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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. 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…

  3. 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…

  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 Respiratory Syndrome (MERS): Frequently Asked Questions and Answers. Updated ...

  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. 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.

  7. 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

  8. 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.

  9. 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

  10. MERS coronavirus: diagnostics, epidemiology and transmission.

    PubMed

    Mackay, Ian M; Arden, Katherine E

    2015-01-01

    The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20% to 40% of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20% of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited

  11. MERS: emergence of a novel human coronavirus

    PubMed Central

    Raj, V. Stalin; Osterhaus, Albert D.M.E.; Fouchier, Ron A.M.; Haagmans, Bart L.

    2014-01-01

    A novel coronavirus (CoV) that causes a severe lower respiratory tract infection in humans, emerged in the Middle East region in 2012. This virus, named Middle East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs, but other animal species like dromedary camels may potentially act as intermediate hosts by spreading the virus to humans. Although human to human transmission has been demonstrated, analysis of human MERS clusters indicated that chains of transmission were not self-sustaining, especially when infection control was implemented. Thus, timely identification of new MERS cases followed by their quarantine, combined with measures to limit spread of the virus from the (intermediate) host to humans, may be crucial in controlling the outbreak of this emerging CoV. PMID:24584035

  12. 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.

  13. Generation of a tamoxifen inducible Tnnt2MerCreMer knock-in mouse model for cardiac studies

    PubMed Central

    Yan, Jianyun; Sultana, Nishat; Zhang, Lu; Park, David S; Shekhar, Akshay; Hu, Jun; Bu, Lei; Cai, Chen-Leng

    2015-01-01

    Summary Tnnt2, encoding thin-filament sarcomeric protein cardiac troponin T, plays critical roles in heart development and function in mammals. To develop an inducible genetic deletion strategy in myocardial cells, we generated a new Tnnt2:MerCreMer (Tnnt2MerCreMer/+) knock-in mouse. Rosa26 reporter lines were used to examine the specificity and efficiency of the inducible Cre recombinase. We found that Cre was specifically and robustly expressed in the cardiomyocytes at embryonic and adult stages following tamoxifen induction. The knock-in allele on Tnnt2 locus does not impact cardiac function. These results suggest that this new Tnnt2MerCreMer/+ mouse could be applied towards the temporal genetic deletion of genes of interests in cardiomyocytes with Cre-LoxP technology. The Tnnt2MerCreMer/+ mouse model also provides a useful tool to trace myocardial lineage during development and repair after cardiac injury. PMID:26010701

  14. 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.

  15. 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

  16. 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.

  17. Cleavage of Mer tyrosine kinase (MerTK) from the cell surface contributes to the regulation of retinal phagocytosis.

    PubMed

    Law, Ah-Lai; Parinot, Célia; Chatagnon, Jonathan; Gravez, Basile; Sahel, José-Alain; Bhattacharya, Shomi S; Nandrot, Emeline F

    2015-02-20

    Phagocytosis of apoptotic cells by macrophages and spent photoreceptor outer segments (POS) by retinal pigment epithelial (RPE) cells requires several proteins, including MerTK receptors and associated Gas6 and protein S ligands. In the retina, POS phagocytosis is rhythmic, and MerTK is activated promptly after light onset via the αvβ5 integrin receptor and its ligand MFG-E8, thus generating a phagocytic peak. The phagocytic burst is limited in time, suggesting a down-regulation mechanism that limits its duration. Our previous data showed that MerTK helps control POS binding of integrin receptors at the RPE cell surface as a negative feedback loop. Our present results show that a soluble form of MerTK (sMerTK) is released in the conditioned media of RPE-J cells during phagocytosis and in the interphotoreceptor matrix of the mouse retina during the morning phagocytic peak. In contrast to macrophages, the two cognate MerTK ligands have an opposite effect on phagocytosis and sMerTK release, whereas the integrin ligand MFG-E8 markedly increases both phagocytosis and sMerTK levels. sMerTK acts as a decoy receptor blocking the effect of both MerTK ligands. Interestingly, stimulation of sMerTK release decreases POS binding. Conversely, blocking MerTK cleavage increased mostly POS binding by RPE cells. Therefore, our data suggest that MerTK cleavage contributes to the acute regulation of RPE phagocytosis by limiting POS binding to the cell surface.

  18. Enhanced Regulatory Sequence Prediction Using Gapped k-mer Features

    PubMed Central

    Mohammad-Noori, Morteza; Beer, Michael A.

    2014-01-01

    Abstract Oligomers of length k, or k-mers, are convenient and widely used features for modeling the properties and functions of DNA and protein sequences. However, k-mers suffer from the inherent limitation that if the parameter k is increased to resolve longer features, the probability of observing any specific k-mer becomes very small, and k-mer counts approach a binary variable, with most k-mers absent and a few present once. Thus, any statistical learning approach using k-mers as features becomes susceptible to noisy training set k-mer frequencies once k becomes large. To address this problem, we introduce alternative feature sets using gapped k-mers, a new classifier, gkm-SVM, and a general method for robust estimation of k-mer frequencies. To make the method applicable to large-scale genome wide applications, we develop an efficient tree data structure for computing the kernel matrix. We show that compared to our original kmer-SVM and alternative approaches, our gkm-SVM predicts functional genomic regulatory elements and tissue specific enhancers with significantly improved accuracy, increasing the precision by up to a factor of two. We then show that gkm-SVM consistently outperforms kmer-SVM on human ENCODE ChIP-seq datasets, and further demonstrate the general utility of our method using a Naïve-Bayes classifier. Although developed for regulatory sequence analysis, these methods can be applied to any sequence classification problem. PMID:25033408

  19. 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.

  20. Middle East respiratory syndrome (MERS): a new zoonotic viral pneumonia.

    PubMed

    Cunha, Cheston B; Opal, Steven M

    2014-08-15

    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.

  1. [Small molecular agents against MERS-CoV infection].

