of the virus into the human population. So far MERS-CoV had resulted in a limited travel-associated human cases with no major events related to the Hajj. PMID:25047726

  6. UNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

    PubMed Central

    2015-01-01

    We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined. PMID:25068800

  7. Health Care Associated Middle East Respiratory Syndrome (MERS): A Case from Iran

    PubMed Central

    Moniri, Afshin; Marjani, Majid; Tabarsi, Payam; Yadegarynia, Davood

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) Infection, has caused recurrent outbreaks worldwide. It is associated with severe morbidity and mortality, and is not treatable with the currently available antiviral therapies. We present a case of a 43 year-old male healthcare provider, who admitted with productive cough, dyspnea, myalgia, pleuritic chest pain and fever. Computed tomography (CT) showed bilateral ground glass opacities and consolidation. Sputum polymerase chain reaction (PCR) for MERS-coronavirus was positive. PMID:27114729

  8. Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013

    PubMed Central

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Watson, Simon J.; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend-Jan; Beer, Martin; Müller, Marcel A.; Kellam, Paul

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species transmission. Camels may act as a direct source of human MERS-CoV infection. PMID:24857749

  9. Genetic analysis of transcriptional activation and repression in the Tn21 mer operon. [Bacteria

    SciTech Connect

    Ross, W.; Park, S.J.; Summers, A.O. )

    1989-07-01

    Transcription of the Tn21 mercury resistance operon (mer) is controlled by the toxic metal cation Hg(II). This control is mediated by the product of the merR gene, a 144-amino-acid protein which represses transcription of the structural genes (merTPCAD) in the absence of Hg(II) and activates transcription in the presence of Hg(II). We have used a mer-lac transcriptional fusion to obtain regulatory mutants in this metal-responsive system. Some mutants were defective in Hg(II)-induced activation while retaining repression function, others were defective in repression but not activation, and some had lost both functions. Mutations in three of the four cysteine residues of merR resulted in complete loss of Hg(II)-inducible activation but retention of the repressor function. Other lesions adjacent to or very near these cysteines exhibited severely reduced activation and also retained repressor function. There were two putative helix-turn-helix (HTH) domains in merR, and mutants in each had very different phenotypes. A partially dominant mutation in the more amino-terminal region of the two putative HTH regions resulted in loss of both activation and repression, consistent with a role for this region in DNA binding. Mutations in the more centrally located HTH region resulted only in loss of Hg(II)-induced activation. Lesions in the central and in the carboxy-terminal regions of merR exhibited both Hg(II)-independent and Hg(II)-dependent transcriptional activation. The sole cis-acting mutant obtained with this operon fusion strategy, a down-promoter mutation, lies in a highly conserved base in the -35 region of the merTPCAD promoter.

  10. A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines

    PubMed Central

    Ma, Cuiqing; Tao, Xinrong; Wang, Lili; Zhao, Guangyu; Chen, Yaoqing; Yu, Fei; Tseng, Chien-Te K.; Zhou, Yusen; Jiang, Shibo

    2013-01-01

    An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection. PMID:24324708

  11. Middle East respiratory syndrome coronavirus "MERS-CoV": current knowledge gaps.

    PubMed

    Banik, G R; Khandaker, G; Rashid, H

    2015-06-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) that causes a severe lower respiratory tract infection in humans is now considered a pandemic threat to the Gulf region. Since its discovery in 2012, MERS-CoV has reached 23 countries affecting about 1100 people, including a dozen children, and claiming over 400 lives. Compared to SARS (severe acute respiratory syndrome), MERS-CoV appears to kill more people (40% versus 10%), more quickly, and is especially more severe in those with pre-existing medical conditions. Most MERS-CoV cases (>85%) reported thus far have a history of residence in, or travel to the Middle East. The current epidemiology is characterised by slow and sustained transmission with occasional sparks. The dromedary camel is the intermediate host of MERS-CoV, but the transmission cycle is not fully understood. In this current review, we have briefly summarised the latest information on the epidemiology, clinical features, diagnosis, treatment and prevention of MERS-CoV especially highlighting the knowledge gaps in its transmission dynamics, diagnosis and preventive strategy. PMID:26002405

  12. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus

    PubMed Central

    Corti, Davide; Zhao, Jincun; Pedotti, Mattia; Simonelli, Luca; Agnihothram, Sudhakar; Fett, Craig; Fernandez-Rodriguez, Blanca; Foglierini, Mathilde; Agatic, Gloria; Vanzetta, Fabrizia; Gopal, Robin; Langrish, Christopher J.; Barrett, Nicholas A; Sallusto, Federica; Baric, Ralph S.; Varani, Luca; Zambon, Maria; Perlman, Stanley; Lanzavecchia, Antonio

    2015-01-01

    Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses. PMID:26216974

  13. Middle East respiratory syndrome coronavirus (MERS-CoV): prevention in travelers.

    PubMed

    Pavli, Androula; Tsiodras, Sotirios; Maltezou, Helena C

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), a novel coronavirus that causes a severe lower respiratory tract infection in humans, emerged in the Middle East in 2012. Since then, MERS-CoV has caused an ongoing epidemic in the Arabian Peninsula with sporadic cases imported in Europe, North Africa, Southeast Asia, and the United States of America. As of 28th May 2014, 636 laboratory-confirmed cases of infection with MERS-CoV have been reported to World Health Organization including 14 cases imported by travelers. The epicenter of the current MERS-CoV epidemic is located in Saudi Arabia, where millions of pilgrims travel for two mass gatherings annually. In this review we summarize MERS-CoV cases in relation to travel with focus on the epidemiology and prevention in travelers. It is important to increase awareness of travelers about the risks and appropriate preventive measures and for health professionals to be on alert if a patient with severe respiratory symptoms reports a recent history of travel to the region affected with MERS-CoV. Measures should be taken by local health authorities of the affected countries in order to improve hospital hygiene. Finally, it is crucial to investigate the reasons for travelers' poor compliance with rules and recommendations issued by Saudi officials and to take appropriate measures in order to improve them. PMID:25457301

  14. Mer receptor tyrosine kinase is a therapeutic target in pre–B-cell acute lymphoblastic leukemia

    PubMed Central

    Linger, Rachel M. A.; Lee-Sherick, Alisa B.; DeRyckere, Deborah; Cohen, Rebecca A.; Jacobsen, Kristen M.; McGranahan, Amy; Brandão, Luis N.; Winges, Amanda; Sawczyn, Kelly K.; Liang, Xiayuan; Keating, Amy K.; Tan, Aik Choon; Earp, H. Shelton

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre–B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications. PMID:23861246

  15. Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute lymphoblastic leukemia.

    PubMed

    Linger, Rachel M A; Lee-Sherick, Alisa B; DeRyckere, Deborah; Cohen, Rebecca A; Jacobsen, Kristen M; McGranahan, Amy; Brandão, Luis N; Winges, Amanda; Sawczyn, Kelly K; Liang, Xiayuan; Keating, Amy K; Tan, Aik Choon; Earp, H Shelton; Graham, Douglas K

    2013-08-29

    Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications. PMID:23861246

  16. Challenges presented by MERS corona virus, and SARS corona virus to global health.

    PubMed

    Al-Hazmi, Ali

    2016-07-01

    Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections. PMID:27298584

  17. Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.

    PubMed

    Li, Nan; Liu, Zhenghui; Zhang, Yue; Chen, Qiaoyuan; Liu, Peng; Cheng, C Yan; Lee, Will M; Chen, Yongmei; Han, Daishu

    2015-03-01

    The mammalian testis is an immunoprivileged organ where male germ cell autoantigens are immunologically ignored. Both systemic immune tolerance to autoantigens and local immunosuppressive milieu contribute to the testicular immune privilege. Testicular immunosuppression has been intensively studied, but information on systemic immune tolerance to autoantigens is lacking. In the present study, we aimed to determine the role of Axl and Mer receptor tyrosine kinases in maintaining the systemic tolerance to male germ cell antigens using the experimental autoimmune orchitis (EAO) model. Axl and Mer double-knockout (Axl(-/-)Mer(-/-)) mice developed evident EAO after a single immunization with germ cell homogenates emulsified with complete Freund's adjuvant. EAO was characterized by the accumulation of macrophages and T lymphocytes in the testis. Damage to the seminiferous epithelium was also observed. EAO induction was associated with pro-inflammatory cytokine upregulation in the testes, impaired permeability of the blood-testis barrier and generation of autoantibodies against germ cell antigens in Axl(-/-)Mer(-/-) mice. Immunization also induced mild EAO in Axl or Mer single-gene-knockout mice. By contrast, a single immunization failed to induce EAO in wild-type mice. The results indicate that Axl and Mer receptors cooperatively regulate the systemic immune tolerance to male germ cell antigens. PMID:25403570

  18. Mer receptor tyrosine kinase mediates both tethering and phagocytosis of apoptotic cells

    PubMed Central

    Dransfield, I; Zagórska, A; Lew, E D; Michail, K; Lemke, G

    2015-01-01

    Billions of inflammatory leukocytes die and are phagocytically cleared each day. This regular renewal facilitates the normal termination of inflammatory responses, suppressing pro-inflammatory mediators and inducing their anti-inflammatory counterparts. Here we investigate the role of the receptor tyrosine kinase (RTK) Mer and its ligands Protein S and Gas6 in the initial recognition and capture of apoptotic cells (ACs) by macrophages. We demonstrate extremely rapid binding kinetics of both ligands to phosphatidylserine (PtdSer)-displaying ACs, and show that ACs can be co-opsonized with multiple PtdSer opsonins. We further show that macrophage phagocytosis of ACs opsonized with Mer ligands can occur independently of a requirement for αV integrins. Finally, we demonstrate a novel role for Mer in the tethering of ACs to the macrophage surface, and show that Mer-mediated tethering and subsequent AC engulfment can be distinguished by their requirement for Mer kinase activity. Our results identify Mer as a receptor uniquely capable of both tethering ACs to the macrophage surface and driving their subsequent internalization. PMID:25695599

  19. Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro)

    PubMed Central

    Tomar, Sakshi; Johnston, Melanie L.; St. John, Sarah E.; Osswald, Heather L.; Nyalapatla, Prasanth R.; Paul, Lake N.; Ghosh, Arun K.; Denison, Mark R.; Mesecar, Andrew D.

    2015-01-01

    All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CLpro) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CLpro from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CLpro is less efficient at processing a peptide substrate due to MERS-CoV 3CLpro being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CLpro enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CLpro is a weakly associated dimer (Kd ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CLpro were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CLpro undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CLpro from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CLpro dimerization. Activation of MERS-CoV 3CLpro through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CLpro inhibitors as antiviral agents. PMID:26055715

  20. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    PubMed Central

    Wei, Guo-Xian; Campagna, Alexander N; Bobek, Libuse A

    2007-01-01

    Background MUC7 12-mer (RKSYKCLHKRCR), a cationic antimicrobial peptide derived from the human low-molecular-weight salivary mucin MUC7, possesses potent antimicrobial activity in vitro. In order to evaluate the potential therapeutic application of the MUC7 12-mer, we examined the effects of mono- and divalent cations, EDTA, pH, and temperature on its antimicrobial activity. Methods Minimal Inhibitory Concentrations (MICs) were determined using a liquid growth inhibition assay in 96-well microtiter plates. MUC7 12-mer was added at concentrations of 1.56–50 μM. MICs were determined at three endpoints: MIC-0, MIC-1, and MIC-2 (the lowest drug concentration showing 10%, 25% and 50% of growth, respectively). To examine the effect of salts or EDTA, a checkerboard microdilution technique was used. Fractional inhibitory concentration index (FICi) was calculated on the basis of MIC-0. The viability of microbial cells treated with MUC7 12-mer in the presence of sodium or potassium was also determined by killing assay or flow cytometry. Results The MICs of MUC7 12-mer against organisms tested ranged from 6.25–50 μM. For C. albicans, antagonism (FICi 4.5) was observed for the combination of MUC7 12-mer and calcium; however, there was synergism (FICi 0.22) between MUC7 12-mer and EDTA, and the synergism was retained in the presence of calcium at its physiological concentration (1–2 mM). No antagonism but additivity or indifference (FICi 0.55–2.5) was observed for the combination of MUC7 12-mer and each K+, Na+, Mg2+, or Zn2+. MUC7 12-mer peptide (at 25 μM) also exerted killing activity in the presence of NaCl, (up to 25 mM for C. albicans and up to 150 mM for E. coli, a physiological concentration of sodium in the oral cavity and serum, respectively) and retained candidacidal activity in the presence of KCl (up to 40 mM). The peptide exhibited higher inhibitory activity against C. albicans at pH 7, 8, and 9 than at pH 5 and 6, and temperature up to 60°C did not

  1. Membrane topology of a 14-mer model amphipathic peptide: a solid-state NMR spectroscopy study.

    PubMed

    Ouellet, Marise; Doucet, Jean-Daniel; Voyer, Normand; Auger, Michèle

    2007-06-01

    We have investigated the interaction between a synthetic amphipathic 14-mer peptide and model membranes by solid-state NMR. The 14-mer peptide is composed of leucines and phenylalanines modified by the addition of crown ethers and forms a helical amphipathic structure in solution and bound to lipid membranes. To shed light on its membrane topology, 31P, 2H, 15N solid-state NMR experiments have been performed on the 14-mer peptide in interaction with mechanically oriented bilayers of dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), and dipalmitoylphosphatidylcholine (DPPC). The 31P, 2H, and 15N NMR results indicate that the 14-mer peptide remains at the surface of the DLPC, DMPC, and DPPC bilayers stacked between glass plates and perturbs the lipid orientation relative to the magnetic field direction. Its membrane topology is similar in DLPC and DMPC bilayers, whereas the peptide seems to be more deeply inserted in DPPC bilayers, as revealed by the greater orientational and motional disorder of the DPPC lipid headgroup and acyl chains. 15N{31P} rotational echo double resonance experiments have also been used to measure the intermolecular dipole-dipole interaction between the 14-mer peptide and the phospholipid headgroup of DMPC multilamellar vesicles, and the results indicate that the 14-mer peptide is in contact with the polar region of the DMPC lipids. On the basis of these studies, the mechanism of membrane perturbation of the 14-mer peptide is associated to the induction of a positive curvature strain induced by the peptide lying on the bilayer surface and seems to be independent of the bilayer hydrophobic thickness. PMID:17487978

  2. Biomolecular Mechanisms of Mercury Transfers and Transformations by Proteins of the Mer Operon

    NASA Astrophysics Data System (ADS)

    Miller, S. M.; Hong, B.; Nauss, R.; Momany, C.; Summers, A. O.; Feng, X.; Harwood, I.; Stroud, R.

    2008-12-01

    Aerobic bacteria exhibiting resistance to the toxic effects of Hg(II) and organomercurials [RHg(I), e.g. MeHg(I)] and are widely found in both pristine and mercury contaminated environments. Resistance, afforded by a plasmid- or transposon-associated mer operon, involves an unusual pathway where Hg(II) and organomercurials [RHg(I)] undergo facilitated entry into the bacterial cytoplasm via an integral membrane transport protein (MerT) and are then "detoxified" by the concerted effort of two enzymes, organomercurial lyase (MerB), which catalyzes dealkylation (i.e., demethylation) of RHg(I) to Hg(II) and a hydrocarbon, and mercuric ion reductase (MerA), which catalyzes reduction of Hg(II) to Hg(0) as the ultimate detoxification for the organism. With a widespread distribution, these bacterial transformations play a significant role in the fate of mercury in the environment. Our focus is on elucidation of the molecular mechanisms for the transport and catalytic transformations of RHg(I) and Hg(II) by these proteins and the factors that influence the overall efficiency of the process. Current efforts are focused primarily on elucidating details of RHg(I) binding and dealkylation by MerB as well as the mechanism for transfer of the Hg(II) product to MerA. Key findings include the demonstration of a non-cysteine residue as essential for the catalytic activity and demonstration that direct transfer of Hg(II) to MerA proceeds more rapidly and more completely than transfer to small MW thiols such as cysteines or glutathione. Reuslts of these studies as well as an overview of our current understanding of the whole system will be presented.

  3. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels.

    PubMed

    Haagmans, Bart L; van den Brand, Judith M A; Raj, V Stalin; Volz, Asisa; Wohlsein, Peter; Smits, Saskia L; Schipper, Debby; Bestebroer, Theo M; Okba, Nisreen; Fux, Robert; Bensaid, Albert; Solanes Foz, David; Kuiken, Thijs; Baumgärtner, Wolfgang; Segalés, Joaquim; Sutter, Gerd; Osterhaus, Albert D M E

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic MERS-CoV introductions from dromedary camels. In addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of MERS-CoV spread from the animal reservoir may be envisaged. Here we show that a modified vaccinia virus Ankara (MVA) vaccine expressing the MERS-CoV spike protein confers mucosal immunity in dromedary camels. Compared with results for control animals, we observed a significant reduction of excreted infectious virus and viral RNA transcripts in vaccinated animals upon MERS-CoV challenge. Protection correlated with the presence of serum neutralizing antibodies to MERS-CoV. Induction of MVA-specific antibodies that cross-neutralize camelpox virus would also provide protection against camelpox. PMID:26678878

  4. Rare k-mer DNA: Identification of sequence motifs and prediction of CpG island and promoter.

    PubMed

    Mohamed Hashim, Ezzeddin Kamil; Abdullah, Rosni

    2015-12-21

    Empirical analysis on k-mer DNA has been proven as an effective tool in finding unique patterns in DNA sequences which can lead to the discovery of potential sequence motifs. In an extensive study of empirical k-mer DNA on hundreds of organisms, the researchers found unique multi-modal k-mer spectra occur in the genomes of organisms from the tetrapod clade only which includes all mammals. The multi-modality is caused by the formation of the two lowest modes where k-mers under them are referred as the rare k-mers. The suppression of the two lowest modes (or the rare k-mers) can be attributed to the CG dinucleotide inclusions in them. Apart from that, the rare k-mers are selectively distributed in certain genomic features of CpG Island (CGI), promoter, 5' UTR, and exon. We correlated the rare k-mers with hundreds of annotated features using several bioinformatic tools, performed further intrinsic rare k-mer analyses within the correlated features, and modeled the elucidated rare k-mer clustering feature into a classifier to predict the correlated CGI and promoter features. Our correlation results show that rare k-mers are highly associated with several annotated features of CGI, promoter, 5' UTR, and open chromatin regions. Our intrinsic results show that rare k-mers have several unique topological, compositional, and clustering properties in CGI and promoter features. Finally, the performances of our RWC (rare-word clustering) method in predicting the CGI and promoter features are ranked among the top three, in eight of the CGI and promoter evaluations, among eight of the benchmarked datasets. PMID:26427337

  5. Comparison of De Novo Transcriptome Assemblers and k-mer Strategies Using the Killifish, Fundulus heteroclitus

    PubMed Central

    Rana, Satshil B.; Zadlock, Frank J.; Zhang, Ziping; Murphy, Wyatt R.; Bentivegna, Carolyn S.

    2016-01-01

    Background De novo assembly of non-model organism’s transcriptomes has recently been on the rise in concert with the number of de novo transcriptome assembly software programs. There is a knowledge gap as to what assembler software or k-mer strategy is best for construction of an optimal de novo assembly. Additionally, there is a lack of consensus on which evaluation metrics should be used to assess the quality of de novo transcriptome assemblies. Result Six different assembly strategies were evaluated from four different assemblers. The Trinity assembly was used in its default 25 single k-mer value while Bridger, Oases, and SOAPdenovo-Trans were performed with multiple k-mer strategies. Bridger, Oases, and SOAPdenovo-Trans used a small multiple k-mer (SMK) strategy consisting of the k-mer lengths of 21, 25, 27, 29, 31, and 33. Additionally, Oases and SOAPdenovo-Trans were performed using a large multiple k-mer (LMK) strategy consisting of k-mer lengths of 25, 35, 45, 55, 65, 75, and 85. Eleven metrics were used to evaluate each assembly strategy including three genome related evaluation metrics (contig number, N50 length, Contigs >1 kb, reads) and eight transcriptome evaluation metrics (mapped back to transcripts (RMBT), number of full length transcripts, number of open reading frames, Detonate RSEM-EVAL score, and percent alignment to the southern platyfish, Amazon molly, BUSCO and CEGMA databases). The assembly strategy that performed the best, that is it was within the top three of each evaluation metric, was the Bridger assembly (10 of 11) followed by the Oases SMK assembly (8 of 11), the Oases LMK assembly (6 of 11), the Trinity assembly (4 of 11), the SOAP LMK assembly (4 of 11), and the SOAP SMK assembly (3 of 11). Conclusion This study provides an in-depth multi k-mer strategy investigation concluding that the assembler itself had a greater impact than k-mer size regardless of the strategy employed. Additionally, the comprehensive performance

  6. Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset

    PubMed Central

    Feldmann, Friederike; Rasmussen, Angela L.; Okumura, Atsushi; Peng, Xinxia; Thomas, Matthew J.; van Doremalen, Neeltje; Haddock, Elaine; Nagy, Lee; LaCasse, Rachel; Liu, Tingting; Zhu, Jiang; McLellan, Jason S.; Scott, Dana P.; Katze, Michael G.; Feldmann, Heinz; Munster, Vincent J.

    2014-01-01

    The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies. PMID:25144235

  7. The mercury resistance (mer) operon in a marine gliding flavobacterium, Tenacibaculum discolor 9A5.

    PubMed

    Allen, Rachel C; Tu, Yen-Kuei; Nevarez, Michael J; Bobbs, Alexander S; Friesen, Joseph W; Lorsch, Jon R; McCauley, John A; Voet, Judith G; Hamlett, Nancy V

    2013-01-01

    Genes conferring mercury resistance have been investigated in a variety of bacteria and archaea but not in bacteria of the phylum Bacteroidetes, despite their importance in many environments. We found, however, that a marine gliding Bacteroidetes species, Tenacibaculum discolor, was the predominant mercury-resistant bacterial taxon cultured from a salt marsh fertilized with mercury-contaminated sewage sludge. Here we report characterization of the mercuric reductase and the narrow-spectrum mercury resistance (mer) operon from one of these strains - T. discolor 9A5. This mer operon, which confers mercury resistance when cloned into Flavobacterium johnsoniae, encodes a novel mercury-responsive ArsR/SmtB family transcriptional regulator that appears to have evolved independently from other mercury-responsive regulators, a novel putative transport protein consisting of a fusion between the integral membrane Hg(II) transporter MerT and the periplasmic Hg(II)-binding protein MerP, an additional MerP protein, and a mercuric reductase that is phylogenetically distinct from other known mercuric reductases. PMID:22816663

  8. MERS-CoV papain-like protease has deISGylating and deubiquitinating activities

    PubMed Central

    Mielech, Anna M.; Kilianski, Andy; Baez-Santos, Yahira M.; Mesecar, Andrew D.; Baker, Susan C.

    2014-01-01

    Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis. PMID:24503068

  9. MERS-CoV vaccine candidates in development: The current landscape.

    PubMed

    Modjarrad, Kayvon

    2016-06-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry. PMID:27083424

  10. Dynamical transmission model of MERS-CoV in two areas

    NASA Astrophysics Data System (ADS)

    Yong, Benny; Owen, Livia

    2016-02-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a disease first reported in Saudi Arabia in 2012 and it can be transmitted from human to human. This disease has spread to several other countries, most confirmed cases have displayed symptoms of severe acute respiratory illness and many of these patients have died. This research is aimed to construct a mathematical model for the transmission of MERS-CoV in two areas by separating the human population into two groups; susceptible and infectious groups. The dynamics of the disease is studied by a compartmental model involving ordinary differrential equations. The basic reproductive number of this disease is discussed to control the outbreak of this disease. Sensitivity analysis of this model is performed to determine the relative importance of the model parameters to the MERS-CoV transmission.

  11. Design and Performance of the MER (Mars Exploration Rovers) Solar Arrays

    NASA Technical Reports Server (NTRS)

    Stella, Paul M.; Ewell, Richard C.; Hoskin, Julie J.

    2005-01-01

    The Mars Exploration Rovers (MER) program posed a significant engineering and technology challenge. Now that the Rovers have operated beyond their original design life of three months by nearly a factor of four it is clear that the challenge was met and far exceeded. A key to the success of MER has been the enhanced power provided by the cruise and Rover solar arrays. Benefiting from a nearly 50% improvement in cell efficiency compared to the single junction GaAs cells used on Pathfinder, the MER designs were subject to many constraints both in design and in operation. These constraints included limited available panel area, changing illumination levels and temperatures, and variable shadowing, atmospheric conditions and dust accumulation for the rovers. This paper will discuss those constraints and their impact on the design. In addition, flight data will be provided to assess the performance achieved during the mission.

  12. Preventing healthcare-associated transmission of the Middle East Respiratory Syndrome (MERS): Our Achilles heel.

    PubMed

    Balkhy, Hanan H; Perl, Trish M; Arabi, Yaseen M

    2016-01-01

    Middle East Respiratory Syndrome (MERS) coronavirus is the most recent among the Coronaviridae family to jump species and infect humans. Major healthcare associated MERS outbreaks have occurred in the Middle East and Korea that affected both patients and healthcare workers. These outbreaks were characterized by intra and inter-hospital spread and were exacerbated specifically by overcrowding, delayed diagnosis and appropriate use of personal protective equipment. Recent experience with this virus emphasizes the importance of compliance with infection control practices and with other interventions addressing patient triage, placement and flow within and between healthcare facilities. Our Achilles heel remains compliance with the best infection prevention practices and their harmonization with patient flow. Both infection prevention compliance and maintenance of patient flow are critical in preventing healthcare-associated transmission of many of these emerging infectious diseases, including MERS. PMID:27158023

  13. Simrank: Rapid and sensitive general-purpose k-mer search tool

    SciTech Connect

    DeSantis, T.Z.; Keller, K.; Karaoz, U.; Alekseyenko, A.V; Singh, N.N.S.; Brodie, E.L; Pei, Z.; Andersen, G.L; Larsen, N.

    2011-04-01

    Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project (http://nihroadmap.nih.gov/hmp). Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available. Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset. Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.

  14. Compact representation of k-mer de Bruijn graphs for genome read assembly

    PubMed Central

    2013-01-01

    Background Processing of reads from high throughput sequencing is often done in terms of edges in the de Bruijn graph representing all k-mers from the reads. The memory requirements for storing all k-mers in a lookup table can be demanding, even after removal of read errors, but can be alleviated by using a memory efficient data structure. Results The FM-index, which is based on the Burrows–Wheeler transform, provides an efficient data structure providing a searchable index of all substrings from a set of strings, and is used to compactly represent full genomes for use in mapping reads to a genome: the memory required to store this is in the same order of magnitude as the strings themselves. However, reads from high throughput sequences mostly have high coverage and so contain the same substrings multiple times from different reads. I here present a modification of the FM-index, which I call the kFM-index, for indexing the set of k-mers from the reads. For DNA sequences, this requires 5 bit of information for each vertex of the corresponding de Bruijn subgraph, i.e. for each different k−1-mer, plus some additional overhead, typically 0.5 to 1 bit per vertex, for storing the equivalent of the FM-index for walking the underlying de Bruijn graph and reproducing the actual k-mers efficiently. Conclusions The kFM-index could replace more memory demanding data structures for storing the de Bruijn k-mer graph representation of sequence reads. A Java implementation with additional technical documentation is provided which demonstrates the applicability of the data structure (http://folk.uio.no/einarro/Projects/KFM-index/). PMID:24152242

  15. Value, market preferences and trade of Beche-de-mer from Pacific Island sea cucumbers.

    PubMed

    Purcell, Steven W

    2014-01-01

    Market preferences of natural resources contribute to shape their exploitation and production. Beche-de-mer, the product after gutting, cooking, salting and drying sea cucumbers, is exported worldwide to Asian dried seafood markets. A better understanding of the trade, value and market preferences of Pacific island beche-de-mer could identify critical postharvest processing techniques and management strategies for fisheries and aquaculture. Data were collected on export prices and trade of beche-de-mer from Kiribati, Fiji, Tonga and New Caledonia, and the selling prices, respective sizes and organoleptic properties of the products in stores in China. Export prices varied considerably within and among the four countries and low-value species were the most exported by volume. Most of the beche-de-mer from the four Pacific islands is exported to Hong Kong, where quality products are sold and others are distributed to mainland China. Prices of the beche-de-mer in Chinese stores varied up to ten-fold and were mostly influenced by species, body size and, to a lesser extent, physical damage to the products. Market prices across species (averaging US$15-385 kg-1) appear to have mostly increased six- to twelve-fold over the past decade. The data allude that fisheries for Holothuria scabra, H. lessoni, H. fuscogilva, H. whitmaei and Thelenota ananas should be most carefully managed because they were the highest-value species and under greatest demand. The relationships between size of beche-de-mer and sale price were species specific and highly varied. This study also highlights the need for better regulations and/or enforcement of minimum size limits in sea cucumber fisheries, which can help to maximise economic benefits of wild stocks. PMID:24736374

  16. Value, Market Preferences and Trade of Beche-De-Mer from Pacific Island Sea Cucumbers

    PubMed Central

    Purcell, Steven W.

    2014-01-01

    Market preferences of natural resources contribute to shape their exploitation and production. Beche-de-mer, the product after gutting, cooking, salting and drying sea cucumbers, is exported worldwide to Asian dried seafood markets. A better understanding of the trade, value and market preferences of Pacific island beche-de-mer could identify critical postharvest processing techniques and management strategies for fisheries and aquaculture. Data were collected on export prices and trade of beche-de-mer from Kiribati, Fiji, Tonga and New Caledonia, and the selling prices, respective sizes and organoleptic properties of the products in stores in China. Export prices varied considerably within and among the four countries and low-value species were the most exported by volume. Most of the beche-de-mer from the four Pacific islands is exported to Hong Kong, where quality products are sold and others are distributed to mainland China. Prices of the beche-de-mer in Chinese stores varied up to ten-fold and were mostly influenced by species, body size and, to a lesser extent, physical damage to the products. Market prices across species (averaging US$15–385 kg−1) appear to have mostly increased six- to twelve-fold over the past decade. The data allude that fisheries for Holothuria scabra, H. lessoni, H. fuscogilva, H. whitmaei and Thelenota ananas should be most carefully managed because they were the highest-value species and under greatest demand. The relationships between size of beche-de-mer and sale price were species specific and highly varied. This study also highlights the need for better regulations and/or enforcement of minimum size limits in sea cucumber fisheries, which can help to maximise economic benefits of wild stocks. PMID:24736374

  17. External Quality Assessment of MERS-CoV Molecular Diagnostics During the 2015 Korean Outbreak

    PubMed Central

    Seong, Moon-Woo; Lee, Seung Jun; Cho, Sung Im; Ko, Kyungphil; Kim, Mi-Na; Sung, Heungsub; Kim, Jae-Seok; Ahn, Ji Soo; Yu, Byung Su; Kim, Taek Soo; Kim, Eui Chong

    2016-01-01

    Background The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside Middle East Asia in 2015 has necessitated the rapid expansion of laboratories that conduct MERS-CoV molecular testing in Korea, together with external quality assessment (EQA) to evaluate the assays used. Methods The EQA program consisted of two phases; self-validation and blind assessment. For the first EQA phase, in vitro transcribed upstream region of the envelope gene (upE) and the open reading frame (ORF)1a RNAs were used at a concentration of 1,000 copies/µL. The test panel for the second EQA phase consisted of RNA extracts from three samples, which were obtained from two MERS-CoV positive patients and one MERS-CoV negative patient. Results The first EQA phase results for 46 participants showed a linear relationship between the threshold cycle (CT) values of RNA materials and the logarithmic concentrations for both upE and ORF1a gene targets (R2=0.73 and 0.75, respectively). The mean CT value for each concentration was different depending on which commercial kit was used for the assay. Among the three commonly used kits, PowerChek MERS Real-Time PCR kit (KogeneBiotech, Korea) showed the lowest CT values at all concentrations of upE and most concentrations of ORF1a. The second EQA phase results for 47 participants were 100% correct for all tested samples. Conclusions This EQA survey demonstrates that the MERS-CoV molecular testing performed in Korea during the 2015 outbreak is of robust capability. However, careful establishment and validation of a cut-off value are recommended to ensure good analytical sensitivity. PMID:26915611

  18. Healthcare Workers Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak

    PubMed Central

    Khalid, Imran; Khalid, Tabindeh J.; Qabajah, Mohammed R.; Barnard, Aletta G.; Qushmaq, Ismael A.

    2016-01-01

    Objective Healthcare workers (HCWs) are at high risk of contracting Middle East respiratory syndrome coronavirus (MERS-CoV) during an epidemic. We explored the emotions, perceived stressors, and coping strategies of healthcare workers who worked during a MERS-CoV outbreak in our hospital. Design A cross-sectional descriptive survey design. Setting A tertiary care hospital. Participants HCWs (150) who worked in high risk areas during the April–May 2014 MERS-CoV outbreak that occurred in Jeddah, Saudi Arabia. Methods We developed and administered a “MERS-CoV staff questionnaire” to study participants. The questionnaire consisted of 5 sections with 72 questions. The sections evaluated hospital staffs emotions, perceived stressors, factors that reduced their stress, coping strategies, and motivators to work during future outbreaks. Responses were scored on a scale from 0–3. The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. Results Completed questionnaires were returned by 117 (78%) of the participants. The results had many unique elements. HCWs ethical obligation to their profession pushed them to continue with their jobs. The main sentiments centered upon fear of personal safety and well-being of colleagues and family. Positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among HCWs after adopting strict protective measures alleviated their fear and drove them through the epidemic. They appreciated recognition of their efforts by hospital management and expected similar acknowledgment, infection control guidance, and equipment would entice them to work during future epidemics. Conclusion The MERS-CoV outbreak was a distressing time for our staff. Hospitals can enhance HCWs experiences during any future MERS-CoV outbreak by focusing on the above mentioned aspects. PMID:26847480

  19. Local Surface Reconstruction from MER images using Stereo Workstation

    NASA Astrophysics Data System (ADS)

    Shin, Dongjoe; Muller, Jan-Peter

    2010-05-01

    The authors present a semi-automatic workflow that reconstructs the 3D shape of the martian surface from local stereo images delivered by PnCam or NavCam on systems such as the NASA Mars Exploration Rover (MER) Mission and in the future the ESA-NASA ExoMars rover PanCam. The process is initiated with manually selected tiepoints on a stereo workstation which is then followed by a tiepoint refinement, stereo-matching using region growing and Levenberg-Marquardt Algorithm (LMA)-based bundle adjustment processing. The stereo workstation, which is being developed by UCL in collaboration with colleagues at the Jet Propulsion Laboratory (JPL) within the EU FP7 ProVisG project, includes a set of practical GUI-based tools that enable an operator to define a visually correct tiepoint via a stereo display. To achieve platform and graphic hardware independence, the stereo application has been implemented using JPL's JADIS graphic library which is written in JAVA and the remaining processing blocks used in the reconstruction workflow have also been developed as a JAVA package to increase the code re-usability, portability and compatibility. Although initial tiepoints from the stereo workstation are reasonably acceptable as true correspondences, it is often required to employ an optional validity check and/or quality enhancing process. To meet this requirement, the workflow has been designed to include a tiepoint refinement process based on the Adaptive Least Square Correlation (ALSC) matching algorithm so that the initial tiepoints can be further enhanced to sub-pixel precision or rejected if they fail to pass the ALSC matching threshold. Apart from the accuracy of reconstruction, it is obvious that the other criterion to assess the quality of reconstruction is the density (or completeness) of reconstruction, which is not attained in the refinement process. Thus, we re-implemented a stereo region growing process, which is a core matching algorithm within the UCL

  20. The MER Mossbauer Spectrometers: 40 Months of Operation on the Martian Surface

    NASA Technical Reports Server (NTRS)

    Fleischer, Iris; Rodionov, D.; Schroeder, C.; Morris, R.; Yen, A.; Ming, D.; McCoy, T.; Mittlefehldt, D.; Gellert, R.; Cohen, B.; Schmidt, M.; Klingelhoefer, Goestar

    2007-01-01

    The primary MER objectives have been successfully completed. The total integration time of all MB measurements exceeds the duration of the primary 90-sols-mission for Spirit's MB spectrometer, and approaches this value for Opportunity's MB spectrometer. Both MB spectrometers continue to accumulate valuable scientific data after three years of operation (data is available for download [13]) The identification of aqueous minerals such as goethite in Gusev crater and jarosite at Meridiani Planum by the MER Mossbauer spectrometers is strong evidence for past water activity at the two landing sites.