    PubMed

    Zeng, Xiao-yun; Lu, Lu; Jiang, Shi-bo; Liu, Shu-wen

    2015-12-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has caused outbreaks of SARS-like disease with 35% case-fatality rate, mainly in the Middle East. A more severe outbreak of MERS occurred recently in the Republic of Korea, where 186 people contracted the infections, causing great concern worldwide. So far, there has been no clinically available drug for the treatment of MERS-CoV infection. The potential drugs against MERS-CoV mainly consist of monoclonal antibodies, peptides and small molecular agents. Small molecular agents have an advantage of easier synthesis, lower cost in production and relatively higher stability. There is better chance for those candidates to gain a quick development. This article reviews the progress of developing small molecular MERS-CoV agents. PMID:27169271

  2. 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.

  3. 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.

  4. 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.

  5. 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 ...

  6. 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

  7. 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

  8. 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.

  9. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. [Development of peptidic MERS-CoV entry inhibitors].

    PubMed

    Xia, Shuai; Wang, Qian; Liu, Shu-wen; Lu, Lu; Jiang, Shi-bo

    2015-12-01

    In 2012, a new SARS-like coronavirus emerged in the Middle East, namely the Middle East respiratory syndrome coronavirus (MERS-CoV). It has caused outbreaks with high mortality. During infection of target cell, MERS-CoV S protein S1 subunit binds to the cellular receptor (DPP4), and its S2 subunit HR1 and HR2 regions intact with each other to form a stable six-helix bundle to mediate the fusion between virus and target cell membranes. Hence, blocking the process of six-helix bundle formation can effectively inhibit MERS-CoV entry into the target cells. This review focuses on the recent advance in the development of peptidic entry inhibitors targeting the MERS-CoV S2 subunit. PMID:27169270

  12. 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

  13. 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.

  14. Tubby regulates microglial phagocytosis through MerTK.

    PubMed

    Caberoy, Nora B; Alvarado, Gabriela; Li, Wei

    2012-11-15

    Immunologically-silent microglial phagocytosis of apoptotic cells and cellular debris is critical for CNS homeostasis and innate immune balance. The beneficial and detrimental effects of microglial phagocytosis on neurons remain controversial. Phagocytosis ligands are the key to selecting extracellular cargos, initiating the engulfment process, defining phagocyte functional roles and regulating phagocyte activities with therapeutic potentials. Here we characterized tubby as a new ligand to regulate microglial phagocytosis through MerTK receptor, which is well known for its immunosuppressive signaling. Tubby at 0.1nM significantly induced microglial phagocytosis of apoptotic cells with a maximal activity at 10nM. Tubby activated MerTK with receptor autophosphorylation in a similar dose range. Excessive soluble MerTK extracellular domain blocked tubby-mediated microglial phagocytosis of plasma membrane vesicles as cellular debris. Immunocytochemistry revealed that the ingested cargos were co-localized with MerTK-dependent non-muscle myosin II, whose rearrangement is necessary for cargo engulfment. Phagosome biomarker Rab7 was colocalized with cargos, suggesting that internalized cargos were targeted to phagocytic pathway. Tubby stimulated phagocytosis by neonatal and aged microglia with similar activities, but not by MerTK(-/-) microglia. These results suggest that tubby is a ligand to facilitate microglial phagocytosis through MerTK for the maintenance of CNS homeostasis.

  15. Electrotransformation of Thiobacillus ferrooxidans with plasmids containing a mer determinant.

    PubMed Central

    Kusano, T; Sugawara, K; Inoue, C; Takeshima, T; Numata, M; Shiratori, T

    1992-01-01

    The mer operon from a strain of Thiobacillus ferrooxidans (C. Inoue, K. Sugawara, and T. Kusano, Mol. Microbiol. 5:2707-2718, 1991) consists of the regulatory gene merR and an operator-promoter region followed by merC and merA structural genes and differs from other known gram-negative mer operons. We have constructed four potential shuttle plasmids composed of a T. ferrooxidans-borne cryptic plasmid, a pUC18 plasmid, and the above-mentioned mer determinant as a selectable marker. Mercury ion-sensitive T. ferrooxidans strains were electroporated with constructed plasmids, and one strain, Y4-3 (of 30 independent strains tested), was found to have a transformation efficiency of 120 to 200 mercury-resistant colonies per microgram of plasmid DNA. This recipient strain was confirmed to be T. ferrooxidans by physiological, morphological, and chemotaxonomical data. The transformants carried a plasmid with no physical rearrangements through 25 passages under no selective pressure. Cell extracts showed mercury ion-dependent NADPH oxidation activity. Images PMID:1400213

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Current advancements and potential strategies in the development of MERS-CoV vaccines

    PubMed Central

    Zhang, Naru; Jiang, Shibo; Du, Lanying

    2014-01-01

    Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future. PMID:24766432

  2. 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

  3. 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

  4. 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

  5. Synthesis and degradation of the mRNA of the Tn21 mer operon.

    PubMed

    Gambill, B D; Summers, A O

    1992-05-20

    The mercury resistance locus encoded by Tn21 on the monocopy IncFII plasmid R100 (merTn21) consists of a metal-responsive activator/repressor, merR, which controls initiation of a polycistronic message that includes genes for the uptake (merTPC) and reduction (merA) of Hg2+ and merD, which may also play a minor regulatory role. Comparison of the relative abundance of the 5' and 3' ends of the merTPCAD transcript revealed a strong transcriptional gradient in the operon, consistent with previous observations of lower relative abundance of the more promoter-distal gene products. In vivo mRNA degradation rates varied only slightly for the different genes: however, the rates of mRNA synthesis varied considerably from the beginning to the end of the operon. Specifically, mRNA corresponding to the promoter-proximal genes, merTPC, achieved a maximum in vivo synthesis rate between 60 and 120 seconds after induction; this rate was maintained for approximately ten minutes. In contrast, the synthesis rates of mRNA corresponding to the promoter-distal genes merA and merD, were initially fivefold lower than the rates of the promoter-proximal genes for the first five minutes after induction, and then rose gradually to approximately 50% of the merTPC synthesis rates. These data suggested that early after induction only 20% of the transcripts initiating at merT proceed beyond merC. At later times after induction approximately 50% of the transcripts proceed beyond merC. Nuclease end mapping did not reveal any discrete termination events in the merPCA region, thus, premature termination may occur at many sites.