  1. Interleukin 17 Regulates Mer Tyrosine Kinase–Positive Cells in Pseudomonas aeruginosa Keratitis

    PubMed Central

    Li, Cui; McClellan, Sharon A.; Barrett, Ronald; Hazlett, Linda D.

    2014-01-01

    Purpose. To determine if IL-17 regulates Mer tyrosine kinase–positive (MerTK+) cells in Pseudomonas aeruginosa keratitis. Methods. Interleukin 17 was tested in normal and infected cornea of susceptible C57BL/6 and resistant BALB/c mice. The latter were treated with recombinant mouse (rm) IL-17; both groups were treated with IL-17 neutralizing antibody. Mice were infected, and clinical score, PCR, ELISA, and myeloperoxidase (MPO) assays tested expression of proinflammatory and anti-inflammatory mediators and polymorphonuclear neutrophilic leukocyte (PMN) infiltrate. Fas and Fas ligand (FasL) protein levels were assessed in both mouse strains, while MerTK+ cells were examined by immunostaining and cell sorting before and after IL-17 neutralization. Results. The IL-17 mRNA and protein were higher in C57BL/6 versus BALB/c cornea after infection. The rmIL-17 treatment of BALB/c mice modified proinflammatory and anti-inflammatory mediators, but clinical score and MPO assay revealed no differences. However, only BALB/c mice treated with IL-17 neutralizing antibody showed increased disease, macrophage inflammatory protein (MIP) 2, and MPO levels. Fas and FasL protein levels, elevated earlier in BALB/c versus C57BL/6 mice, correlated with significantly more MerTK+ cells in BALB/c cornea at 3 days after infection. Neutralization of IL-17 in C57BL/6 mice elevated MerTK+ cells, while similar treatment of BALB/c mice significantly decreased them. Conclusions. These data provide evidence that IL-17 expression is higher in C57BL/6 versus BALB/c cornea after infection and that the latter group has more MerTK+ cells. Exogenous rmIL-17 failed to shift the disease response in resistant mice, but its neutralization resulted in worsened disease and reduced MerTK+ cells. Neutralization of IL-17 in C57BL/6 mice increased MerTK+ cells but did not dramatically shift the disease response. PMID:25298414

  2. 77 FR 49059 - Requested Administrative Waiver of the Coastwise Trade Laws: Vessel CHAT DE MER; Invitation for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... published on April 11, 2000 (65 FR 19477-78). By Order of the Maritime Administrator. Dated: August 9, 2012... Maritime Administration Requested Administrative Waiver of the Coastwise Trade Laws: Vessel CHAT DE MER... of the vessel CHAT DE MER is: Intended Commercial Use of Vessel: Primarily carrying passengers...

  3. Crystal Structures of the Organomercurial Lyase MerB in Its Free and Mercury-Bound Forms

    SciTech Connect

    Lafrance-Vanasse, J.; Lefebvre, M; Di Lello, P; Sygusch, J; Omichinski, J

    2009-01-01

    Bacteria resistant to methylmercury utilize two enzymes (MerA and MerB) to degrade methylmercury to the less toxic elemental mercury. The crucial step is the cleavage of the carbon-mercury bond of methylmercury by the organomercurial lyase (MerB). In this study, we determined high resolution crystal structures of MerB in both the free (1.76-{angstrom} resolution) and mercury-bound (1.64-{angstrom} resolution) states. The crystal structure of free MerB is very similar to theNMRstructure, but important differences are observed when comparing the two structures. In the crystal structure, an amino-terminal-helix that is not present in the NMR structure makes contact with the core region adjacent to the catalytic site. This interaction between the amino-terminal helix and the core serves to bury the active site of MerB. The crystal structures also provide detailed insights into the mechanism of carbon-mercury bond cleavage by MerB. The structures demonstrate that two conserved cysteines (Cys-96 and Cys-159) play a role in substrate binding, carbon-mercury bond cleavage, and controlled product (ionic mercury) release. In addition, the structures establish that an aspartic acid (Asp-99) in the active site plays a crucial role in the proton transfer step required for the cleavage of the carbon-mercury bond. These findings are an important step in understanding the mechanism of carbon-mercury bond cleavage by MerB.

  4. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia.

    PubMed

    Sabir, Jamal S M; Lam, Tommy T-Y; Ahmed, Mohamed M M; Li, Lifeng; Shen, Yongyi; Abo-Aba, Salah E M; Qureshi, Muhammd I; Abu-Zeid, Mohamed; Zhang, Yu; Khiyami, Mohammad A; Alharbi, Njud S; Hajrah, Nahid H; Sabir, Meshaal J; Mutwakil, Mohammed H Z; Kabli, Saleh A; Alsulaimany, Faten A S; Obaid, Abdullah Y; Zhou, Boping; Smith, David K; Holmes, Edward C; Zhu, Huachen; Guan, Yi

    2016-01-01

    Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus. PMID:26678874

  5. merA gene expression in aquatic environments measured by mRNA production and Hg(II) volatilization.

    PubMed Central

    Nazaret, S; Jeffrey, W H; Saouter, E; Von Haven, R; Barkay, T

    1994-01-01

    The relationship of merA gene expression (specifying the enzyme mercuric reductase) to mercury volatilization in aquatic microbial communities was investigated with samples collected at a mercury-contaminated freshwater pond, Reality Lake, in Oak Ridge, Tenn. Levels of merA mRNA transcripts and the rate of inorganic mercury [Hg(II)] volatilization were related to the concentration of mercury in the water and to heterotrophic activity in field samples and laboratory incubations of pond water in which microbial heterotrophic activity and Hg(II) concentration were manipulated. Levels of merA-specific mRNA and Hg(II) volatilization were influenced more by microbial metabolic activity than by the concentration of mercury. merA-specific transcripts were detected in some samples which did not reduce Hg(II), suggesting that rates of mercury volatilization in environmental samples may not always be proportional to merA expression. PMID:7527625

  6. Structure and Conformational Dynamics of the Metalloregulator MerR upon Binding of Hg(II)

    SciTech Connect

    Guo, Hao-Bo; Johs, Alexander; Parks, Jerry M; Olliff, Lyn; Miller, Susan M; Summers, Anne O; Liang, Liyuan; Smith, Jeremy C

    2010-03-01

    The bacterial metalloregulator MerR is the index case of an eponymous family of regulatory proteins, which controls the transcription of a set of genes (the mer operon) conferring mercury resistance in many bacteria. Homodimeric MerR represses transcription in the absence of mercury and activates transcription upon Hg(II) binding. Here, the average structures of the apo and Hg(II)-bound forms of MerR in aqueous solution are examined using small-angle X-ray scattering, indicating an extended conformation of the metal-bound protein and revealing the existence of a novel compact conformation in the absence of Hg(II). Molecular dynamics (MD) simulations are performed to characterize the conformational dynamics of the Hg(II)-bound form. In both small-angle X-ray scattering and MD, the average torsional angle between DNA-binding domains is approximately 65 degrees. Furthermore, in MD, interdomain motions on a timescale of approximately 10 ns involving large-amplitude (approximately 20 A) domain opening-and-closing, coupled to approximately 40 degrees variations of interdomain torsional angle, are revealed. This correlated domain motion may propagate allosteric changes from the metal-binding site to the DNA-binding site while maintaining DNA contacts required to initiate DNA underwinding.

  7. Structure and Conformational Dynamics of the Metalloregulator MerR upon Binding of Hg(II)

    SciTech Connect

    Guo, Hao-Bo; Johs, Alexander; Parks, Jerry M; Olliff, Lyn; Miller, Susan M; Summers, Anne O; Liang, Liyuan; Smith, Jeremy C

    2010-05-01

    The bacterial metalloregulator MerR is the index case of an eponymous family of regulatory proteins, which controls the transcription of a set of genes (the mer operon) conferring mercury resistance in many bacteria. Homodimeric MerR represses transcription in the absence of mercury and activates transcription upon Hg(II) binding. Here, the average structures of the apo and Hg(II)-bound forms of MerR in aqueous solution are examined using small-angle X-ray scattering, indicating an extended conformation of the metal-bound protein and revealing the existence of a novel compact conformation in the absence of Hg(II). Molecular dynamics (MD) simulations are performed to characterize the conformational dynamics of the Hg(II)-bound form. In both small-angle X-ray scattering and MD, the average torsional angle between DNA-binding domains is not, vert, similar 65 . Furthermore, in MD, interdomain motions on a timescale of not, vert, similar 10 ns involving large-amplitude (not, vert, similar 20 ) domain opening-and-closing, coupled to not, vert, similar 40 variations of interdomain torsional angle, are revealed. This correlated domain motion may propagate allosteric changes from the metal-binding site to the DNA-binding site while maintaining DNA contacts required to initiate DNA underwinding.

  8. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia

    PubMed Central

    Hajeer, Ali H.; Luke, Thomas; Raviprakash, Kanakatte; Balkhy, Hanan; Johani, Sameera; Al-Dawood, Abdulaziz; Al-Qahtani, Saad; Al-Omari, Awad; Al-Hameed, Fahad; Hayden, Frederick G.; Fowler, Robert; Bouchama, Abderrezak; Shindo, Nahoko; Al-Khairy, Khalid; Carson, Gail; Taha, Yusri; Sadat, Musharaf; Alahmadi, Mashail

    2016-01-01

    We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness. PMID:27532807

  9. Enhanced MERS coronavirus surveillance of travelers from the Middle East to England.

    PubMed

    Thomas, Helen Lucy; Zhao, Hongxin; Green, Helen K; Boddington, Nicola L; Carvalho, Carlos F A; Osman, Husam K; Sadler, Carol; Zambon, Maria; Bermingham, Alison; Pebody, Richard G

    2014-09-01

    During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative. PMID:25148267

  10. Enhanced MERS Coronavirus Surveillance of Travelers from the Middle East to England

    PubMed Central

    Thomas, Helen Lucy; Zhao, Hongxin; Green, Helen K.; Boddington, Nicola L.; Carvalho, Carlos F.A.; Osman, Husam K.; Sadler, Carol; Zambon, Maria; Bermingham, Alison

    2014-01-01

    During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative. PMID:25148267

  11. Phase coexistence and spatial correlations in reconstituting k-mer models.

    PubMed

    Chatterjee, Amit Kumar; Daga, Bijoy; Mohanty, P K

    2016-07-01

    In reconstituting k-mer models, extended objects that occupy several sites on a one-dimensional lattice undergo directed or undirected diffusion, and reconstitute-when in contact-by transferring a single monomer unit from one k-mer to the other; the rates depend on the size of participating k-mers. This polydispersed system has two conserved quantities, the number of k-mers and the packing fraction. We provide a matrix product method to write the steady state of this model and to calculate the spatial correlation functions analytically. We show that for a constant reconstitution rate, the spatial correlation exhibits damped oscillations in some density regions separated, from other regions with exponential decay, by a disorder surface. In a specific limit, this constant-rate reconstitution model is equivalent to a single dimer model and exhibits a phase coexistence similar to the one observed earlier in totally asymmetric simple exclusion process on a ring with a defect. PMID:27575091

  12. Geology of a Proposed MER Landing Site in Western Melas Chasma

    NASA Technical Reports Server (NTRS)

    Weitz, C. M.; Parker, T. J.; Anderson, F. S.; Grant, J. A.

    2002-01-01

    A proposed landing site for the Mars Exploration Rover (MER) has been identified in western Melas Chasma. The landing ellipse contains a blocky, bright deposit which we propose formed as a landslide, perhaps beneath a former lake. Additional information is contained in the original extended abstract.

  13. Clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination.

    PubMed

    Takanashi, Jun-Ichi; Shiihara, Takashi; Hasegawa, Takeshi; Takayanagi, Masaru; Hara, Munetsugu; Okumura, Akihisa; Mizuguchi, Masashi

    2015-02-15

    We retrospectively collected three patients with clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination, and reviewed five patients, including two patients previously reported. The five patients (all males, aged 1 to 9) presented with fever, vomiting, or headache as the initial symptoms (day 0), suggesting meningitis, at 13 to 21 days after mumps vaccination. Consciousness disturbance, delirious behavior, seizures, or dysarthria was observed on days 1 to 3, which had completely resolved before day 11. Hyponatremia was observed in all patients. A cerebrospinal fluid study showed pleocytosis, and confirmed the vaccine strain genome. MRI revealed reduced diffusion in the splenium of the corpus callosum on days 2 to 4, which had completely disappeared on the follow-up studies performed on days 7-15. EEG showed high voltage slow wave in three patients, which later normalized. These findings led to a diagnosis of MERS after mumps vaccination. MERS after mumps vaccination may be more common than previously considered. MERS is suspected when a male patient after mumps vaccination presents with neurological symptoms with hyponatremia, following symptoms of aseptic meningitis, and MRI would be performed to examine the splenium of the corpus callosum. PMID:25542078

  14. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

    PubMed

    Arabi, Yaseen M; Hajeer, Ali H; Luke, Thomas; Raviprakash, Kanakatte; Balkhy, Hanan; Johani, Sameera; Al-Dawood, Abdulaziz; Al-Qahtani, Saad; Al-Omari, Awad; Al-Hameed, Fahad; Hayden, Frederick G; Fowler, Robert; Bouchama, Abderrezak; Shindo, Nahoko; Al-Khairy, Khalid; Carson, Gail; Taha, Yusri; Sadat, Musharaf; Alahmadi, Mashail

    2016-09-01

    We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness. PMID:27532807

  15. MER Surface Phase; Blurring the Line Between Fault Protection and What is Supposed to Happen

    NASA Technical Reports Server (NTRS)

    Reeves, Glenn E.

    2008-01-01

    An assessment on the limitations of communication with MER rovers and how such constraints drove the system design, flight software and fault protection architecture, blurring the line between traditional fault protection and expected nominal behavior, and requiring the most novel autonomous and semi-autonomous elements of the vehicle software including communication, surface mobility, attitude knowledge acquisition, fault protection, and the activity arbitration service.

  16. Multi-Agent Modeling and Simulation Approach for Design and Analysis of MER Mission Operations

    NASA Technical Reports Server (NTRS)

    Seah, Chin; Sierhuis, Maarten; Clancey, William J.

    2005-01-01

    A space mission operations system is a complex network of human organizations, information and deep-space network systems and spacecraft hardware. As in other organizations, one of the problems in mission operations is managing the relationship of the mission information systems related to how people actually work (practices). Brahms, a multi-agent modeling and simulation tool, was used to model and simulate NASA's Mars Exploration Rover (MER) mission work practice. The objective was to investigate the value of work practice modeling for mission operations design. From spring 2002 until winter 2003, a Brahms modeler participated in mission systems design sessions and operations testing for the MER mission held at Jet Propulsion Laboratory (JPL). He observed how designers interacted with the Brahms tool. This paper discussed mission system designers' reactions to the simulation output during model validation and the presentation of generated work procedures. This project spurred JPL's interest in the Brahms model, but it was never included as part of the formal mission design process. We discuss why this occurred. Subsequently, we used the MER model to develop a future mission operations concept. Team members were reluctant to use the MER model, even though it appeared to be highly relevant to their effort. We describe some of the tool issues we encountered.

  17. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon

    PubMed Central

    Kane, Aunica L.; Al-Shayeb, Basem; Holec, Patrick V.; Rajan, Srijay; Le Mieux, Nicholas E.; Heinsch, Stephen C.; Psarska, Sona; Aukema, Kelly G.; Sarkar, Casim A.; Nater, Edward A.; Gralnick, Jeffrey A.

    2016-01-01

    Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB) from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0). E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation. PMID:26761437

  18. Metalloregulatory DNA-Binding Protein Encoded by the merR Gene: Isolation and Characterization

    NASA Astrophysics Data System (ADS)

    O'Halloran, Thomas; Walsh, Christopher

    1987-01-01

    The MerR protein mediates the induction of the mercury resistance phenotype in bacteria; it has been isolated in order to study the effects of metal-ion induced changes in the metabolism of prokaryotic cells at the molecular level. After DNA sequences responsible for negative autoregulation were removed, the 16-kilodalton protein was overproduced and purified to more than 90 percent homogeneity by a salt extraction procedure that yields about 5 milligrams of protein per gram of cells. Complementation data, amino terminal analysis, gel filtration, and deoxyribonuclease I protection studies demonstrate that the purified merR gene product is a dimer under nondenaturing conditions and that it binds specifically to DNA, in the presence and absence of mercury, at a palindromic site which is directly between the -10 and -35 regions of the structural genes and adjacent to its own promoter. These initial results indicate that MerR is a DNA-binding metalloregulatory protein that plays a central role in this heavy metal responsive system and they delineate an operator site in the mer operon.

  19. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon.

    PubMed

    Kane, Aunica L; Al-Shayeb, Basem; Holec, Patrick V; Rajan, Srijay; Le Mieux, Nicholas E; Heinsch, Stephen C; Psarska, Sona; Aukema, Kelly G; Sarkar, Casim A; Nater, Edward A; Gralnick, Jeffrey A

    2016-01-01

    Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB) from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0). E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation. PMID:26761437

  20. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Acrylonitrile/styrene copoly-mer. 177.1040 Section 177.1040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use...

  1. Direct Measurement of Hg(II) Removal from Organomercurial Lyase (MerB) by Tryptophan Fluorescence: NmerA Domain of Co-evolved γ -Proteobacterial Mercuric Ion Reductase (MerA) Is More Efficient than MerA Catalytic Core or Glutathione†

    PubMed Central

    Hong, Baoyu; Nauss, Rachel; Harwood, Ian; Miller, Susan M.

    2011-01-01

    Aerobic and facultative bacteria and archaea harboring mer loci exhibit resistance to the toxic effects of Hg(II) and organomercurials [RHg(I)]. In broad spectrum resistance, RHg(I) is converted to less toxic Hg(0) in the cytosol by the sequential action of organomercurial lyase (MerB: RHg(I) --> RH + Hg(II)) and mercuric ion reductase (MerA: Hg(II) --> Hg(0)) enzymes, requiring transfer of Hg(II) from MerB to MerA. Although previous studies with γ-proteobacterial versions of MerA and a non-physiological Hg(II)-DTT-MerB complex qualitatively support a pathway for direct transfer between proteins, assessment of the relative efficiencies of Hg(II) transfer to the two different di-cysteine motifs in γ-proteobacterial MerA and to competing cellular thiol is lacking. Here we show the intrinsic tryptophan fluorescence of γ-proteobacterial MerB is sensitive to Hg(II) binding and use this to probe the kinetics of Hg(II) removal from MerB by the N-terminal domain (NmerA) and catalytic core C-terminal cysteine pairs of its co-evolved MerA, and by glutathione (GSH), the major competing cellular thiol in γ-proteobacteria. At physiologically relevant concentrations, reaction with a 10-fold excess NmerA over HgMerB removes ≥ 92% Hg(II), while similar extents of reaction require more than 1000-fold excess of GSH. Kinetically, the apparent second order rate constant for Hg(II) transfer from MerB to NmerA, at 2.3 ± 0.1 × 104 M−1 s−1 is ~ 100-fold greater than that for GSH (1.2 ± 0.2 × 102 M−1 s−1) or the MerA catalytic core (1.2 × 102 M−1 s−1), establishing transfer to the metallochaperone-like NmerA domain as the kinetically favored pathway in this co-evolved system. PMID:20722420

  2. Direct measurement of mercury(II) removal from organomercurial lyase (MerB) by tryptophan fluorescence: NmerA domain of coevolved γ-proteobacterial mercuric ion reductase (MerA) is more efficient than MerA catalytic core or glutathione .

    PubMed

    Hong, Baoyu; Nauss, Rachel; Harwood, Ian M; Miller, Susan M

    2010-09-21

    Aerobic and facultative bacteria and archaea harboring mer loci exhibit resistance to the toxic effects of Hg(II) and organomercurials [RHg(I)]. In broad spectrum resistance, RHg(I) is converted to less toxic Hg(0) in the cytosol by the sequential action of organomercurial lyase (MerB: RHg(I) → RH + Hg(II)) and mercuric ion reductase (MerA: Hg(II) → Hg(0)) enzymes, requiring transfer of Hg(II) from MerB to MerA. Although previous studies with γ-proteobacterial versions of MerA and a nonphysiological Hg(II)-DTT-MerB complex qualitatively support a pathway for direct transfer between proteins, assessment of the relative efficiencies of Hg(II) transfer to the two different dicysteine motifs in γ-proteobacterial MerA and to competing cellular thiol is lacking. Here we show the intrinsic tryptophan fluorescence of γ-proteobacterial MerB is sensitive to Hg(II) binding and use this to probe the kinetics of Hg(II) removal from MerB by the N-terminal domain (NmerA) and catalytic core C-terminal cysteine pairs of its coevolved MerA and by glutathione (GSH), the major competing cellular thiol in γ-proteobacteria. At physiologically relevant concentrations, reaction with a 10-fold excess of NmerA over HgMerB removes ≥92% Hg(II), while similar extents of reaction require more than 1000-fold excess of GSH. Kinetically, the apparent second-order rate constant for Hg(II) transfer from MerB to NmerA, at (2.3 ± 0.1) × 10(4) M(-1) s(-1), is ∼100-fold greater than that for GSH ((1.2 ± 0.2) × 10(2) M(-1) s(-1)) or the MerA catalytic core (1.2 × 10(2) M(-1) s(-1)), establishing transfer to the metallochaperone-like NmerA domain as the kinetically favored pathway in this coevolved system. PMID:20722420

  3. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo.

    PubMed

    Luke, Thomas; Wu, Hua; Zhao, Jincun; Channappanavar, Rudragouda; Coleman, Christopher M; Jiao, Jin-An; Matsushita, Hiroaki; Liu, Ye; Postnikova, Elena N; Ork, Britini L; Glenn, Gregory; Flyer, David; Defang, Gabriel; Raviprakash, Kanakatte; Kochel, Tadeusz; Wang, Jonathan; Nie, Wensheng; Smith, Gale; Hensley, Lisa E; Olinger, Gene G; Kuhn, Jens H; Holbrook, Michael R; Johnson, Reed F; Perlman, Stanley; Sullivan, Eddie; Frieman, Matthew B

    2016-02-17

    As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A γ-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody-dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERS-CoV infection and/or other emerging infectious diseases. PMID:26888429

  4. Construction and characterization of a mercury-independent MerR activator (MerRAC): transcriptional activation in the absence of Hg(II) is accompanied by DNA distortion.

    PubMed Central

    Parkhill, J; Ansari, A Z; Wright, J G; Brown, N L; O'Halloran, T V

    1993-01-01

    The MeR regulatory protein of transposon Tn501 controls the expression of the mercury resistance (mer) genes in response to the concentration of mercuric ions. MerR is unique among prokaryotic regulatory proteins so far described in that it acts as a repressor [-Hg(II)] and an activator [+Hg(II)] of transcription of the mer genes, but binds to a single site on the DNA in both cases. This transcriptional activation process has been postulated to involve a protein-induced conformational change in the DNA that allows RNA polymerase more readily to form an open complex at the promoter. It has been shown [Frantz and O'Halloran (1990) Biochemistry, 29, 4747-4751] that activation of transcription by MerR in the presence of mercury is accompanied by hypersensitivity of the operator to chemical nucleases that are sensitive to local distortion in DNA structure. Here we describe specific mutations in MerR that allow the protein to stimulate transcription in the absence of the allosteric activator Hg(II). We demonstrate that the degree of activation caused by these mutants directly correlates with the degree of DNA distortion as measured by the hypersensitivity of MerR-DNA complexes to the nuclease Cu-5-phenyl-o-phenanthroline. These results support the model described above. Images PMID:8440234

  5. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines

    PubMed Central

    Ma, Cuiqing; Li, Ye; Wang, Lili; Zhao, Guangyu; Tao, Xinrong; Tseng, Chien-Te K; Zhou, Yusen; Du, Lanying; Jiang, Shibo

    2014-01-01

    Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV. PMID:24560617

  6. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012.

    PubMed

    Johnson, Reed F; Bagci, Ulas; Keith, Lauren; Tang, Xianchun; Mollura, Daniel J; Zeitlin, Larry; Qin, Jing; Huzella, Louis; Bartos, Christopher J; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H; Paulty, Michael H; Velasco, Jesus; Whaley, Kevin J; Johnson, Joshua C; Pettitt, James; Ork, Britini L; Solomon, Jeffrey; Oberlander, Nicholas; Zhu, Quan; Sun, Jiusong; Holbrook, Michael R; Olinger, Gene G; Baric, Ralph S; Hensley, Lisa E; Jahrling, Peter B; Marasco, Wayne A

    2016-03-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. PMID:26828465

  7. Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors.

    PubMed

    Wang, Sheng-Biao; Cui, Mu-Tian; Wang, Xiao-Feng; Ohkoshi, Emika; Goto, Masuo; Yang, De-Xuan; Li, Linna; Yuan, Shoujun; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Xie, Lan

    2016-07-01

    Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68μM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54μM), as well as other human tumor cell lines (GI50<20μM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6μg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound. PMID:27238842

  8. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia.

    PubMed

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; Deryckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  9. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    PubMed Central

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; DeRyckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  10. Protective Effect of Intranasal Regimens Containing Peptidic Middle East Respiratory Syndrome Coronavirus Fusion Inhibitor Against MERS-CoV Infection.

    PubMed

    Channappanavar, Rudragouda; Lu, Lu; Xia, Shuai; Du, Lanying; Meyerholz, David K; Perlman, Stanley; Jiang, Shibo

    2015-12-15

    To gain entry into the target cell, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) uses its spike (S) protein S2 subunit to fuse with the plasma or endosomal membrane. Previous work identified a peptide derived from the heptad repeat (HR) 2 domain in S2 subunit, HR2P, which potently blocked MERS-CoV S protein-mediated membrane fusion. Here, we tested an HR2P analogue with improved pharmaceutical property, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo. HR2P-M2 was highly effective in inhibiting MERS-CoV S protein-mediated cell-cell fusion and infection by pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region. It interacted with the HR1 peptide to form stable α-helical complex and blocked six-helix bundle formation between the HR1 and HR2 domains in the viral S protein. Intranasally administered HR2P-M2 effectively protected adenovirus serotype-5-human dipeptidyl peptidase 4-transduced mice from infection by MERS-CoV strains with or without mutations in the HR1 region of S protein, with >1000-fold reduction of viral titers in lung, and the protection was enhanced by combining HR2P-M2 with interferon β. These results indicate that this combination regimen merits further development to prevent MERS in high-risk populations, including healthcare workers and patient family members, and to treat MERS-CoV-infected patients. PMID:26164863

  11. UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo

    PubMed Central

    Christoph, Sandra; DeRyckere, Deborah; Schlegel, Jennifer; Frazer, J. Kimble; Batchelor, Lance A.; Trakhimets, Alesia Y.; Sather, Susan; Hunter, Debra M.; Cummings, Christopher; Liu, Jing; Yang, Chao; Kireev, Dmitri; Simpson, Catherine; Norris-Drouin, Jacqueline; Hull-Ryde, Emily A.; Janzen, William P.; Johnson, Gary L.; Wang, Xiaodong; Frye, Stephen V.; Earp, H. Shelton; Graham, Douglas K.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biological subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces pro-survival signaling, increases chemosensitivity, and delays development of leukaemia in vivo suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiation have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (ATRT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small molecule Mer inhibitor. This manuscript describes the biochemical and biological effects of UNC569 in ALL and ATRT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 µM for 2 weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced green fluorescent protein. UNC569 induced >50% reduction in tumor burden compared to vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and ATRT. PMID:23997116

  12. NCI Researchers Discover Exceptionally Potent Antibodies with Potential for Prophylaxis and Therapy of MERS-Coronavirus Infections | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer In a recent article published in the Journal of Virology, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Laboratory of Experimental Immunology (LEI), Cancer and Inflammation Program, NCI Center for Cancer Research, reported the identification of three human monoclonal antibodies (m336, m337, and m338) that target the part of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that is responsible for binding to its receptor. These antibodies are exceptionally potent inhibitors of MERS-CoV infection and also provide a basis for creating a future MERS-CoV vaccine.

  13. The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Does Not Replicate in Syrian Hamsters

    PubMed Central

    de Wit, Emmie; Prescott, Joseph; Baseler, Laura; Bushmaker, Trenton; Thomas, Tina; Lackemeyer, Matthew G.; Martellaro, Cynthia; Milne-Price, Shauna; Haddock, Elaine; Haagmans, Bart L.; Feldmann, Heinz; Munster, Vincent J.

    2013-01-01

    In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters. PMID:23844250

  14. Application of State Analysis and Goal-Based Operations to a MER Mission Scenario

    NASA Technical Reports Server (NTRS)

    Morris, J. Richard; Ingham, Michel D.; Mishkin, Andrew H.; Rasmussen, Robert D.; Starbird, Thomas W.

    2006-01-01

    State Analysis is a model-based systems engineering methodology employing a rigorous discovery process which articulates operations concepts and operability needs as an integrated part of system design. The process produces requirements on system and software design in the form of explicit models which describe the behavior of states and the relationships among them. By applying State Analysis to an actual MER flight mission scenario, this study addresses the specific real world challenges of complex space operations and explores technologies that can be brought to bear on future missions. The paper describes the tools currently used on a daily basis for MER operations planning and provides an in-depth description of the planning process, in the context of a Martian day's worth of rover engineering activities, resource modeling, flight rules, science observations, and more. It then describes how State Analysis allows for the specification of a corresponding goal-based sequence that accomplishes the same objectives, with several important additional benefits.

  15. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir.

    PubMed

    Mohd, Hamzah A; Al-Tawfiq, Jaffar A; Memish, Ziad A

    2016-01-01

    Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections. PMID:27255185

  16. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters.

    PubMed

    de Wit, Emmie; Prescott, Joseph; Baseler, Laura; Bushmaker, Trenton; Thomas, Tina; Lackemeyer, Matthew G; Martellaro, Cynthia; Milne-Price, Shauna; Haddock, Elaine; Haagmans, Bart L; Feldmann, Heinz; Munster, Vincent J

    2013-01-01

    In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters. PMID:23844250

  17. NCI Scientists Solve Structure of Protein that Enables MERS Virus to Spread | Poster

    Cancer.gov

    Scientists at the Frederick National Lab have produced three crystal structures that reveal a specific part of a protein that can be targeted to fight the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an emerging viral respiratory illness. Senior Investigator David Waugh, Ph.D., Macromolecular Crystallography Laboratory, has solved the structure of an enzyme known as the 3C-like protease (3CLpro), which, if blocked, can prevent the virus from replicating...

  18. MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.

    PubMed

    Healy, Luke M; Perron, Gabrielle; Won, So-Yoon; Michell-Robinson, Mackenzie A; Rezk, Ayman; Ludwin, Samuel K; Moore, Craig S; Hall, Jeffery A; Bar-Or, Amit; Antel, Jack P

    2016-04-15

    Multifocal inflammatory lesions featuring destruction of lipid-rich myelin are pathologic hallmarks of multiple sclerosis. Lesion activity is assessed by the extent and composition of myelin uptake by myeloid cells present in such lesions. In the inflamed CNS, myeloid cells are comprised of brain-resident microglia, an endogenous cell population, and monocyte-derived macrophages, which infiltrate from the systemic compartment. Using microglia isolated from the adult human brain, we demonstrate that myelin phagocytosis is dependent on the polarization state of the cells. Myelin ingestion is significantly enhanced in cells exposed to TGF-β compared with resting basal conditions and markedly reduced in classically activated polarized cells. Transcriptional analysis indicated that TGF-β-treated microglia closely resembled M0 cells. The tyrosine kinase phagocytic receptor MerTK was one of the most upregulated among a select number of differentially expressed genes in TGF-β-treated microglia. In contrast, MerTK and its known ligands, growth arrest-specific 6 and Protein S, were downregulated in classically activated cells. MerTK expression and myelin phagocytosis were higher in CNS-derived microglia than observed in monocyte-derived macrophages, both basally and under all tested polarization conditions. Specific MerTK inhibitors reduced myelin phagocytosis and the resultant anti-inflammatory biased cytokine responses for both cell types. Defining and modulating the mechanisms that regulate myelin phagocytosis has the potential to impact lesion and disease evolution in multiple sclerosis. Relevant effects would include enhancing myelin clearance, increasing anti-inflammatory molecule production by myeloid cells, and thereby permitting subsequent tissue repair. PMID:26962228

  19. Mechanism of Hg-C Protonolysis in the Organomercurial Lyase MerB

    SciTech Connect

    Parks, Jerry M; Guo, Hong; Liang, Liyuan; Miller, Susan M; Summers, Anne O; Smith, Jeremy C

    2009-01-01

    Demethylation is a key reaction in global mercury cycling. The bacterial organomercurial lyase, MerB, catalyzes the demethylation of a wide range of organomercurials via Hg-C protonolysis. Two strictly conserved cysteine residues in the active site are required for catalysis, but the source of the catalytic proton and the detailed reaction mechanism have not been determined. Here, the two major proposed reaction mechanisms of MerB are investigated and compared using hybrid density functional theory calculations. A model of the active site was constructed from an X-ray crystal structure of the Hg(II)-bound MerB product complex. Stationary point structures and energies characterized for the Hg-C protonolysis of methylmercury rule out the direct protonation mechanism in which a cysteine residue delivers the catalytic proton directly to the organic leaving group. Instead, the calculations support a two-step mechanism in which Cys96 or Cys159 first donates a proton to Asp99, enabling coordination of two thiolates with R-Hg(II). At the rate-limiting transition state, Asp99 protonates the nascent carbanion in a trigonal planar, bis thiol-ligated R-Hg(II) species to cleave the Hg-C bond and release the hydrocarbon product. Reactions with two other substrates, vinylmercury and cis-2-butenyl-2-mercury, were also modeled, and the computed activation barriers for all three organomercurial substrates reproduce the trend in the experimentally observed enzymatic reaction rates. Analysis of atomic charges in the rate-limiting transition state structure using Natural Population Analysis shows that MerB lowers the activation free energy in the Hg-C protonolysis reaction by redistributing electron density into the leaving group and away from the catalytic proton.

  20. Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya

    PubMed Central

    Deem, Sharon L.; Fèvre, Eric M.; Kinnaird, Margaret; Browne, A. Springer; Muloi, Dishon; Godeke, Gert-Jan; Koopmans, Marion; Reusken, Chantal B.

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%– 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere. PMID:26473733

  1. Meter-scale slopes of candidate MER landing sites from point photoclinometry

    USGS Publications Warehouse

    Beyer, R.A.; McEwen, A.S.; Kirk, R.L.

    2003-01-01

    Photoclinometry was used to analyze the small-scale roughness of areas that fall within the proposed Mars Exploration Rover (MER) 2003 landing ellipses. The landing ellipses presented in this study were those in Athabasca Valles, Elysium Planitia, Eos Chasma, Gusev Crater, Isidis Planitia, Melas Chasma, and Meridiani Planum. We were able to constrain surface slopes on length scales comparable to the image resolution (1.5 to 12 m/pixel). The MER 2003 mission has various engineering constraints that each candidate landing ellipse must satisfy. These constraints indicate that the statistical slope values at 5 m baselines are an important criterion. We used our technique to constrain maximum surface slopes across large swaths of each image, and built up slope statistics for the images in each landing ellipse. We are confident that all MER 2003 landing site ellipses in this study, with the exception of the Melas Chasma ellipse, are within the small-scale roughness constraints. Our results have provided input into the landing hazard assessment process. In addition to evaluating the safety of the landing sites, our mapping of small-scale roughnesses can also be used to better define and map morphologic units. The morphology of a surface is characterized by the slope distribution and magnitude of slopes. In looking at how slopes are distributed, we can better define landforms and determine the boundaries of morphologic units. Copyright 2003 by the American Geophysical Union.

  2. The effects of downwelling radiance on MER surface spectra: the evil that atmospheres do

    NASA Astrophysics Data System (ADS)

    Wolff, M.; Ghosh, A.; Arvidson, R.; Christensen, P.; Guinness, E.; Ruff, S.; Seelos, F.; Smith, M.; Athena Science

    2004-11-01

    While it may not be surprising to some that downwelling radiation in the martian atmosphere may contribute a non-negligible fraction of the radiance for a given surface scene, others remain shocked and surprised (and often dismayed) to discover this fact; particularly with regard to mini-TES observations. Naturally, the relative amplitude of this sky ``contamination'' is often a complicated function of meteorological conditions, viewing geometry, surface properties, and (for the IR) surface temperature. Ideally, one would use a specialized observations to mimic the actual hemispherical-directional nature of the problem. Despite repeated attempts to obtain Pancam complete sky observations and mini-TES sky octants, such observations are not available in the MER observational database. As a result, one is left with the less-enviable, though certainly more computationally intensive, task of connecting point observations (radiance and derived meteorological parameters) to a hemispherical integral of downwelling radiance. Naturally, one must turn to a radiative transfer analysis, despite oft-repeated attempts to assert otherwise. In our presentation, we offer insight into the conditions under which one must worry about atmospheric removal, as well as semi-empirical approaches (based upon said radiative transfer efforts) for producing the correction factors from the available MER atmospheric observations. This work is proudly supported by the MER program through NASA/JPL Contract No. 1242889 (MJW), as well as the contracts for the co-authors.