  6. 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.

  7. These are not the k-mers you are looking for: efficient online k-mer counting using a probabilistic data structure.

    PubMed

    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.

  8. 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.

  9. 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

  10. 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+}.

  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. 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

  13. 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

  14. 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

  15. K-mer natural vector and its application to the phylogenetic analysis of genetic sequences

    PubMed Central

    Wen, Jia; Chan, Raymond H.; Yau, Shek-Chung; He, Rong L.; Yau, Stephen S. T.

    2014-01-01

    Based on the well-known k-mer model, we propose a k-mer natural vector model for representing a genetic sequence based on the numbers and distributions of k-mers in the sequence. We show that there exists a one-to-one correspondence between a genetic sequence and its associated k-mer natural vector. The k-mer natural vector method can be easily and quickly used to perform phylogenetic analysis of genetic sequences without requiring evolutionary models or human intervention. Whole or partial genomes can be handled more effective with our proposed method. It is applied to the phylogenetic analysis of genetic sequences, and the obtaining results fully demonstrate that the k-mer natural vector method is a very powerful tool for analysing and annotating genetic sequences and determining evolutionary relationships both in terms of accuracy and efficiency. PMID:24858075

  16. [Infections with the MERS coronavirus--for the present no threat to Europe].

    PubMed

    Stock, Ingo

    2015-12-01

    In Saudi Arabia, a novel coronavirus named Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated in 2012 from patients with severe respiratory symptoms. Up to now, more than 1600 MERS cases have been registered mainly in the Arabian Peninsula. MERS is usually accompanied with fever, cough, and shortness of breath. In many cases, pneumonia is observed. However, clinical features of MERS range from mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. To date, about one in three people died as a result of MERS. In Europe, MERS cases have only been registered in isolated travelers entering from the Middle East.

  17. 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

  18. 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

  19. Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?

    PubMed Central

    Chung, Jasmine Shimin; Ling, Moi Lin; Seto, Wing Hong; Ang, Brenda Sze Peng; Tambyah, Paul Anantharajah

    2014-01-01

    Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV. PMID:25017402

  20. 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

  1. Mercuric reductase genes (merA) and mercury resistance plasmids in High Arctic snow, freshwater and sea-ice brine.

    PubMed

    Møller, Annette K; Barkay, Tamar; Hansen, Martin A; Norman, Anders; Hansen, Lars H; Sørensen, Søren J; Boyd, Eric S; Kroer, Niels

    2014-01-01

    Bacterial reduction in Hg(2+) to Hg(0) , mediated by the mercuric reductase (MerA), is important in the biogeochemical cycling of Hg in temperate environments. Little is known about the occurrence and diversity of merA in the Arctic. Seven merA determinants were identified among bacterial isolates from High Arctic snow, freshwater and sea-ice brine. Three determinants in Bacteriodetes, Firmicutes and Actinobacteria showed < 92% (amino acid) sequence similarity to known merA, while one merA homologue in Alphaproteobacteria and 3 homologues from Betaproteobacteria and Gammaproteobacteria were > 99% similar to known merA's. Phylogenetic analysis showed the Bacteroidetes merA to be part of an early lineage in the mer phylogeny, whereas the Betaproteobacteria and Gammaproteobacteria merA appeared to have evolved recently. Several isolates, in which merA was not detected, were able to reduce Hg(2+) , suggesting presence of unidentified merA genes. About 25% of the isolates contained plasmids, two of which encoded mer operons. One plasmid was a broad host-range IncP-α plasmid. No known incompatibility group could be assigned to the others. The presence of conjugative plasmids, and an incongruent distribution of merA within the taxonomic groups, suggests horizontal transfer of merA as a likely mechanism for High Arctic microbial communities to adapt to changing mercury concentration.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Structural insights into the inhibited states of the Mer receptor tyrosine kinase

    PubMed Central

    Huang, Xudong; Finerty, Patrick; Walker, John R.; Butler-Cole, Christine; Vedadi, Masoud; Schapira, Matthieu; Parker, Sirlester A.; Turk, Benjamin E.; Thompson, Debra A.; Dhe-Paganon, Sirano

    2009-01-01

    The mammalian ortholog of the retroviral oncogene v-Eyk, and a receptor tyrosine kinase upstream of antiapoptotic and transforming signals, Mer (MerTK) is a mediator of the phagocytic process, being involved in retinal and immune cell clearance and platelet aggregation. Mer knockout mice are viable and are protected from epinephrine-induced pulmonary thromboembolism and ferric chloride-induced thrombosis. Mer overexpression, on the other hand, is associated with numerous carcinomas. Although Mer adaptor proteins and signaling pathways have been identified, it remains unclear how Mer initiates phagocytosis. When bound to its nucleotide cofactor, the high-resolution structure of Mer shows an autoinhibited αC-Glu-out conformation with insertion of an activation loop residue into the active site. Mer complexed with compound-52 (C52: 2-(2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine), a ligand identified from a focused library, retains its DFG-Asp-in and αC-Glu-out conformation, but acquires other conformational changes. The αC helix and DFGL region is closer to the hinge region and the ethanolamine moiety of C52 binds in the groove formed between Leu593 and Val601 of the P-loop, causing a compression of the active site pocket. These conformational states reveal the mechanisms of autoinhibition, the pathophysiological basis of disease-causing mutations, and a platform for the development of chemical probes. PMID:19028587

  8. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis.