  3. From Prime to Extended Mission: Evolution of the MER Tactical Uplink Process

    NASA Technical Reports Server (NTRS)

    Michkin, Andrew H.; Laubach, Sharon

    2006-01-01

    To support a 90-day surface mission for two robotic rovers, the Mars Exploration Rover mission designed and implemented an intensive tactical operations process, enabling daily commanding of each rover. Using a combination of new processes, custom software tools, a Mars-time staffing schedule, and seven-day-a-week operations, the MER team was able to compress the traditional weeks-long command-turnaround for a deep space robotic mission to about 18 hours. However, there was never an intention of maintaining the pace of this process indefinitely. Even before the end of the three-month prime mission, MER operations began evolving towards greater sustainability. A combination of continued software tool development, increasing team experience, and availability of reusable sequences first reduced the mean process duration to approximately 11 hours. The number of workshifts required to perform the process dropped, and the team returned to a modified 'Earth-time' schedule. Additional process and tool adaptation eventually provided the option of planning multiple Martian days of activity within a single workshift, making 5- day-a-week operations possible. The vast majority of the science team returned to their home institutions, continuing to participate fully in the tactical operations process remotely. MER has continued to operate for over two Earth-years as many of its key personnel have moved on to other projects, the operations team and budget have shrunk, and the rovers have begun to exhibit symptoms of aging.

  4. Relationship between the persistence of mer operon sequences in Escherichia coli and their resistance to mercury.

    PubMed

    Murtaza, Imtiyaz; Dutt, Amit; Ali, Arif

    2002-03-01

    Studies related to geographic distribution of E. coli carrying mer operon sequences were carried out on the Indian subcontinent. Out of the 80 E. coli isolates, collected from five geographically distinct regions of India, 68 were found to be resistant to one or the other heavy metal used in the study. Among these isolates, 36 were found to be resistant to the inorganic form (HgCl2) and only 5 to resist both the inorganic and organic forms of mercury. Colony hybridization studies revealed 35 isolates out of 68 to hybridize with the probe. Interestingly, some of the mercury-sensitive isolates (Hgs), especially from the Dal Lake, were found positive in hybridization studies. These findings, supported by mercury volatilization studies, indicate the presence of nonfunctional/vestigial mer sequences in the isolates collected from different environments. On the other hand, few of the mercury-resistant isolates (Hgr) from the Yamuna River did not show any sign of hybridization. Further, volatilization studies also indicated an alternate mode of resistance mechanism operating in them. The studies demonstrate that the mer operon sequences share very high homology among the E. coli isolates collected from different geographical locations, and this metal resistance may be a genetic character that arose from a common ancestral background. PMID:11821925

  5. Cutoffs and k-mers: implications from a transcriptome study in allopolyploid plants

    PubMed Central

    2012-01-01

    Background Transcriptome analysis is increasingly being used to study the evolutionary origins and ecology of non-model plants. One issue for both transcriptome assembly and differential gene expression analyses is the common occurrence in plants of hybridisation and whole genome duplication (WGD) and hybridization resulting in allopolyploidy. The divergence of duplicated genes following WGD creates near identical homeologues that can be problematic for de novo assembly and also reference based assembly protocols that use short reads (35 - 100 bp). Results Here we report a successful strategy for the assembly of two transcriptomes made using 75 bp Illumina reads from Pachycladon fastigiatum and Pachycladon cheesemanii. Both are allopolyploid plant species (2n = 20) that originated in the New Zealand Alps about 0.8 million years ago. In a systematic analysis of 19 different coverage cutoffs and 20 different k-mer sizes we showed that i) none of the genes could be assembled across all of the parameter space ii) assembly of each gene required an optimal set of parameter values and iii) these parameter values could be explained in part by different gene expression levels and different degrees of similarity between genes. Conclusions To obtain optimal transcriptome assemblies for allopolyploid plants, k-mer size and k-mer coverage need to be considered simultaneously across a broad parameter space. This is important for assembling a maximum number of full length ESTs and for avoiding chimeric assemblies of homeologous and paralogous gene copies. PMID:22417298

  6. Geology of the MER 2003 "Elysium" candidate landing site in southeastern Utopia Planitia, Mars

    USGS Publications Warehouse

    Tanaka, K.L.; Carr, M.H.; Skinner, J.A.; Gilmore, M.S.; Hare, T.M.

    2003-01-01

    The NASA Mars Exploration Rover (MER) Project has been considering a landing-site ellipse designated EP78B2 in southeastern Utopia Planitia, southwest of Elysium Mons. The site appears to be relatively safe for a MER landing site because of its predicted low wind velocities in mesoscale atmospheric circulation models and its low surface roughness at various scales as indicated by topographic and imaging data sets. Previously, the site's surface rocks have been interpreted to be marine sediments or lava flows. In addition, we suggest that Late Noachian to Early Hesperian collapse and mass wasting of Noachian highland rocks contributed to the deposition of detritus in the area of the ellipse. Furthermore, we document partial Late Hesperian to Early Amazonian resurfacing of the ellipse by flows and vents that may be of mud or silicate volcanic origin. A rover investigation of the Utopia landing site using the MER Athena instrument package might address some fundamental aspects of Martian geologic evolution, such as climate change, hydrologic evolution, and magmatic and tectonic history. Copyright 2003 by the American Geophysical Union.

  7. Avoiding student infection during a Middle East respiratory syndrome (MERS) outbreak: a single medical school experience

    PubMed Central

    2016-01-01

    Purpose: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. Methods: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. Results: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Conclusion: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology. PMID:27240893

  8. Probing high-affinity 11-mer DNA aptamer against Lup an 1 (β-conglutin).

    PubMed

    Nadal, P; Svobodova, M; Mairal, T; O'Sullivan, C K

    2013-11-01

    Aptamers are synthetic nucleic acids with great potential as analytical tools. However, the length of selected aptamers (typically 60-100 bases) can affect affinity, due to the presence of bases not required for interaction with the target, and therefore, the truncation of these selected sequences and identification of binding domains is a critical step to produce potent aptamers with higher affinities and specificities and lowered production costs. In this paper we report the truncation of an aptamer that specifically binds to β-conglutin (Lup an 1), an anaphylactic allergen. Through comparing the predicted secondary structures of the aptamers, a hairpin structure with a G-rich loop was determined to be the binding motif. The highest affinity was observed with a truncation resulting in an 11-mer sequence that had an apparent equilibrium dissociation constant (K D) of 1.7 × 10(-9) M. This 11-mer sequence was demonstrated to have high specificity for β-conglutin and showed no cross-reactivity to other lupin conglutins (α-, δ-, γ-conglutins) and closely related proteins such as gliadin. Finally, the structure of the truncated 11-mer aptamer was preliminarily elucidated, and the GQRS Mapper strongly predicted the presence of a G-quadruplex, which was subsequently corroborated using one-dimensional NMR, thus highlighting the stability of the truncated structure. PMID:24126837

  9. From Prime to Extended Mission: Evolution of the MER Tactical Uplink Process

    NASA Technical Reports Server (NTRS)

    Mishkin, Andrew H.; Laubach, Sharon

    2006-01-01

    To support a 90-day surface mission for two robotic rovers, the Mars Exploration Rover mission designed and implemented an intensive tactical operations process, enabling daily commanding of each rover. Using a combination of new processes, custom software tools, a Mars-time staffing schedule, and seven-day-a-week operations, the MER team was able to compress the traditional weeks-long command-turnaround for a deep space robotic mission to about 18 hours. However, the pace of this process was never intended to be continued indefinitely. Even before the end of the three-month prime mission, MER operations began evolving towards greater sustainability. A combination of continued software tool development, increasing team experience, and availability of reusable sequences first reduced the mean process duration to approximately 11 hours. The number of workshifts required to perform the process dropped, and the team returned to a modified 'Earth-time' schedule. Additional process and tool adaptation eventually provided the option of planning multiple Martian days of activity within a single workshift, making 5-day-a-week operations possible. The vast majority of the science team returned to their home institutions, continuing to participate fully in the tactical operations process remotely. MER has continued to operate for over two Earth-years as many of its key personnel have moved on to other projects, the operations team and budget have shrunk, and the rovers have begun to exhibit symptoms of aging.

  10. Simrank: Rapid and sensitive general-purpose k-mer search tool

    PubMed Central

    2011-01-01

    Background Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available. Results Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset. Conclusions Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity. PMID:21524302

  11. Understanding M-ligand bonding and mer-/fac-isomerism in tris(8-hydroxyquinolinate) metallic complexes.

    PubMed

    Lima, Carlos F R A C; Taveira, Ricardo J S; Costa, José C S; Fernandes, Ana M; Melo, André; Silva, Artur M S; Santos, Luís M N B F

    2016-06-28

    Tris(8-hydroxyquinolinate) metallic complexes, Mq3, are one of the most important classes of organic semiconductor materials. Herein, the nature of the chemical bond in Mq3 complexes and its implications on their molecular properties were investigated by a combined experimental and computational approach. Various Mq3 complexes, resulting from the alteration of the metal and substitution of the 8-hydroxyquinoline ligand in different positions, were prepared. The mer-/fac-isomerism in Mq3 was explored by FTIR and NMR spectroscopy, evidencing that, irrespective of the substituent, mer- and fac-are the most stable molecular configurations of Al(iii) and In(iii) complexes, respectively. The relative M-ligand bond dissociation energies were evaluated experimentally by electrospray ionization tandem mass spectrometry (ESI-MS-MS), showing a non-monotonous variation along the group (Al > In > Ga). The results reveal a strong covalent character in M-ligand bonding, which allows for through-ligand electron delocalization, and explain the preferred molecular structures of Mq3 complexes as resulting from the interplay between bonding and steric factors. The mer-isomer reduces intraligand repulsions, being preferred for smaller metals, while the fac-isomer is favoured for larger metals where stronger covalent M-ligand bonds can be formed due to more extensive through-ligand conjugation mediated by metal "d" orbitals. PMID:27273193

  12. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution

    PubMed Central

    Tang, Xian-Chun; Agnihothram, Sudhakar S.; Jiao, Yongjun; Stanhope, Jeremy; Graham, Rachel L.; Peterson, Eric C.; Avnir, Yuval; Tallarico, Aimee St. Clair; Sheehan, Jared; Zhu, Quan; Baric, Ralph S.; Marasco, Wayne A.

    2014-01-01

    The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers. PMID:24778221

  13. Jamming and percolation in generalized models of random sequential adsorption of linear k -mers on a square lattice

    NASA Astrophysics Data System (ADS)

    Lebovka, Nikolai I.; Tarasevich, Yuri Yu.; Dubinin, Dmitri O.; Laptev, Valeri V.; Vygornitskii, Nikolai V.

    2015-12-01

    The jamming and percolation for two generalized models of random sequential adsorption (RSA) of linear k -mers (particles occupying k adjacent sites) on a square lattice are studied by means of Monte Carlo simulation. The classical RSA model assumes the absence of overlapping of the new incoming particle with the previously deposited ones. The first model is a generalized variant of the RSA model for both k -mers and a lattice with defects. Some of the occupying k adjacent sites are considered as insulating and some of the lattice sites are occupied by defects (impurities). For this model even a small concentration of defects can inhibit percolation for relatively long k -mers. The second model is the cooperative sequential adsorption one where, for each new k -mer, only a restricted number of lateral contacts z with previously deposited k -mers is allowed. Deposition occurs in the case when z ≤(1 -d ) zm where zm=2 (k +1 ) is the maximum numbers of the contacts of k -mer, and d is the fraction of forbidden contacts. Percolation is observed only at some interval kmin≤k ≤kmax where the values kmin and kmax depend upon the fraction of forbidden contacts d . The value kmax decreases as d increases. A logarithmic dependence of the type log10(kmax) =a +b d , where a =4.04 ±0.22 ,b =-4.93 ±0.57 , is obtained.

  14. Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide.

    PubMed

    Paul, Moushumi; Phillips, John G; Renye, John A

    2016-05-01

    An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69μM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure-lowering agent for use in functional foods. PMID:26971162

  15. NMR structural studies reveal a novel protein fold for MerB, the organomercurial lyase involved in the bacterial mercury resistance system.

    PubMed

    Di Lello, Paola; Benison, Gregory C; Valafar, Homayoun; Pitts, Keith E; Summers, Anne O; Legault, Pascale; Omichinski, James G

    2004-07-01

    Mercury resistant bacteria have developed a system of two enzymes (MerA and MerB), which allows them to efficiently detoxify both ionic and organomercurial compounds. The organomercurial lyase (MerB) catalyzes the protonolysis of the carbon-mercury bond resulting in the formation of ionic mercury and a reduced hydrocarbon. The ionic mercury [Hg(II)] is subsequently reduced to the less reactive elemental mercury [Hg(0)] by a specific mercuric reductase (MerA). To better understand MerB's unique enzymatic activity, we used nuclear magnetic resonance (NMR) spectroscopy to determine the structure of the free enzyme. MerB is characterized by a novel protein fold consisting of three noninteracting antiparallel beta-sheets surrounded by six alpha-helices. By comparing the NMR data of free MerB and the MerB/Hg/DTT complex, we identified a set of residues that likely define a Hg/DTT binding site. These residues cluster around two cysteines (C(96) and C(159)) that are crucial to MerB's catalytic activity. A detailed analysis of the structure revealed the presence of an extensive hydrophobic groove adjacent to this Hg/DTT binding site. This extensive hydrophobic groove has the potential to interact with the hydrocarbon moiety of a wide variety of substrates and may explain the broad substrate specificity of MerB. PMID:15222745

  16. Mass dependent stable isotope fractionation of mercury during mer mediated microbial degradation of monomethylmercury

    NASA Astrophysics Data System (ADS)

    Kritee, K.; Barkay, Tamar; Blum, Joel D.

    2009-03-01

    Controlling bioaccumulation of toxic monomethylmercury (MMHg) in aquatic food chains requires differentiation between biotic and abiotic pathways that lead to its production and degradation. Recent mercury (Hg) stable isotope measurements of natural samples suggest that Hg isotope ratios can be a powerful proxy for tracing dominant Hg transforming pathways in aquatic ecosystems. Specifically, it has been shown that photo-degradation of MMHg causes both mass dependent (MDF) and mass independent fractionation (MIF) of Hg isotopes. Because the extent of MDF and MIF observed in natural samples (e.g., fish, soil and sediments) can potentially be used to determine the relative importance of pathways leading to MMHg accumulation, it is important to determine the potential role of microbial pathways in contributing to the fractionation, especially MIF, observed in these samples. This study reports the extent of fractionation of Hg stable isotopes during degradation of MMHg to volatile elemental Hg and methane via the microbial Hg resistance ( mer) pathway in Escherichia coli carrying a mercury resistance ( mer) genetic system on a multi-copy plasmid. During experimental microbial degradation of MMHg, MMHg remaining in reactors became progressively heavier (increasing δ202Hg) with time and underwent mass dependent Rayleigh fractionation with a fractionation factor α202/198 = 1.0004 ± 0.0002 (2SD). However, MIF was not observed in any of the microbial MMHg degradation experiments indicating that the isotopic signature left by mer mediated MMHg degradation is significantly different from fractionation observed during DOC mediated photo-degradation of MMHg. Additionally, a clear suppression of Hg isotope fractionation, both during reduction of Hg(II) and degradation of MMHg, was observed when the cell densities increased, possibly due to a reduction in substrate bioavailability. We propose a multi-step framework for understanding the extent of fractionation seen in our MMHg

  17. A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV

    PubMed Central

    2013-01-01

    Background Evidence points to the emergence of a novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute respiratory syndrome (SARS)-like disease. In response, the development of effective vaccines and therapeutics remains a clinical priority. To accomplish this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV entry inhibitors. Methods In this study, we produced a pseudovirus bearing the full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase-expressing HIV-1 backbone. We then established a pseudovirus-based inhibition assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors. Results Our results demonstrated that the generated MERS-CoV pseudovirus allows for single-cycle infection of a variety of cells expressing dipeptidyl peptidase-4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a recombinant protein containing receptor-binding domain (RBD, residues 377–662) of MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV pseudovirus infection. Conclusion Taken together, the established MERS-CoV inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3 live-virus restrictions and can be used to rapidly screen MERS-CoV entry inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against the highly pathogenic MERS-CoV. PMID:23978242

  18. Percolation and jamming of linear k-mers on a square lattice with defects: Effect of anisotropy.

    PubMed

    Tarasevich, Yuri Yu; Burmistrov, Andrei S; Shinyaeva, Taisiya S; Laptev, Valeri V; Vygornitskii, Nikolai V; Lebovka, Nikolai I

    2015-12-01

    Using the Monte Carlo simulation, we study the percolation and jamming of oriented linear k-mers on a square lattice that contains defects. The point defects with a concentration d are placed randomly and uniformly on the substrate before deposition of the k-mers. The general case of unequal probabilities for orientation of depositing of k-mers along different directions of the lattice is analyzed. Two different relaxation models of deposition that preserve the predetermined order parameter s are used. In the relaxation random sequential adsorption (RRSA) model, the deposition of k-mers is distributed over different sites on the substrate. In the single-cluster relaxation (RSC) model, the single cluster grows by the random accumulation of k-mers on the boundary of the cluster (Eden-like model). For both models, a suppression of growth of the infinite (percolation) cluster at some critical concentration of defects d(c) is observed. In the zero-defect lattices, the jamming concentration p(j) (RRSA model) and the density of single clusters p(s) (RSC model) decrease with increasing length k-mers and with a decrease in the order parameter. For the RRSA model, the value of d(c) decreases for short k-mers (k<16) as the value of s increases. For k=16 and 32, the value of d(c) is almost independent of s. Moreover, for short k-mers, the percolation threshold is almost insensitive to the defect concentration for all values of s. For the RSC model, the growth of clusters with ellipselike shapes is observed for nonzero values of s. The density of the clusters p(s) at the critical concentration of defects d(c) depends in a complex manner on the values of s and k. An interesting finding for disordered systems (s=0) is that the value of p(s) tends towards zero in the limits of the very long k-mers, k→∞, and very small critical concentrations d(c)→0. In this case, the introduction of defects results in a suppression of k-mer stacking and in the formation of empty or loose

  19. Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide

    PubMed Central

    Jiang, Qianqian; Pan, Yu; Cheng, Yupeng; Li, Huiling; Li, Hui

    2016-01-01

    Hepatic ischemia-reperfusion (I-R) injury causes acute organ damage or dysfunction, and remains a problem for liver transplantation. In the I-R phase, the generation of reactive oxygen species aggravates the injury. In the current study, a novel selenocysteine-containing 7-mer peptide (H-Arg-Sec-Gly-Arg-Asn-Ala-Gln-OH) was constructed to imitate the active site of an antioxidant enzyme, glutathione peroxidase (GPX). The 7-mer peptide which has a lower molecular weight, and improved water-solubility, higher stability and improved cell membrane permeability compared with other GPX mimics. Its GPX activity reached 13 U/µmol, which was 13 times that of ebselen (a representative GPX mimic). The effect of this GPX mimic on I-R injury of the liver was assessed in rats. The 7-mer peptide significantly inhibited the increase in serum hepatic amino-transferases, tissue malondialdehyde, nitric oxide contents, myeloperoxidase activity and decrease of GPX activity compared with I-R tissue. Following treatment with the 7-mer peptide, the expression of B-cell CLL/lymphoma-2 (Bcl-2) was significantly upregulated at the mRNA and protein level compared with the I-R group, as determined by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. By contrast, Bcl-2 associated X protein (Bax) was downregulated by the 7-mer peptide compared the I-R group. Histological and ultrastructural changes of the rat liver tissue were also compared among the experimental groups. The results of the current study suggest that the 7-mer peptide protected the liver against hepatic I-R injury via suppression of oxygen-derived free radicals and regulation of Bcl-2 and Bax expression, which are involved in the apoptosis of liver cells. The findings of the present study will further the investigation of the 7-mer peptide as an effective therapeutic agent in hepatic I-R injury. PMID:27431272

  20. [Molecular diagnosis and phylogenetic analysis of the first MERS case in Turkey].