    PubMed

    Caberoy, Nora B; Zhou, Yixiong; Li, Wei

    2010-12-01

    Tubby and tubby-like protein 1 (Tulp1) are newly identified phagocytosis ligands to facilitate retinal pigment epithelium (RPE) and macrophage phagocytosis. Both proteins without classical signal peptide have been demonstrated with unconventional secretion. Here, we characterized them as novel MerTK ligands to facilitate phagocytosis. Tulp1 interacts with Tyro3, Axl and MerTK of the TAM receptor tyrosine kinase subfamily, whereas tubby binds only to MerTK. Excessive soluble MerTK extracellular domain blocked tubby- or Tulp1-mediated phagocytosis. Both ligands induced MerTK activation with receptor phosphorylation and signalling cascade, including non-muscle myosin II redistribution and co-localization with phagosomes. Tubby and Tulp1 are bridging molecules with their N-terminal region as MerTK-binding domain and C-terminal region as phagocytosis prey-binding domain (PPBD). Five minimal phagocytic determinants (MPDs) of K/R(X)(1-2)KKK in Tulp1 N-terminus were defined as essential motifs for MerTK binding, receptor phosphorylation and phagocytosis. PPBD was mapped to the highly conserved 54 amino acids at the C-terminal end of tubby and Tulp1. These data suggest that tubby and Tulp1 are novel bridging molecules to facilitate phagocytosis through MerTK.

  9. 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

  10. 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

  11. 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

  12. Lack of MERS Coronavirus Neutralizing Antibodies in Humans, Eastern Province, Saudi Arabia

    PubMed Central

    Gierer, Stefanie; Hofmann-Winkler, Heike; Albuali, Waleed H.; Bertram, Stephanie; Al-Rubaish, Abdullah M.; Yousef, Abdullah A.; Al-Nafaie, Awatif N.; Al-Ali, Amein K.; Obeid, Obeid E.; Alkharsah, Khaled R.

    2013-01-01

    We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province. PMID:24274664

  13. MERS-CoV spike protein: Targets for vaccines and therapeutics.

    PubMed

    Wang, Qihui; Wong, Gary; Lu, Guangwen; Yan, Jinghua; Gao, George F

    2016-09-01

    The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable. The MERS-CoV spike (S) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infection. In this review, we highlight the importance of the S protein in the MERS-CoV life cycle, summarize recent advances in the development of vaccines and therapeutics based on the S protein, and discuss strategies that can be explored to develop new medical countermeasures against MERS-CoV. PMID:27468951

  14. 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.

  15. Inferences of Strength of Soil Deposits Along MER Rover Traverses

    NASA Astrophysics Data System (ADS)

    Richter, L. O.

    2005-12-01

    As the two Mars Exploration Rovers 'Spirit' and 'Opportunity' traverse terrains within Gusev crater and at Meridiani Planum, respectively, they leave behind wheel tracks that are routinely imaged by the different sets of cameras as part of the MER Athena instrument suite. Stereo observations of these tracks reveal wheel rut depths which are diagnostic of the strength of the soil-like deposits crossed by the vehicles. This contribution will discuss results of systematic analyses of MER-A and -B wheel sinkage measurements with regard to solutions for soil bearing strength, cohesion, and friction angle, occurring in the context of a suite of physical properties studies that are part of the Athena science investigation. Sinkage data are analyzed with wheel-soil theory calibrated to the shape of the MER wheel while accounting for wheel slip and by consulting comparisons with terrestrial soils. Results are applicable to the top ~20 to 30 cm of the soil deposits 'sampled' by normal stresses incurred from the wheels. The large number of wheel track observations per distance travelled enables investigations of variations of soil physical properties as a function of spatial scale, type of surface feature encountered, and local topography. Exploiting relationships between soil strength and degree of soil consolidation known from lunar regolith and dry terrestrial soils allows one to relate inferred soil strengths to bulk density which in turn is related to dielectric properties and to fine-component thermal inertia, both of which have been constrained for the two MER landing sites by remote sensing with comparatively coarse spatial resolution. In the context of the Athena science investigation, physical properties studies contribute to an overall understanding of the geology at the landing sites as they i) allow comparisons to be made between physical and compositional properties, ii) support attempts to correlate materials with geologic units, iii) help identify

  16. 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.

  17. Dust Accumulation and Cleaning of the MER Opportunity Solar Array

    NASA Astrophysics Data System (ADS)

    Herman, J.

    2015-12-01

    The solar array of the NASA Mars Exploration Rover (MER) Opportunity was expected to accumulate a sufficient quantity of dust after ninety Martian days (sols) such that it could no longer provide enough energy to guarantee continued surface operations. Instead, due in part to low dust accumulation rates and numerous dust cleaning events, Opportunity continues to operate on the Martian surface for over 4000 sols (over six Mars years). During this time period, the rover experienced six Martian winters and several dust storms. Because the sources of solar energy loss are known, the solar array energy output offers a method to scientifically estimate the loading and aeolian removal of dust from the solar array each sol. We will discuss the accumulation of dust on the solar panels as a proxy for dust movement at Meridiani Planum over the course of the entire mission to date.

  18. Dust Accumulation and Cleaning of the MER Spirit Solar Array

    NASA Astrophysics Data System (ADS)

    Herman, J. A.; Lemmon, M. T.; Johnson, J. R.; Cantor, B. A.; Stella, P. M.; Chin, K. B.; Wood, E. G.

    2012-12-01

    The solar array of the NASA Mars Exploration Rover (MER) Spirit was expected to accumulate so much dust after ninety Martian days (sols) that it could no longer provide enough energy to guarantee continued surface operations. Instead, due in part to low dust accumulation rates and numerous dust cleaning events, Spirit carried out surface operations for over 2200 sols (over three Mars years). During this time period, the rover experienced four Martian winters and several dust storms. Because the sources of solar energy loss are known, the solar array energy output offers a tool to quantitatively estimate the loading and aeolian removal of dust from the solar array each sol. We will discuss the accumulation of dust on the solar panels as a proxy for dust movement at Gusev Crater over the course of the entire mission.