    PubMed

    Bayrakdar, Fatma; Altaş, Ayşe Başak; Korukluoğlu, Gülay; Topal, Selmur

    2015-07-01

    Coronaviruses (CoV) are enveloped, spherical, single-stranded positive-sense RNA viruses causing mainly respiratory and intestinal infections in animals and humans. Until recently five types of human coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, HCoV-229E, SARS-CoV) have been known, however a novel CoV has been identified in 2012 in Saudi Arabia. This virus, namely MERS-CoV (Middle East Respiratory Syndrome Coronavirus), was classified within Coronaviridae family, Coronavirinae sub-family, Betacoronavirus genus, clade C. It causes acute respiratory infections in humans and transmits via respiratory route and close contact between humans. The aim of this study was to present the first MERS case from Turkey identified by molecular methods and the results of viral sequence analysis. A 42-year-old male Turkish citizen who worked as an employee in Jeddah, Kingdom of Saudi Arabia, admitted to hospital with the complaints of fever and malaise on 25-26 September 2014. Since his symptoms went on and got worse, he returned to Turkey, and hospitalized in a hospital's intensive care unit in Hatay on 6th of October with the symptoms of fever, malaise, sweating, cough and respiratory distress. He transferred to a university hospital on 8th of October and died on 11th October. The tracheal aspirate sample obtained before he died was sent to Virology Unit of Reference Laboratories of the Turkish Public Health Institution. Detection of viral RNA was performed by using a commercial real-time PCR kit (hCoV-EMC Real-Time RT-PCR, Fast Track Diagnostics, Luxembourg) targeting the MERS-CoV E protein (upE), ORF1a and ORF1b gene regions. The reference method Superscript III One Step RT-PCR (Invitrogen, USA) recommended by World Health Organization (WHO) was also applied for confirmation. Both of the methods yielded positive results for MERS-CoV RNA. For the amplification of nucleocapsid (N) and RNA-dependent RNA polymerase (RdRp) genes, hemi-nested PCR (Invitrogen, ABD) was conducted

  1. Efficient Design of Compact Unstructured RNA Libraries Covering All k-mers

    PubMed Central

    Orenstein, Yaron

    2016-01-01

    Abstract Current microarray technologies to determine RNA structure or measure protein–RNA interactions rely on single-stranded, unstructured RNA probes on a chip covering together all k-mers. Since space on the array is limited, the problem is to efficiently design a compact library of unstructured ℓ-long RNA probes, where each k-mer is covered at least p times. Ray et al. designed such a library for specific values of k, ℓ, and p using ad-hoc rules. To our knowledge, there is no general method to date to solve this problem. Here, we address the problem of finding a minimum-size covering of all k-mers by ℓ-long sequences with the desired properties for any value of k, ℓ, and p. As we prove that the problem is NP-hard, we give two solutions: the first is a greedy algorithm with a logarithmic approximation ratio; the second, a heuristic greedy approach based on random walks in de Bruijn graphs. The heuristic algorithm works well in practice and produces a library of unstructured RNA probes that is only ∼1.1-times greater in size compared to the theoretical lower bound. We present results for typical values of k and probe lengths ℓ and show that our algorithm generates a library that is significantly smaller than the library of Ray et al.; moreover, we show that our algorithm outperforms naive methods. Our approach can be generalized and extended to generate RNA or DNA oligo libraries with other desired properties. The software is freely available online. PMID:26713687

  2. The Amorphous Component in Martian Basaltic Soil in Global Perspective from MSL and MER Missions

    NASA Technical Reports Server (NTRS)

    Morris, R. V.; Ming, D. W.; Blake, D. F.; Vaniman, D. T.; Bish, D. L.; Chipera, S. J.; Downs, R. T.; Gellert, R.; Treiman, A. H.; Yen, A. S.; Achilles, C. N.; Anderson, R. C.; Bristow, T. F.; Crisp, J. A.; Des Marais, D. J.; Farmer, J. D.; Grotzinger, J. P.; Leshin, L. A.; McAdam, A. C.; Morookian, J. M.; Morrison, S. M.; Rampe, E. B.; Sarrazin, P. C.; Spanovich, N.; Stolper, E. M.

    2013-01-01

    The mineralogy instrument CheMin onboard the MSL rover Curiosity analyzed by transmission XRD [1] the <150 microns size fraction of putative global basaltic martian soil from scoops 4 and 5 of the Rocknest aeolian bedform (sol 81-120). Here, we combine chemical (APXS) and mineralogical (Mossbauer; MB) results from the MER rovers with chemical (APXS) and mineralogical (CheMin) results from Curiosity to constrain the relative proportions of amorphous and crystalline components, the bulk chemical composition of those components, and the

  3. 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling

    PubMed Central

    2015-01-01

    Background. Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, more than 1,300 laboratory confirmed cases of MERS-CoV infections have been reported in Asia, North Africa, and Europe by July 2015. The recent MERS-CoV nosocomial outbreak in South Korea quickly became the second largest such outbreak with 186 total cases and 36 deaths in a little more than one month, second only to Saudi Arabia in country-specific number of reported cases. Methods. We use a simple mathematical model, the Richards model, to trace the temporal course of the South Korea MERS-CoV outbreak. We pinpoint its outbreak turning point and its transmissibility via basic reproduction number R0 in order to ascertain the occurrence of this nosocomial outbreak and how it was quickly brought under control. Results. The estimated outbreak turning point of ti = 23.3 days (95% CI [22.6–24.0]), or 23–24 days after the onset date of the index case on May 11, pinpoints June 3–4 as the time of the turning point or the peak incidence for this outbreak by onset date. R0 is estimated to range between 7.0 and 19.3. Discussion and Conclusion. The turning point of the South Korea MERS-CoV outbreak occurred around May 27–29, when control measures were quickly implemented after laboratory confirmation of the first cluster of nosocomial infections by the index patient. Furthermore, transmissibility of MERS-CoV in the South Korea outbreak was significantly higher than those reported from past MERS-CoV outbreaks in the Middle East, which is attributable to the nosocomial nature of this outbreak. Our estimate of R0 for the South Korea MERS-CoV nosocomial outbreak further highlights the importance and the risk involved in cluster infections and superspreading events in crowded settings such as hospitals. Similar to the 2003 SARS epidemic, outbreaks of infectious diseases with low community transmissibility like MERS-CoV could still occur initially with large clusters of

  4. The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses

    PubMed Central

    Forni, Diego; Filippi, Giulia; Cagliani, Rachele; De Gioia, Luca; Pozzoli, Uberto; Al-Daghri, Nasser; Clerici, Mario; Sironi, Manuela

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function. PMID:26404138

  5. Effects of APP 5-mer peptide analogue P165 on the synaptic proteins and insulin signal transduction proteins

    PubMed Central

    Feng, Bo; Hu, Peng; Lu, Shu-Jun; Wang, Rong; Du, Yi-Feng

    2014-01-01

    Diabetic encephalopathy (DE) is one of risk factors for Alzheimer’s disease (AD). Our previous findings indicated that DE animals had impairment of learning and memory and degeneration of hippocampal neurons, which could be improved by neurotrophic peptide. APP 17-mer peptide is a synthesized peptide sequenced from soluble amyloid precursor protein. APP 17-mer peptide has neural protective effect, but is susceptible to enzyme degradation. Soluble APP 5-mer peptide is the active form of APP 17-mer peptide, and composed of arginine, glutamic acid, arginine, methionine and serine. P165, an APP 5-mer peptide analog reconstructed by our lab, is resistant to enzyme degradation, and can be orally used to protect neurons. In the present study, high glucose and Aβ25-35 were used to cause injury to human neuroblastoma cell line SH-SY5Y in vitro, and streptozotocin was used to induce diabetes in mice in vivo. The changes in synaptic proteins and proteins of insulin signal transduction which closely correlate with learning and memory were detected in these cells and the brain of mice. Results showed that P165 could up-regulate the expression of α-synuclein and insulin receptor (IR), down-regulate the expression of insulin receptor substrate-1 (IRS-1), PSD-95, Shank1 and MAPK expression. All these findings suggest that nicorandil might be a potential drug used for the treatment of AD. PMID:24753747

  6. Transport of localized and extended excitations in chains embedded with randomly distributed linear and nonlinear n -mers

    NASA Astrophysics Data System (ADS)

    López-González, Dany; Molina, Mario I.

    2016-03-01

    We examine the transport of extended and localized excitations in one-dimensional linear chains populated by linear and nonlinear symmetric identical n -mers (with n =3 , 4, 5, and 6), randomly distributed. First, we examine the transmission of plane waves across a single linear n -mer, paying attention to its resonances, and looking for parameters that allow resonances to merge. Within this parameter regime we examine the transmission of plane waves through a disordered and nonlinear segment composed by n -mers randomly placed inside a linear chain. It is observed that nonlinearity tends to inhibit the transmission, which decays as a power law at long segment lengths. This behavior still holds when the n -mer parameters do not obey the resonance condition. On the other hand, the mean square displacement exponent of an initially localized excitation does not depend on nonlinearity at long propagation distances z , and shows a superdiffusive behavior ˜z1.8 for all n -mers, when parameters obey the resonance merging condition; otherwise the exponent reverts back to the random dimer model value ˜z1.5 .

  7. Application of State Analysis and Goal-based Operations to a MER Mission Scenario

    NASA Technical Reports Server (NTRS)

    Morris, John Richard; Ingham, Michel D.; Mishkin, Andrew H.; Rasmussen, Robert D.; Starbird, Thomas W.

    2006-01-01

    State Analysis is a model-based systems engineering methodology employing a rigorous discovery process which articulates operations concepts and operability needs as an integrated part of system design. The process produces requirements on system and software design in the form of explicit models which describe the system behavior in terms of state variables and the relationships among them. By applying State Analysis to an actual MER flight mission scenario, this study addresses the specific real world challenges of complex space operations and explores technologies that can be brought to bear on future missions. The paper first describes the tools currently used on a daily basis for MER operations planning and provides an in-depth description of the planning process, in the context of a Martian day's worth of rover engineering activities, resource modeling, flight rules, science observations, and more. It then describes how State Analysis allows for the specification of a corresponding goal-based sequence that accomplishes the same objectives, with several important additional benefits.

  8. Evaluation of 50-mer oligonucleotide arrays for detectingmicrobial populations in environmental samples.

    SciTech Connect

    Tiquia, S.M.; Wu, L.; Chong, S.C.; Passovets, S.; Xu, D.; Xu, Y.; Zhou, J.

    2004-03-30

    Microarrays fabricated with oligonucleotides longer than 40bp have been introduced for monitoring whole genome expression but havenot been evaluated with environmental samples. To determine the potentialof this type of microarray for environmental studies, a 50-meroligonucleotide microarray was constructed using 763 genes involved innitrogen cycling: nitrite reductase (nirS and nirK), ammoniamonooxygenase (amoA), nitrogenase (nifH), methane monooxygenase (pmoA),and sulfite reductase (dsrAB) from public databases and our own sequencecollections. The comparison of the sequences from pure cultures indicatedthat the developed microarrays could provide species-level resolution foranalyzing microorganisms involved in nitrification, denitrification,nitrogen fixation, methane oxidation, and sulfite reduction. Sensitivitytests suggested that the 50-mer oligonucleotide arrays could detectdominant populations in the environments, although sensitivity stillneeds to be improved. A significant quantitative relationship was alsoobtained with a mixture of DNAs from eight different bacteria. Theseresults suggest that the 50-mer oligonucleotide array can be used as aspecific and quantitative parallel tool for the detection of microbialpopulations in environmental samples.

  9. Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses.

    PubMed

    Cioni, M; Leboeuf, C; Comoli, P; Ginevri, F; Hirsch, H H

    2016-04-01

    Uncontrolled BK polyomavirus (BKPyV) replication in kidney transplant recipients (KTRs) causes polyomavirus-associated nephropathy and allograft loss. Reducing immunosuppression is associated with clearing viremia and nephropathy and increasing BKPyV-specific T cell responses in most patients; however, current immunoassays have limited sensitivity, target mostly CD4(+) T cells, and largely fail to predict onset and clearance of BKPyV replication. To characterize BKPyV-specific CD8(+) T cells, bioinformatics were used to predict 9mer epitopes in the early viral gene region (EVGR) presented by 14 common HLAs in Europe and North America. Thirty-nine EVGR epitopes were experimentally confirmed by interferon-γ enzyme-linked immunospot assays in at least 30% of BKPyV IgG-seropositive healthy participants. Most 9mers clustered in domains, and some were presented by more than one HLA class I, as typically seen for immunodominant epitopes. Specific T cell binding using MHC class I streptamers was demonstrated for 21 of 39 (54%) epitopes. In a prospective cohort of 118 pediatric KTRs, 19 patients protected or recovering from BKPyV viremia were experimentally tested, and 13 epitopes were validated. Single HLA mismatches were not associated with viremia, suggesting that failing immune control likely involves multiple factors including maintenance immunosuppression. Combining BKPyV load and T cell assays using immunodominant epitopes may help in evaluating risk and reducing immunosuppression and may lead to safe adoptive T cell transfer. PMID:26663765

  10. A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells.

    PubMed

    Monteiro, Claudia; Pinheiro, Marina; Fernandes, Mariana; Maia, Sílvia; Seabra, Catarina L; Ferreira-da-Silva, Frederico; Reis, Salette; Gomes, Paula; Martins, M Cristina L

    2015-08-01

    Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78. PMID:26066462

  11. The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV)

    PubMed Central

    Milne-Price, Shauna; Miazgowicz, Kerri L.; Munster, Vincent J.

    2014-01-01

    On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China’s Guangdong Province and affected more than 8000 patients in 26 countries before it was contained six months later. Over a year after the emergence of this novel coronavirus—Middle East Respiratory Syndrome coronavirus (MERS-CoV)—it has caused 178 laboratory confirmed cases and 76 deaths The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features and intervention strategies of the novel coronavirus, MERS-CoV. PMID:24585737

  12. A lesson learned from Middle East respiratory syndrome (MERS) in Saudi Arabia.

    PubMed

    Al Shehri, Ali M

    2015-04-01

    Middle East respiratory syndrome (MERS) caused by novel Corona virus hit Kingdom of Saudi Arabia (KSA) and resulted in hundreds of mortality and morbidity, fears and psychosocial stress among population, economic loss and major political change at Ministry of Health (MoH). Although MERS discovered two years ago, confusion still exists about its origin, nature, and consequences. In 2003, similar virus (SARS) hit Canada and resulted in a reform of Canada's public health system and creation of a Canadian Agency for Public Health, similar to the US Centers for Disease Control (CDC). The idea of Saudi CDC is attractive and even "sexy" but it is not the best option. Experience and literature indicate that the best option for KSA is to revitalize national public health systems on the basis of comprehensive, continuing, and integrated primary health care (PHC) and public health (PH). This article proposes three initial, but essential, steps for such revitalization to take place: political will and support, integration of PHC and PH, and on-job professional programs for the workforce. In addition, current academic and training programs for PHC and PH should be revisited in the light of national vision and strategy that aim for high quality products that protect and promote healthy nation. Scientific associations, medical education research chair, and relevant academic bodies should be involved in the revitalization to ensure quality of process and outcomes. PMID:25803593

  13. Seasonal Variation of Aerosol Particle Size Using MER/Pancam Sky Imaging

    NASA Astrophysics Data System (ADS)

    Smith, M. D.; Wolff, M. J.

    2013-12-01

    Imaging of the sky taken by the Pancam cameras on-board the Mars Exploration Rovers (MER) provide a useful tool for determining the optical depth and physcial properties of aerosols above the rover. Specifically, the brightness of the sky as a function of angle away from the Sun provides a powerful constraint on the size distribution and shape of dust and water ice aerosols. More than 100 Pancam "sky surveys" were taken by each of the two MER rovers covering a time span of several Mars years and a wide range of dust loading conditions including the planet-encirclind dust storm during Mars Year 28 (Earth year 2007). These sky surveys enable the time evolution of aerosol particle size to be determined including its relation to dust loading. Radiative transfer modeling is used to model the observations. Synthetic Pancam sky brightness is computed using a discrete-ordinates radiative transfer code that accounts for multiple scattering from aerosols and spherical geometry by integrating the source functions along curved paths in that coordinate system. We find that Mie scattering from spheres is not a good approximation for describing the angular variation of sky brightness far from the Sun (at scattering angles greater than 45 degrees). Significant seasonal variations are seen in the retrieved effective radius of the aerosols with higher optical depth strongly correlated with larger particle size.