  19. Dust Accumulation and Cleaning of the MER Solar Arrays

    NASA Astrophysics Data System (ADS)

    Herman, J. A.; Lemmon, M. T.; Stella, P.; Chin, K. B.; Wood, E. G.

    2010-12-01

    The solar arrays of the two NASA Mars Exploration Rovers (MER), Spirit and Opportunity, were expected to accumulate so much dust after 90 Martian days (sols) that they could no longer provide enough energy to guarantee continued surface operations. Instead, due in part to low dust accumulation rates and numerous dust cleaning events, they have carried out surface operations for over 2200 sols each. During this time period, the rovers experienced four Martian winters and several dust storms. Because the sources of solar energy loss are known, the solar array energy output offers a tool to scientifically estimate the loading and aeolian removal of dust from the solar arrays each sol. We will discuss the accumulation of dust on the solar panels as a proxy for dust movement on the Martian surface over the last 6 years.

  20. 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.

  1. Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: a case report.

    PubMed

    Shalhoub, Sarah; AlZahrani, Abdulwahab; Simhairi, Raed; Mushtaq, Adnan

    2015-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS CoV) may cause severe pneumonia with significant morbidity and mortality, particularly in patients with multiple comorbid condition. MERS CoV pneumonia has not been previously reported in patients with Human Immunodeficiency Virus (HIV). Herein, we report a case of MERS CoV pneumonia with a successful outcome in a patient recently diagnosed with HIV.

  2. Spacecraft Observations of Atmospheric Temperature and Aerosol Optical Depth Near the Time of the MER Landings

    NASA Astrophysics Data System (ADS)

    Smith, M. D.

    2005-05-01

    Continued atmospheric monitoring by the Mars Global Surveyor TES and Mars Odyssey THEMIS instruments provided daily maps of the regional to global scale variation of atmospheric temperature and aerosol optical depth before, during, and after the time of the two Mars Exploration Rover (MER) landings in January 2005. After landing, the MER Mini-TES instrument provided additional complementary information about the late-summer atmospheric state at the Gusev Crater and Meridiani Planum landing sites. Orbital observations taken before the MER landings documented the initiation, growth, and decay of a large regional dust storm in mid-December 2004, just weeks before the MER Spirit landing. This dust storm caused an increase in atmospheric temperature above nominal seasonal values, and left relatively dusty conditions for the rovers after landing. Atmospheric entry parameters such as the height at which to open the parachute were adjusted considering the daily TES updates in the days before both MER landings. Here we present observations of atmospheric temperatures and aerosol optical depth by TES and THEMIS in the time period near the MER landings. We compare the TES and THEMIS observations against the values predicted from climatology and the observations taken after landing by the MER Mini-TES.

  3. The receptor binding domain of MERS-CoV: the dawn of vaccine and treatment development.

    PubMed

    Zhou, Nan; Zhang, Yun; Zhang, Jin-Chun; Feng, Ling; Bao, Jin-Ku

    2014-03-01

    The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is becoming another "SARS-like" threat to the world. It has an extremely high death rate (∼50%) as there is no vaccine or efficient therapeutics. The identification of the structures of both the MERS-CoV receptor binding domain (RBD) and its complex with dipeptidyl peptidase 4 (DPP4), raises the hope of alleviating this currently severe situation. In this review, we examined the molecular basis of the RBD-receptor interaction to outline why/how could we use MERS-CoV RBD to develop vaccines and antiviral drugs.

  4. NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV).

    PubMed

    Huang, Yi-Ping; Cho, Chao-Cheng; Chang, Chi-Fon; Hsu, Chun-Hua

    2016-10-01

    The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. Intense research has shown that macro domains bind ADP-ribose and other derivatives, but it still remains intangible about their exact function. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?

    PubMed

    Omrani, A S; Shalhoub, S

    2015-11-01

    The Middle East Respiratory Coronavirus (MERS-CoV) was first isolated from a patient who died with severe pneumonia in June 2012. As of 19 June 2015, a total of 1,338 MERS-CoV infections have been notified to the World Health Organization (WHO). Clinical illness associated with MERS-CoV ranges from mild upper respiratory symptoms to rapidly progressive pneumonia and multi-organ failure. A significant proportion of patients present with non-respiratory symptoms such as headache, myalgia, vomiting and diarrhoea. A few potential therapeutic agents have been identified but none have been conclusively shown to be clinically effective. Human to human transmission is well documented, but the epidemic potential of MERS-CoV remains limited at present. Healthcare-associated clusters of MERS-CoV have been responsible for the majority of reported cases. The largest outbreaks have been driven by delayed diagnosis, overcrowding and poor infection control practices. However, chains of MERS-CoV transmission can be readily interrupted with implementation of appropriate control measures. As with any emerging infectious disease, guidelines for MERS-CoV case identification and surveillance evolved as new data became available. Sound clinical judgment is required to identify unusual presentations and trigger appropriate control precautions. Evidence from multiple sources implicates dromedary camels as natural hosts of MERS-CoV. Camel to human transmission has been demonstrated, but the exact mechanism of infection remains uncertain. The ubiquitously available social media have facilitated communication and networking amongst healthcare professionals and eventually proved to be important channels for presenting the public with factual material, timely updates and relevant advice. PMID:26452615

  13. Development of Animal Models Against Emerging Coronaviruses: From SARS to MERS coronavirus

    PubMed Central

    Sutton, Troy C; Subbarao, Kanta

    2016-01-01

    Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV. PMID:25791336

  14. 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

  15. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013.

    PubMed

    Meyer, Benjamin; Müller, Marcel A; Corman, Victor M; Reusken, Chantal B E M; Ritz, Daniel; Godeke, Gert-Jan; Lattwein, Erik; Kallies, Stephan; Siemens, Artem; van Beek, Janko; Drexler, Jan F; Muth, Doreen; Bosch, Berend-Jan; Wernery, Ulrich; Koopmans, Marion P G; Wernery, Renate; Drosten, Christian

    2014-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein-specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV-neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.

  16. 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

  17. 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

  18. DNA sequence analysis by hybridization with oligonucleotide microchips : MALDI mass spectrometry identification of 5mers contiguously stacked to microchip oligonucleotides.

    SciTech Connect

    Stomakhin, A. A.; Vasiliskov, V. A.; Timofeev, E.; Schulga, D.; Cotter, R. J.; Mirzabekov, A. D.; Biochip Technology Center; Engelhardt Inst. of Molecular Biology; Moscow Inst. of Physics and Technology; Middle Atlantic Mass Spectrometry Lab.; Johns Hopkins Univ. School of Medicine

    2000-01-01

    Matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has been applied to increase the informational output from DNA sequence analysis. It has been used to analyze DNA by hybridization with microarrays of gel-immobilized oligonucleotides extended with stacked 5mers. In model experiments, a 28 nt long DNA fragment was hybridized with 10 immobilized, overlapping 8mers. Then, in a second round of hybridization DNA-8mer duplexes were hybridized with a mixture of 10 5mers. The stability of the 5mer complex with DNA was increased to raise the melting temperature of the duplex by 10-15{sup o}C as a result of stacking interaction with 8mers. Contiguous 13 bp duplexes containing an internal break were formed. MALDI MS identified one or, in some cases, two 5mers contiguously stacked to each DNA-8mer duplex formed on the microchip. Incorporating a mass label into 5mers optimized MALDI MS monitoring. This procedure enabled us to reconstitute the sequence of a model DNA fragment and identify polymorphic nucleotides. The application of MALDI MS identification of contiguously stacked 5mers to increase the length of DNA for sequence analysis is discussed.

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

    NASA Astrophysics Data System (ADS)

    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 dc is observed. In the zero-defect lattices, the jamming concentration pj (RRSA model) and the density of single clusters ps (RSC model) decrease with increasing length k -mers and with a decrease in the order parameter. For the RRSA model, the value of dc decreases for short k -mers (k <16 ) as the value of s increases. For k =16 and 32, the value of dc 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 ps at the critical concentration of defects dc 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 ps tends towards zero in the limits of the very long k -mers, k →∞ , and very small critical concentrations dc→0 . In this case, the introduction of defects results in a suppression of k -mer stacking and in the formation of empty or loose

  20. 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

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Efficacy of a Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in acute myeloid leukemia

    PubMed Central

    Lee-Sherick, Alisa B.; Zhang, Weihe; Menachof, Kelly K.; Hill, Amanda A.; Rinella, Sean; Kirkpatrick, Gregory; Page, Lauren S.; Stashko, Michael A.; Jordan, Craig T.; Wei, Qi; Liu, Jing; Zhang, Dehui; DeRyckere, Deborah; Wang, Xiaodong; Frye, Stephen; Earp, H. Shelton; Graham, Douglas K.

    2015-01-01

    Mer and Flt3 receptor tyrosine kinases have been implicated as therapeutic targets in acute myeloid leukemia (AML). In this manuscript we describe UNC1666, a novel ATP-competitive small molecule tyrosine kinase inhibitor, which potently diminishes Mer and Flt3 phosphorylation in AML. Treatment with UNC1666 mediated biochemical and functional effects in AML cell lines expressing Mer or Flt3 internal tandem duplication (ITD), including decreased phosphorylation of Mer, Flt3 and downstream effectors Stat, Akt and Erk, induction of apoptosis in up to 98% of cells, and reduction of colony formation by greater than 90%, compared to treatment with vehicle. These effects were dose-dependent, with inhibition of downstream signaling and functional effects correlating with the degree of Mer or Flt3 kinase inhibition. Treatment of primary AML patient samples expressing Mer and/or Flt3-ITD with UNC1666 also inhibited Mer and Flt3 intracellular signaling, induced apoptosis, and inhibited colony formation. In summary, UNC1666 is a novel potent small molecule tyrosine kinase inhibitor that decreases oncogenic signaling and myeloblast survival, thereby validating dual Mer/Flt3 inhibition as an attractive treatment strategy for AML. PMID:25762638

  16. Inhibition of Mer and Axl receptor tyrosine kinases leads to increased apoptosis and improved chemosensitivity in human neuroblastoma.

    PubMed

    Li, Yixin; Wang, Xiqian; Bi, Shaojie; Zhao, Kun; Yu, Chao

    2015-02-13

    Ectopic expression of Mer and Axl receptor tyrosine kinases (RTKs) are frequently found in various cancers as known to promote oncogenesis by activating antiapoptotic signaling pathways. However, the roles of these receptors in neuroblastoma remain unclear. We found Mer and Axl was co-expressed in neuroblastoma patient samples and cell lines. Ligand-dependent Mer or Axl activation led to an increase in phosphorylated ERK1/2, AKT and FAK indicating roles for these RTKs in multiple oncogenic processes. Furthermore, Mer and Axl knockdown led to apoptosis and inhibition of migration as well as a significant increase in chemosensitivity in response to cisplatin and vincristine treatment. Taken together, our results demonstrated that inhibition of Mer and Axl improved apoptotic response and chemosensitivity in neuroblastoma, providing new insights into development of novel therapeutic strategies by targeting these oncogenes.

  17. Structure and conformational dynamics of the metalloregulator MerR upon binding of Hg(II).

    PubMed

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

    2010-05-14

    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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Simulating a MER Landing Site Remote Sensing Data Set for the 2002 FIDO Field Test

    NASA Astrophysics Data System (ADS)

    Andres, P. M.; Anderson, R. C.; Bryant, N. A.; Capraro, K. S.; de Jong, E. M.; Haldemann, A. F.; Kiefer, D. E.; Levoe, S. R.; Logan, T. L.; Stein, T.