  14. High-Resolution Topomapping of Mars: Life After MER Site Selection

    NASA Technical Reports Server (NTRS)

    Kirk, R. L.; Howington-Kraus, E.; Hare, T. M.; Soricone, R.; Ross, K.; Weller, L.; Rosiek, M.; Redding, B.; Galuszka, D.; Haldemann, A. F. C.

    2004-01-01

    In this abstract we describe our ongoing use of high-resolution images from the Mars Global Surveyor Mars Orbiter Camera Narrow-Angle subsystem (MGS MOC-NA) to derive quantitative topographic and slope data for the martian surface at 3 - 10-m resolution. Our efforts over the past several years focused on assessment of candidate landing sites for the Mars Exploration Rovers (MER) and culminated in the selection of sites in Gusev crater and Meridiani Planum as safe as well as scientifically compelling. As of this writing, MER-A (Spirit) has landed safely in Gusev and we are performing a limited amount of additional mapping near the landing point to support localization of the lander and rover operations planning. The primary focus of our work, however, has been extending our techniques to sample a variety of geologic terrains planetwide to support both a variety of geoscientific studies and planning and data analysis for missions such as Mars Express, Mars Reconnaissance Orbiter, and Phoenix.

  15. MERS-CoV in Upper Respiratory Tract and Lungs of Dromedary Camels, Saudi Arabia, 2013–2014

    PubMed Central

    Khalafalla, Abdelmalik I.; Lu, Xiaoyan; Al-Mubarak, Abdullah I.A.; Dalab, Abdul Hafeed S.; Al-Busadah, Khalid A.S.

    2015-01-01

    To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1–2 month intervals from 2 independent groups of animals during April 2013–May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Of 96 live camels, 28 (29.2%) nasal swab samples were positive; of 91 camel carcasses, 56 (61.5%) lung tissue samples were positive. Positive samples were more commonly found among young animals (<4 years of age) than adults (>4 years of age). The proportions of positive samples varied by month for both groups; detection peaked during November 2013 and January 2014 and declined in March and May 2014. These findings further our understanding of MERS-CoV infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections. PMID:26079346

  16. Overview of preparedness and response for Middle East respiratory syndrome coronavirus (MERS-CoV) in Oman.

    PubMed

    Al-Abaidani, I S; Al-Maani, A S; Al-Kindi, H S; Al-Jardani, A K; Abdel-Hady, D M; Zayed, B E; Al-Harthy, K S; Al-Shaqsi, K H; Al-Abri, S S

    2014-12-01

    Several countries in the Middle East and around 22 countries worldwide have reported cases of human infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). The exceptionally high fatality rate resulting from MERS-CoV infection in conjunction with the paucity of knowledge about this emerging virus has led to major public and international concern. Within the framework of the national acute respiratory illness surveillance, the Ministry of Health in the Sultanate of Oman has announced two confirmed cases of MERS-CoV to date. The aim of this report is to describe the epidemiological aspects of these two cases and to highlight the importance of public health preparedness and response. The absence of secondary cases among contacts of the reported cases can be seen as evidence of the effectiveness of infection prevention and control precautions as an important pillar of the national preparedness and response plan applied in the health care institutions in Oman. PMID:25447719

  17. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    NASA Technical Reports Server (NTRS)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  18. Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease

    PubMed Central

    Ho, Bo-Lin; Cheng, Shu-Chun; Shi, Lin; Wang, Ting-Yun; Ho, Kuan-I; Chou, Chi-Yuan

    2015-01-01

    Background A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1st October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (Mpro) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. Methods and Results The crystal structure of MERS-CoV Mpro indicates that it shares a similar scaffold to that of other coronaviral Mpro and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV Mpro undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV Mpro is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. Conclusions MERS-CoV Mpro shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral Mpro family. PMID:26658006

  19. Allosteric underwinding of DNA is a critical step in positive control of transcription by Hg-MerR

    NASA Astrophysics Data System (ADS)

    Ansari, Aseem Z.; Chael, Mark L.; O'Halloran, Thomas V.

    1992-01-01

    POSITIVE control of transcription often involves stimulatory protein-protein interactions between regulatory factors and RNA polymerase1. Critical steps in the activation process itself are seldom ascribed to protein-DNA distortions. Activator-induced DNA bending is typically assigned a role in binding-site recognition2, alterations in DNA loop structures3 or optimal positioning of the activator for interaction with polymerase4. Here we present a transcriptional activation mechanism that does not require a signal-induced DNA bend but rather a receptor-induced untwisting of duplex DNA. The allosterically modulated transcription factor MerR is a represser and an Hg(II)-responsive activator of bacterial mercury-resistance genes5-7.Escherichia coliRNA polymerase binds to the MerR-promoter complex but cannot proceed to a transcriptionally active open complex until Hg(II) binds to MerR (ref. 6). Chemical nuclease studies show that the activator form, but not the represser, induces a unique alteration of the helical structure localized at the centre of the DNA-binding site6. Data presented here indicate that this Hg-MerR-induced DNA distortion corresponds to a local underwinding of the spacer region of the promoter by about 33° relative to the MerR-operator complex. The magnitude and the direction of the Hg-MerR-induced change in twist angle are consistent with a positive control mechanism involving reorientation of conserved, but suboptimally phased, promoter elements and are consistent with a role for torsional stress in formation of an open complex.

  20. Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry

    SciTech Connect

    Song, Wenfei; Wang, Ying; Wang, Nianshuang; Wang, Dongli; Guo, Jianying; Fu, Lili; Shi, Xuanling

    2014-12-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection. - Highlights: • It has been demonstrated that MERS-CoV infects host cells through binding its envelope spike (S) glycoprotein to the host cellular receptor dipeptidyl peptidase 4 (DPP4). • To identify the critical residues on hDPP4 for RBD binding and virus entry, we constructed a panel of hDPP4 mutants based on structure-guided mutagenesis. • Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues on hDPP4 had significant impacts on virus/receptor interactions and viral entry. • Our study has provided new insights into the features of interactions between hDPP4 and MERS-CoV RBD, and provides potential explanation for cellular and species tropism of MERS-CoV infection.

  1. Jamming and percolation in generalized models of random sequential adsorption of linear k-mers on a square lattice.

    PubMed

    Lebovka, Nikolai I; Tarasevich, Yuri Yu; Dubinin, Dmitri O; Laptev, Valeri V; Vygornitskii, Nikolai V

    2015-12-01

    The jamming and percolation for two generalized models of random sequential adsorption (RSA) of linear k-mers (particles occupying k adjacent sites) on a square lattice are studied by means of Monte Carlo simulation. The classical RSA model assumes the absence of overlapping of the new incoming particle with the previously deposited ones. The first model is a generalized variant of the RSA model for both k-mers and a lattice with defects. Some of the occupying k adjacent sites are considered as insulating and some of the lattice sites are occupied by defects (impurities). For this model even a small concentration of defects can inhibit percolation for relatively long k-mers. The second model is the cooperative sequential adsorption one where, for each new k-mer, only a restricted number of lateral contacts z with previously deposited k-mers is allowed. Deposition occurs in the case when z≤(1-d)z(m) where z(m)=2(k+1) is the maximum numbers of the contacts of k-mer, and d is the fraction of forbidden contacts. Percolation is observed only at some interval k(min)≤k≤k(max) where the values k(min) and k(max) depend upon the fraction of forbidden contacts d. The value k(max) decreases as d increases. A logarithmic dependence of the type log(10)(k(max))=a+bd, where a=4.04±0.22,b=-4.93±0.57, is obtained. PMID:26764641

  2. Distinct Immune Response in Two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside?

    PubMed Central

    Goffard, Anne; Fournier, Clement; Kipnis, Eric; Titecat, Marie; Bortolotti, Perinne; Martinez, Laura; Dubucquoi, Sylvain; Dessein, Rodrigue; Gosset, Philippe; Mathieu, Daniel; Guery, Benoit

    2014-01-01

    One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection. PMID:24551142

  3. The Planning, Programming, Budgeting, and Evaluation System of the Board of Education for the Borough of York. Management of Educational Resources System (MERS). Progress Report Number One.

    ERIC Educational Resources Information Center

    York Borough Board of Education, Toronto (Ontario).

    Three aspects of the York Borough's school instructional programs are discussed: program structure, program costs, and program evaluation. Some basic philosophies of the Management of Educational Resources System (MERS) are set forth and the early history of the project is described showing how the boardwide MERS evolved from a pilot experiment…

  4. HYBRIDIZATION OF DNA PROBES WITH WHOLE-COMMUNITY GENOMES FOR DETECTION OF GENES THAT ENCODE MICROBIAL RESPONSES TO POLLUTANTS: MER GENES AND HG2+ RESISTANCE

    EPA Science Inventory

    Nucleic acids extracted from microbial biomass were hybridized with probes representing four mer operons, to detect genes encoding adaptation to Hg2+. An enrichment in sequences similar to the mer genes of transposon 501 occurred during adaptation in a freshwater community. In an...

  5. Up-Regulation of Soluble Axl and Mer Receptor Tyrosine Kinases Negatively Correlates with Gas6 in Established Multiple Sclerosis Lesions

    PubMed Central

    Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget

    2009-01-01

    Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (∼150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity. PMID:19541935

  6. Crystal Structures of the Organomercurial Lyase MerB in Its Free and Mercury-bound Forms: INSIGHTS INTO THE MECHANISM OF METHYLMERCURY DEGRADATION

    SciTech Connect

    Lafrance-Vanasse, Julien; Lefebvre, Maryse; Lello, Paola Di; Sygusch, Jurgen; Omichinski, James G. )

    2009-01-27

    Bacteria resistant to methylmercury utilize two enzymes (MerA and MerB) to degrade methylmercury to the less toxic elemental mercury. The crucial step is the cleavage of the carbon-mercury bond of methylmercury by the organomercurial lyase (MerB). In this study, we determined high resolution crystal structures of MerB in both the free (1.76-{angstrom} resolution) and mercury-bound (1.64-{angstrom} resolution) states. The crystal structure of free MerB is very similar to the NMR structure, but important differences are observed when comparing the two structures. In the crystal structure, an amino-terminal {alpha}-helix that is not present in the NMR structure makes contact with the core region adjacent to the catalytic site. This interaction between the amino-terminal helix and the core serves to bury the active site of MerB. The crystal structures also provide detailed insights into the mechanism of carbon-mercury bond cleavage by MerB. The structures demonstrate that two conserved cysteines (Cys-96 and Cys-159) play a role in substrate binding, carbon-mercury bond cleavage, and controlled product (ionic mercury) release. In addition, the structures establish that an aspartic acid (Asp-99) in the active site plays a crucial role in the proton transfer step required for the cleavage of the carbon-mercury bond. These findings are an important step in understanding the mechanism of carbon-mercury bond cleavage by MerB.

  7. MER Field Geologic Traverse in Gusev Crater, Mars: Initial Results From the Perspective of Spirit

    NASA Technical Reports Server (NTRS)

    Crumpler, L.; Cabrol, N.; desMarais, D.; Farmer, J.; Golmbek, M.; Grant, J.; Greely, R.; Grotzinger, J.; Haskin, L.; Arvidson, R.

    2004-01-01

    This report casts the initial results of the traverse and science investigations by the Mars Exploration Rover (MER) Spirit at Gusev crater [1] in terms of data sets commonly used in field geologic investigations: Local mapping of geologic features, analyses of selected samples, and their location within the local map, and the regional context of the field traverse in terms of the larger geologic and physiographic region. These elements of the field method are represented in the MER characterization of the Gusev traverse by perspective-based geologic/morphologic maps, the placement of the results from Mossbauer, APXS, Microscopic Imager, Mini-TES and Pancam multispectral studies in context within this geologic/ morphologic map, and the placement of the overall traverse in the context of narrow-angle MOC (Mars Orbiter Camera) and descent images. A major campaign over a significance fraction of the mission will be the first robotic traverse of the ejecta from a Martian impact crater along an approximate radial from the crater center. The Mars Exploration Rovers have been conceptually described as 'robotic field geologists', that is, a suite of instruments with mobility that enables far-field traverses to multiple sites located within a regional map/image base at which in situ analyses may be done. Initial results from MER, where the field geologic method has been used throughout the initial course of the investigation, confirm that this field geologic model is applicable for remote planetary surface exploration. The field geologic method makes use of near-field geologic characteristics ('outcrops') to develop an understanding of the larger geologic context through continuous loop of rational steps focused on real-time hypothesis identification and testing. This poster equates 'outcrops' with the locations of in situ investigations and 'regional context' with the geology over distance of several kilometers. Using this fundamental field geologic method, we have

  8. Environmental Conditions Constrain the Distribution and Diversity of Archaeal merA in Yellowstone National Park, Wyoming, U.S.A.

    USGS Publications Warehouse

    Wang, Y.; Boyd, E.; Crane, S.; Lu-Irving, P.; Krabbenhoft, D.; King, S.; Dighton, J.; Geesey, G.; Barkay, T.

    2011-01-01

    The distribution and phylogeny of extant protein-encoding genes recovered from geochemically diverse environments can provide insight into the physical and chemical parameters that led to the origin and which constrained the evolution of a functional process. Mercuric reductase (MerA) plays an integral role in mercury (Hg) biogeochemistry by catalyzing the transformation of Hg(II) to Hg(0). Putative merA sequences were amplified from DNA extracts of microbial communities associated with mats and sulfur precipitates from physicochemically diverse Hg-containing springs in Yellowstone National Park, Wyoming, using four PCR primer sets that were designed to capture the known diversity of merA. The recovery of novel and deeply rooted MerA lineages from these habitats supports previous evidence that indicates merA originated in a thermophilic environment. Generalized linear models indicate that the distribution of putative archaeal merA lineages was constrained by a combination of pH, dissolved organic carbon, dissolved total mercury and sulfide. The models failed to identify statistically well supported trends for the distribution of putative bacterial merA lineages as a function of these or other measured environmental variables, suggesting that these lineages were either influenced by environmental parameters not considered in the present study, or the bacterial primer sets were designed to target too broad of a class of genes which may have responded differently to environmental stimuli. The widespread occurrence of merA in the geothermal environments implies a prominent role for Hg detoxification in these environments. Moreover, the differences in the distribution of the merA genes amplified with the four merA primer sets suggests that the organisms putatively engaged in this activity have evolved to occupy different ecological niches within the geothermal gradient. ?? 2011 Springer Science+Business Media, LLC.

  9. Biophysical characterization of the MerP-like amino-terminal extension of the mercuric reductase from Ralstonia metallidurans CH34.

    PubMed

    Rossy, Emmanuel; Champier, Ludovic; Bersch, Beate; Brutscher, Bernhard; Blackledge, Martin; Covès, Jacques

    2004-01-01

    The purified native mercuric reductase (MerA) from Ralstonia metallidurans CH34 contains an N-terminal sequence of 68 amino acids predicted to be homologous to MerP, the periplasmic mercury-binding protein. This MerP-like protein has now been expressed independently. The protein was named MerAa by homology with Ccc2a, the first soluble domain of the copper-transporting ATPase from yeast. Deltaa has been characterized using a set of biophysical techniques. The binding of mercury was followed using circular dichroism spectroscopy and electrospray mass spectrometry. The two cysteine residues contained in the consensus sequence GMTC XXC are involved in the binding of one mercury atom, with an apparent affinity comparable to that of MerP for the same metal. The metal-binding site is confirmed by NMR chemical shift changes observed between apo- and metal-bound MerAa in solution. NMR shift and NOE data also indicate that only minor structural changes occur upon metal binding. Further NMR investigation of the fold of MerAa using long-range methyl-methyl NOE and backbone residual dipolar coupling data confirm the expected close structural homology with MerP. (15)N relaxation data show that MerAa is a globally rigid molecule. An increased backbone mobility was observed for the loop region connecting the first beta-strand and the first alpha-helix and comprising the metal-binding domain. Although significantly reduced, this loop region keeps some conformational flexibility upon metal binding. Altogether, our data suggest a role of MerAa in mercury trafficking. PMID:14624351

  10. Contributions from Particles in Europe (PiE) 2010, Villefranche-sur-Mer, France: an introduction

    NASA Astrophysics Data System (ADS)

    Mikkelsen, Ole A.; Chami, Malik; Doxaran, David

    2012-04-01

    This special issue of Geo-Marine Letters presents selected contributions from the international conference Particles in Europe (PiE) 2010 organized by Sequoia Scientific, Inc., and the Laboratoire d'Océanographie de Villefranche (LOV) on 15-17 November 2010 in Villefranche-sur-Mer, France, and guest-edited by Ole Mikkelsen, Malik Chami and David Doxaran. PiE was initiated in 2008, in order to promote and further our understanding of the importance of suspended particulate matter (SPM) for a very wide range of processes in the aquatic environment—from optics and acoustics, over sediment transport, to the global carbon balance. The papers in this special issue are in particular concerned with the interaction between SPM and water optical properties, as well as how to use optical proxy measurements to understand SPM processes. The next PiE conference is scheduled for 17-19 October 2012 in Barcelona, Spain.

  11. Mineralogy Considerations for 2003 MER Site Selection and the Importance for Astrobiology

    NASA Technical Reports Server (NTRS)

    Bishop, J. L.

    2001-01-01

    Much of the discussion of site selection on Mars is based on interesting images of the surface combined with safety issues. I argue that the two rovers should be sent to mineralogically distinct regions. Compositional information is still poorly constrained on Mars; however, the instruments on the 2003 Mars Exploration Rovers (MERs) will provide a unique opportunity for detailed characterization including mineral identification. There is strong motivation for sending one rover to a "typical" region on Mars to be used as a ground truth for the Thermal Emission Spectrometer (TES), while the other rover should be sent to a site where water and chemical alteration are likely to have occurred. Determining the mineralogy of the Martian surface material provides information about the past and present environments on Mars which are an integral aspect of whether or not Mars was suitable for the origin of life. Understanding the mineralogy of terrestrial samples from potentially Mars-like environments is essential to this effort.