    2002-12-01

    To support the Field Integrated Design and Operations (FIDO) rover field test for Mars Exploration Rover (MER) science team training, we assembled a portfolio of modified terrestrial remote-sensing data to imitate the datasets available for MER landing sites. The MER landing sites data we synthesized were:\\(i) Viking MDIM base images at around 200 m/pixel, \\(ii) interpolated 1/64th degree Mars Global Surveyor (MGS) Mars Orbital Laser Altimeter (MOLA) topography, \\(iii) MOLA topographic profiles, \\(iv) some number of MGS Mars Orbiter Camera (MOC) high resolution strips, \\(v) Mars Odyssey Thermal Emission Imaging Spectrometer (THEMIS) visible (VIS) and short-wave infrared (SWIR) reflectance images, and \\(vi) THEMIS thermal IR (TIR) emissivity images. \\Terrestrial datasets selected and modified were (respectively):\\(i) Landsat TM composite images 90 m/pixel degraded to 180 m/pixel, \\(ii) USGS 90 m/pixel DEM degraded to 450 m/pixel, \\(iii) the same USGS 90 m/pixel DEM was individually sampled to generate 100 m shot size MOLA profiles, \\(iv) USGS Digital Orthoquad 1 m/pixel aerial photographs, mosaiced, cropped and re-sampled to 1.5, 3, and 7 m/pixel, \\(v) ASTER VIS and SWIR Level 2 reflectance, and \\(vi) ASTER TIR emissivity images.\\The MER Athena science team was able to successfully assess and evaluate the scientific potential of their test "landing ellipse" using these data, suggesting that the team will be capable of similar interpretive extrapolation on Mars.

  4. 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

  5. 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.

  6. 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

  7. Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow

    PubMed Central

    Jung, Younghun; Decker, Ann M.; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A.; Yumoto, Kenji; Cackowski, Frank C.; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M.; Taichman, Russell S.

    2016-01-01

    GAS6 and its receptors (Tryo 3, Axl, Mer or “TAM”) are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment. We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. setting. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133–/CD44–) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo. Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease. PMID:27028863

  8. Probabilistic differential diagnosis of Middle East respiratory syndrome (MERS) using the time from immigration to illness onset among imported cases.

    PubMed

    Ejima, Keisuke; Aihara, Kazuyuki; Nishiura, Hiroshi

    2014-04-01

    Middle East respiratory syndrome (MERS) has spread worldwide since 2012. As the clinical symptoms of MERS tend to be non-specific, the incubation period has been shown to complement differential diagnosis, especially to rule out influenza. However, because an infection event is seldom directly observable, the present study aims to construct a diagnostic model that predicts the probability of MERS diagnosis given the time from immigration to illness onset among imported cases which are suspected of MERS. Addressing censoring by considering the transmission dynamics in an exporting country, we demonstrate that the illness onset within 2 days from immigration is suggestive of influenza. Two exceptions to suspect MERS even for those with illness onset within 2 days since immigration are (i) when we observe substantial community transmissions of MERS and (ii) when the cases are at high risk of MERS (e.g. cases with close contact in hospital or household). It is vital to collect the information of the incubation period upon emergence of a novel infectious disease, and moreover, in our model, the fundamental transmission dynamics including the initial growth rate has to be explored to differentiate the disease diagnoses with non-specific symptoms.

  9. A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein

    PubMed Central

    Li, Yan; Wan, Yuhua; Liu, Peipei; Zhao, Jincun; Lu, Guangwen; Qi, Jianxun; Wang, Qihui; Lu, Xuancheng; Wu, Ying; Liu, Wenjun; Zhang, Buchang; Yuen, Kwok-Yung; Perlman, Stanley; Gao, George F; Yan, Jinghua

    2015-01-01

    The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings. PMID:26391698

  10. 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.

  11. 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.

  12. 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

  13. Mechanism of Hg-C protonolysis in the organomercurial lyase MerB.

    PubMed

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

    2009-09-23

    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.

  14. 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

  15. 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...

  16. Equation of state for two-dimensional fluids with hard cyclic n-mer molecules

    NASA Astrophysics Data System (ADS)

    Maeso, M. J.; Solana, J. R.

    1995-12-01

    The procedure previously developed to obtain the equation of state of two-dimensional fluids of hard linear molecules is modified for application to cyclic molecules. The resulting equation of state of two-dimensional hard cyclic n-mer fluids is related to the equation of state of the hard disc fluid and reproduces simulation data within their uncertainty for all the molecular geometries considered.

  17. 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.

  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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa.

    PubMed

    Wang, Dan; Huang, Shanqing; Liu, Pingying; Liu, Xichun; He, Yafeng; Chen, Weizhong; Hu, Qingyuan; Wei, Tianbiao; Gan, Jianhua; Ma, Jing; Chen, Hao

    2016-01-01

    The metalloprotein MerR is a mercury(II)-dependent transcriptional repressor-activator that responds to mercury(II) with extraordinary sensitivity and selectivity. It's widely distributed in both Gram-negative and Gram-positive bacteria but with barely detectable sequence identities between the two sources. To provide structural basis for the considerable biochemical and biophysical experiments previously performed on Tn501 and Tn21 MerR from Gram-negative bacteria, we analyzed the crystal structure of mercury(II)-bound Tn501 MerR. The structure in the metal-binding domain provides Tn501 MerR with a high affinity for mercury(II) and the ability to distinguish mercury(II) from other metals with its unique planar trigonal coordination geometry, which is adopted by both Gram-negative and Gram-positive bacteria. The mercury(II) coordination state in the C-terminal metal-binding domain is transmitted through the allosteric network across the dimer interface to the N-terminal DNA-binding domain. Together with the previous mutagenesis analyses, the present data indicate that the residues in the allosteric pathway have a central role in maintaining the functions of Tn501 MerR. In addition, the complex structure exhibits significant differences in tertiary and quaternary structural arrangements compared to those of Bacillus MerR from Gram-positive bacteria, which probably enable them to function with specific promoter DNA with different spacers between -35 and -10 elements. PMID:27641146

  10. 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.