  12. Results from Automated Cloud and Dust Devil Detection Onboard the MER

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Castano, Rebecca; Bornstein, Benjamin; Fukunaga, Alex; Castano, Andres; Biesiadecki, Jeffrey; Greeley, Ron; Whelley, Patrick; Lemmon, Mark

    2008-01-01

    We describe a new capability to automatically detect dust devils and clouds in imagery onboard rovers, enabling downlink of just the images with the targets or only portions of the images containing the targets. Previously, the MER rovers conducted campaigns to image dust devils and clouds by commanding a set of images be collected at fixed times and downloading the entire image set. By increasing the efficiency of the campaigns, more campaigns can be executed. Software for these new capabilities was developed, tested, integrated, uploaded, and operationally checked out on both rovers as part of the R9.2 software upgrade. In April 2007 on Sol 1147 a dust devil was automatically detected onboard the Spirit rover for the first time. We discuss the operational usage of the capability and present initial dust devil results showing how this preliminary application has demonstrated the feasibility and potential benefits of the approach.

  13. THEMIS Observations, Discoveries and Predictions for the MER A Landing Site in Gusev Crater

    NASA Astrophysics Data System (ADS)

    Rice, J. W.; Christensen, P. R.

    2003-12-01

    THEMIS has "followed the water" and discovered the youngest water flow into the MER A landing site in Gusev crater. This flow has a rumpled looking texture and is interpreted to be viscous material emanating from the mouth of Ma'adim Vallis. The flow can be traced for over 150 km across the floor of Gusev. This flow is emplaced on top of the smooth plains material and covers the whole western half of the landing ellipse. The flow does not show up in THEMIS IR indicating that it is mantled with at least a few cm of dust. This flow is either a debris flow (15-40% water volume content) or hyperconcentrated flow (40-80% water volume content) and not a lava flow based on its morphology, geologic setting, and lack of nearby volcanic sources. Debris flow deposits can be differentiated from hyperconcentrated flows on the basis of particle sorting, sedimentary structures, and inferred rheological properties. Access to this deposit will allow sampling of the most recent water related sediment in the basin. A very interesting relationship has been found to exist for many craters in the region of Gusev. These craters contain stacks of layered sedimentary deposits. It should be noted that these craters lack a large inflowing channel system. A similar layered morphology is seen on the floor of Gusev, especially the SE portion of the crater, where a 190 m thick deposit is being eroded. We propose that this material in Gusev is the remnant of a formerly more extensive regional unit related to the layered deposits seen in the many nearby craters. This observation suggests that the region was formerly buried by several hundred meters of material that is now being exhumed. This also implies that Ma'adim Vallis was a superposed channel that cut down from above and across Gusev. We also offer another scenario for Gusev in that it received periodic outwash deposits and may have contained shallow ephemeral playas with short lifetimes and not deep long lived lakes as suggested by some

  14. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.

    PubMed

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  15. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer. 177.1050 Section 177.1050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...

  16. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer. 177.1050 Section 177.1050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...

  17. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer. 177.1050 Section 177.1050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...

  18. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

    PubMed Central

    de Wit, Emmie; Rasmussen, Angela L.; Falzarano, Darryl; Bushmaker, Trenton; Brining, Douglas L.; Fischer, Elizabeth R.; Martellaro, Cynthia; Okumura, Atsushi; Chang, Jean; Scott, Dana; Benecke, Arndt G.; Katze, Michael G.; Feldmann, Heinz; Munster, Vincent J.

    2013-01-01

    In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 106 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission. PMID:24062443

  19. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

    PubMed Central

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  20. The Miniaturized Moessbauer Spectrometers MIMOS II on MER: Four Years of Operation - A Summary

    NASA Technical Reports Server (NTRS)

    Fleischer, I.; Klingelhoefer, G.; Morris, R. V.; Rodionov, D.; Blumers, M.; Bernhardt, B.; Schroeder, C.; Ming, D. W.; Yen, A. S.; Cohen, B. A.; McCoy, T. J.; Mittlefehldt, D. W.; Schmidt, M. E.; Girones Lopez, J.; Studlek, G.; Brueckner, J.; Gellert, R.; d'Uston, C.

    2008-01-01

    The two Miniaturized Moessbauer Spectrometers (MIMOS II) on board the two Mars Exploration Rovers Spirit and Opportunity have now been collecting important scientific data for more than four years. The spectrometers provide information about Fe-bearing mineral phases and determine Fe oxidation states. The total amount of targets analized exceeds 600, the total integration time exceeds 260 days for both rovers. Since landing, more than five half-lives of the Co-57 MB sources have past (intensity at the time of landing approx. 150 mCi). Current integration times are about 50 hours in order to achieve reasonable statistics as opposed to 8 hours at the beginning of the mission. In total, 13 different mineral phases were detected: Olivine, pyroxene, hematite, magnetite and nanophase ferric oxide were detected at both landing sites. At Gusev, ilmenite, goethite, a ferric sulfate phase and a yet unassigned phase (in the rock Fuzzy Smith) were detected. At Meridiani, jarosite, metallic iron in meteoritic samples (kamacite), troilite, and an unassigned ferric phase were detected. Jarosite and goethite are of special interest, as these minerals are indicators for water activity. In this abstract, an overview of Moessbauer results will be given, with a focus on data obtained since the last martian winter. The MER mission has proven that Moessbauer spectroscopy is a valuable tool for the in situ exploration of extraterrestrial bodies and for the study of Febearing samples. The experience gained through the MER mission makes MIMOS II a obvious choice for future missions to Mars and other targets. Currently, MIMOS II is on the scientific payload of two approved future missions: Phobos Grunt (Russian Space Agency; 2009) and ExoMars (European Space Agency; 2013).

  1. One-step, regioselective synthesis of up to 50-mers of RNA oligomers by montmorillonite catalysis.

    PubMed

    Huang, Wenhua; Ferris, James P

    2006-07-12

    5'-Nucleotides of A and U with the phosphate activated with 1-methyladenine generate RNA oligomers containing 40-50 monomers in 1 day in reactions catalyzed by montmorillonite. The corresponding monomers of C give oligomers that are 20-25-mers in length after a 9-day reaction. It was not possible to determine the chain lengths of the oligomers of G since they did not give well-defined bands on gel electrophoresis. Co-oligomers of A and U as well as A, U, G, and C were also prepared. The oligo(A)s formed were separated by gel electrophoresis, and the bands of the 7-39-mers were isolated, the 3',5'-phosphodiester bonds were cleaved by RNase T(2), and the terminal phosphate groups were cleaved with alkaline phosphatase. HPLC analysis revealed that the proportions of A(5)'pp(5)'A, A, A(2)'pA, and A(2)'pA(2)'pA formed were almost the same for the long and shorter oligomers. A similar structure analysis performed on the oligo(U)s established that the proportions of U(5)'pp(5)'U, U, U(2)'pU, U(2)'pU(2)'pU, U(2)'pU(2)'pU(2)'pU, and U(2)'pU(2)'pU(2)'pU(2)'pU did not vary with chain length. The structural analysis of the oligomers of A revealed that 74% of the phosphodiester bonds were 3',5'-linked a value slightly greater than 67% observed when imidazole was the activating group. 61% of the bonds in the U oligomers were 3',5'-linked, which is almost 3 times greater than the 20% measured when imidazole was the activating group. The potential significance of these data to the origin and early evolution of life is discussed. PMID:16819887

  2. Conceptual Design and Architecture of Mars Exploration Rover (MER) for Seismic Experiments Over Martian Surfaces

    NASA Astrophysics Data System (ADS)

    Garg, Akshay; Singh, Amit

    2012-07-01

    Keywords: MER, Mars, Rover, Seismometer Mars has been a subject of human interest for exploration missions for quite some time now. Both rover as well as orbiter missions have been employed to suit mission objectives. Rovers have been preferentially deployed for close range reconnaissance and detailed experimentation with highest accuracy. However, it is essential to strike a balance between the chosen science objectives and the rover operations as a whole. The objective of this proposed mechanism is to design a vehicle (MER) to carry out seismic studies over Martian surface. The conceptual design consists of three units i.e. Mother Rover as a Surrogate (Carrier) and Baby Rovers (two) as seeders for several MEMS-based accelerometer / seismometer units (Nodes). Mother Rover can carry these Baby Rovers, having individual power supply with solar cells and with individual data transmission capabilities, to suitable sites such as Chasma associated with Valles Marineris, Craters or Sand Dunes. Mother rover deploys these rovers in two opposite direction and these rovers follow a triangulation pattern to study shock waves generated through firing tungsten carbide shells into the ground. Till the time of active experiments Mother Rover would act as a guiding unit to control spatial spread of detection instruments. After active shock experimentation, the babies can still act as passive seismometer units to study and record passive shocks from thermal quakes, impact cratering & landslides. Further other experiments / payloads (XPS / GAP / APXS) can also be carried by Mother Rover. Secondary power system consisting of batteries can also be utilized for carrying out further experiments over shallow valley surfaces. The whole arrangement is conceptually expected to increase the accuracy of measurements (through concurrent readings) and prolong life cycle of overall experimentation. The proposed rover can be customised according to the associated scientific objectives and further

  3. Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide.

    PubMed

    Jiang, Qianqian; Pan, Yu; Cheng, Yupeng; Li, Huiling; Li, Hui

    2016-09-01

    Hepatic ischemia-reperfusion (I-R) injury causes acute organ damage or dysfunction, and remains a problem for liver transplantation. In the I-R phase, the generation of reactive oxygen species aggravates the injury. In the current study, a novel selenocysteine-containing 7‑mer peptide (H-Arg-Sec-Gly-Arg-Asn-Ala-Gln-OH) was constructed to imitate the active site of an antioxidant enzyme, glutathione peroxidase (GPX). The 7‑mer peptide which has a lower molecular weight, and improved water‑solubility, higher stability and improved cell membrane permeability compared with other GPX mimics. Its GPX activity reached 13 U/µmol, which was 13 times that of ebselen (a representative GPX mimic). The effect of this GPX mimic on I‑R injury of the liver was assessed in rats. The 7‑mer peptide significantly inhibited the increase in serum hepatic amino‑transferases, tissue malondialdehyde, nitric oxide contents, myeloperoxidase activity and decrease of GPX activity compared with I‑R tissue. Following treatment with the 7‑mer peptide, the expression of B‑cell CLL/lymphoma‑2 (Bcl‑2) was significantly upregulated at the mRNA and protein level compared with the I‑R group, as determined by reverse transcription‑polymerase chain reaction and immunohistochemistry, respectively. By contrast, Bcl‑2 associated X protein (Bax) was downregulated by the 7‑mer peptide compared the I‑R group. Histological and ultrastructural changes of the rat liver tissue were also compared among the experimental groups. The results of the current study suggest that the 7‑mer peptide protected the liver against hepatic I‑R injury via suppression of oxygen‑derived free radicals and regulation of Bcl‑2 and Bax expression, which are involved in the apoptosis of liver cells. The findings of the present study will further the investigation of the 7-mer peptide as an effective therapeutic agent in hepatic I-R injury. PMID:27431272

  4. PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via up-regulating PPAR-γ to increase surface FasL.

    PubMed

    Zhang, Hao; Wei, Tengteng; Jiang, Xia; Li, Zhimin; Cui, Huazhu; Pan, Jiajun; Zhuang, Wei; Sun, Teng; Liu, Zhiwei; Zhang, Zhongming; Dong, Hongyan

    2016-01-01

    Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. However, the underlying mechanism for PEDF and the functional PEDF peptides 34-mer and 44-mer to inhibit angiogenesis in the heart has not been fully established. In the present study, by constructing adult Sprague-Dawley rat models of acute myocardial infarction (AMI) and in vitro myocardial angiogenesis, we showed that PEDF and 34-mer markedly inhibits angiogenesis by selectively inducing tip cells apoptosis rather than quiescent cells. Peptide 44-mer on the other hand exhibits no such effects. Next, we identified Fas death pathway as essential downstream regulators of PEDF and 34-mer activities in inhibiting angiogenesis. By using peroxisome proliferator-activated receptor γ (PPAR-γ) siRNA and PPAR-γ inhibitor, GW9662, we found the effects of PEDF and 34-mer were extensively blocked. These data suggest that PEDF and 34-mer inhibit angiogenesis via inducing tip cells apoptosis at least by means of up-regulating PPAR-γ to increase surface FasL in the ischemic heart, which might be a novel mechanism to understanding cardiac angiogenesis after AMI. PMID:26519036

  5. The Synechocystis PCC6803 MerA-Like Enzyme Operates in the Reduction of Both Mercury and Uranium under the Control of the Glutaredoxin 1 Enzyme

    PubMed Central

    Marteyn, Benoit; Sakr, Samer; Farci, Sandrine; Bedhomme, Mariette; Chardonnet, Solenne; Decottignies, Paulette; Lemaire, Stéphane D.; Cassier-Chauvat, Corinne

    2013-01-01

    In a continuing effort to analyze the selectivity/redundancy of the three glutaredoxin (Grx) enzymes of the model cyanobacterium Synechocystis PCC6803, we have characterized an enzyme system that plays a crucial role in protection against two toxic metal pollutants, mercury and uranium. The present data show that Grx1 (Slr1562 in CyanoBase) selectively interacts with the presumptive mercuric reductase protein (Slr1849). This MerA enzyme plays a crucial role in cell defense against both mercuric and uranyl ions, in catalyzing their NADPH-driven reduction. Like MerA, Grx1 operates in cell protection against both mercury and uranium. The Grx1-MerA interaction requires cysteine 86 (C86) of Grx1 and C78 of MerA, which is critical for its reductase activity. MerA can be inhibited by glutathionylation and subsequently reactivated by Grx1, likely through deglutathionylation. The two Grx1 residues C31, which belongs to the redox active site (CX2C), and C86, which operates in MerA interactions, are both required for reactivation of MerA. These novel findings emphasize the role of glutaredoxins in tolerance to metal stress as well as the evolutionary conservation of the glutathionylation process, so far described mostly for eukaryotes. PMID:23852862

  6. In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection

    PubMed Central

    2013-01-01

    Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. Findings A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. Conclusion Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment. PMID:24364985

  7. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014.

    PubMed

    Reusken, C B; Farag, E A; Jonges, M; Godeke, G J; El-Sayed, A M; Pas, S D; Raj, V S; Mohran, K A; Moussa, H A; Ghobashy, H; Alhajri, F; Ibrahim, A K; Bosch, B J; Pasha, S K; Al-Romaihi, H E; Al-Thani, M; Al-Marri, S A; AlHajri, M M; Haagmans, B L; Koopmans, M P

    2014-01-01

    Antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) were detected in serum and milk collected according to local customs from 33 camels in Qatar, April 2014. At one location, evidence for active virus shedding in nasal secretions and/or faeces was observed for 7/12 camels; viral RNA was detected in milk of five of these seven camels. The presence of MERS-CoV RNA in milk of camels actively shedding the virus warrants measures to prevent putative food-borne transmission of MERS-CoV. PMID:24957745

  8. Evaporative evolution of Martian brines based on halogens in nakhlites and MER samples

    SciTech Connect

    Rao, M.N.; Sutton, S.R.; McKay, D.S.

    2005-02-04

    Comparison of Cl and Br from Nakhla viens to MER samples suggests two kinds of brine solutions existed on Mars, one early and one late in the evaporation sequence. These solutions precipitated the secondary salts at the Meridiani and Gusev sites. We have recently reported the Cl and Br abundances determined by APS X-ray Microprobe and EMPA analyses of secondary aqueous minerals in Nakhla veins and discussed the significance of Cl-Br correlations with respect to the evolution of brine solutions on Mars. In that study, we suggested that the low Br concentration ({approx}10 ppm) in Lafayette Iddingsite is indicative of early stage of evaporation during progressive evolution of Martian brine solutions, which is, in turn, consistent with the petrographic evidence of early deposition of salt sequence of carbonate-sulfate- and no halite in Lafayette. We showed that the high Br concentrations of {approx}240 ppm in secondary salts in Nakhla veins similarly indicate late stages of evaporation in evolving Martian brine solutions which is again consistent with petrographic evidence of late stage deposition of salt sequence i.e. carbonate-sulfate-halite in Nakhla. When sea water evaporates under equilibrium conditions, the most insoluble carbonates (siderite and calcite) deposit first, followed by sulfates (gypsum and anhydrite) and finally the water-soluble halides are precipitated when the water content is sufficiently low. In the present study, we make a detailed comparison of Cl/Br ratios in secondary minerals in nakhlites with those in MER soils and rocks at Gusev and Meridiani and show that the compositions of solutions that inundated Lafayette iddingsite (early stage) and Nakhla veins (late stage) include the range of solution-compositions that gave rise to a variety of secondary salts at Gusev and Meridiani sites. Further, the results obtained here suggest that two kinds of brine solutions (one, late and the other, early or intermediate stage) seem to have inundated

  9. Dust Accumulation and Solar Panel Array Performance on the Mars Exploration Rover (MER) Project

    NASA Technical Reports Server (NTRS)

    Turgay, Eren H.

    2004-01-01

    One of the most fundamental design considerations for any space vehicle is its power supply system. Many options exist, including batteries, fuel cells, nuclear reactors, radioisotopic thermal generators (RTGs), and solar panel arrays. Solar arrays have many advantages over other types of power generation. They are lightweight and relatively inexpensive, allowing more mass and funding to be allocated for other important devices, such as scientific instruments. For Mars applications, solar power is an excellent option, especially for long missions. One might think that dust storms would be a problem; however, while dust blocks some solar energy, it also scatters it, making it diffuse rather than beamed. Solar cells are still able to capture this diffuse energy and convert it into substantial electrical power. For these reasons, solar power was chosen to be used on the 1997 Mars Pathfinder mission. The success of this mission set a precedent, as NASA engineers have selected solar power as the energy system of choice for all future Mars missions, including the Mars Exploration Rover (MER) Project. Solar sells have their drawbacks, however. They are difficult to manufacture and are relatively fragile. In addition, solar cells are highly sensitive to different parts of the solar spectrum, and finding the correct balance is crucial to the success of space missions. Another drawback is that the power generated is not a constant with respect to time, but rather changes with the relative angle to the sun. On Mars, dust accumulation also becomes a factor. Over time, dust settles out of the atmosphere and onto solar panels. This dust blocks and shifts the frequency of the incoming light, degrading solar cell performance. My goal is to analyze solar panel telemetry data from the two MERs (Spirit and Opportunity) in an effort to accurately model the effect of dust accumulation on solar panels. This is no easy process due to the large number of factors involved. Changing solar

  10. Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors.

    PubMed

    Kumar, Vathan; Tan, Kian-Pin; Wang, Ying-Ming; Lin, Sheng-Wei; Liang, Po-Huang

    2016-07-01

    Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents. PMID:27240464