  11. Improvement of an enzyme-linked immunosorbent assay for equine herpesvirus type 4 by using a synthetic-peptide 24-mer repeat sequence of glycoprotein G as an antigen.

    PubMed

    Bannai, Hiroshi; Nemoto, Manabu; Tsujimura, Koji; Yamanaka, Takashi; Maeda, Ken; Kondo, Takashi

    2016-02-01

    To increase the sensitivity of an enzyme-linked immunosorbent assay (ELISA) for equine herpesvirus type 4 (EHV-4) that uses a 12-mer peptide of glycoprotein G (gG4-12-mer: MKNNPIYSEGSL) [4], we used a longer peptide consisting of a 24-mer repeat sequence (gG4-24-mer: MKNNPIYSEGSLMLNVQHDDSIHT) as an antigen. Sera of horses experimentally infected with EHV-4 reacted much more strongly to the gG4-24-mer peptide than to the gG4-12-mer peptide. We used peptide ELISAs to test paired sera from horses naturally infected with EHV-4 (n=40). gG4-24-mer ELISA detected 37 positive samples (92.5%), whereas gG4-12-mer ELISA detected only 28 (70.0%). gG4-24-mer ELISA was much more sensitive than gG4-12-mer ELISA.

  12. Improvement of an enzyme-linked immunosorbent assay for equine herpesvirus type 4 by using a synthetic-peptide 24-mer repeat sequence of glycoprotein G as an antigen

    PubMed Central

    BANNAI, Hiroshi; NEMOTO, Manabu; TSUJIMURA, Koji; YAMANAKA, Takashi; MAEDA, Ken; KONDO, Takashi

    2015-01-01

    To increase the sensitivity of an enzyme-linked immunosorbent assay (ELISA) for equine herpesvirus type 4 (EHV-4) that uses a 12-mer peptide of glycoprotein G (gG4-12-mer: MKNNPIYSEGSL) [4], we used a longer peptide consisting of a 24-mer repeat sequence (gG4-24-mer: MKNNPIYSEGSLMLNVQHDDSIHT) as an antigen. Sera of horses experimentally infected with EHV-4 reacted much more strongly to the gG4-24-mer peptide than to the gG4-12-mer peptide. We used peptide ELISAs to test paired sera from horses naturally infected with EHV-4 (n=40). gG4-24-mer ELISA detected 37 positive samples (92.5%), whereas gG4-12-mer ELISA detected only 28 (70.0%). gG4-24-mer ELISA was much more sensitive than gG4-12-mer ELISA. PMID:26424485

  13. 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

  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.

  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. 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

  17. 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

  18. [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

  19. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease.

    PubMed

    Johnson, Reed F; Via, Laura E; Kumar, Mia R; Cornish, Joseph P; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L; Mazur, Steven; Allan, Cindy; Holbrook, Michael R; Solomon, Jeffrey; Johnson, Joshua C; Pickel, James; Hensley, Lisa E; Jahrling, Peter B

    2015-11-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication.

  20. A novel nickel responsive MerR-like regulator, NimR, from Haemophilus influenzae.

    PubMed

    Kidd, Stephen P; Djoko, Karrera Y; Ng, JiaQi; Argente, M Pilar; Jennings, Michael P; McEwan, Alastair G

    2011-10-01

    We have identified a novel regulator from the MerR family of transcription factors in the bacterial pathogen Haemophilus influenzae (HI1623; nickel-associated merR-like Regulator--NimR). NimR regulates the expression of a Ni(2+) uptake transporter (NikKLMQO). The promoters for nimR and the nik operon are divergent and overlapping and NimR binds at a site between the promoter elements for nikKLMQO. Expression of this operon requires NimR and depends on Ni(2+). Growth rates of the H. influenzae nimR and nikQ mutants were reduced in chemically defined media compared to the wild type and the mutants were unable to grow in the presence of EDTA. The mutant strains were less tolerant of acidic pH and the wild type Rd KW20 could not tolerate low pH in the presence of fluoramide, a urease specific inhibitor, confirming that both nickel transport and urea hydrolysis are a central process in pH control. H. influenzae nimR and nikQ strains were deficient in urease activity, but this could be specifically restored by the addition of excess Ni(2+). NimR did not directly regulate the expression of urease genes but the activity of urease requires both nimR and nikQ. Purified NimR is a dimer that binds 1 Ni(2+)ion. NimR is the first example of a Ni-dependent regulator from the MerR family and targeting a metal ion uptake system; it is distinct from NikR the Ni-responsive regulators of the ribbon-helix-helix family. PMID:21952667

  1. 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

  2. 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling.

    PubMed

    Hsieh, Ying-Hen

    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 R 0 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. R 0 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 R 0 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 nosocomial

  3. Electrical conductivity of a monolayer produced by random sequential adsorption of linear k -mers onto a square lattice

    NASA Astrophysics Data System (ADS)

    Tarasevich, Yuri Yu.; Goltseva, Valeria A.; Laptev, Valeri V.; Lebovka, Nikolai I.

    2016-10-01

    The electrical conductivity of a monolayer produced by the random sequential adsorption (RSA) of linear k -mers (particles occupying k adjacent adsorption sites) onto a square lattice was studied by means of computer simulation. Overlapping with predeposited k -mers and detachment from the surface were forbidden. The RSA process continued until the saturation jamming limit, pj. The isotropic (equiprobable orientations of k -mers along x and y axes) and anisotropic (all k -mers aligned along the y axis) depositions for two different models—of an insulating substrate and conducting k -mers (C model) and of a conducting substrate and insulating k -mers (I model)—were examined. The Frank-Lobb algorithm was applied to calculate the electrical conductivity in both the x and y directions for different lengths (k =1 - 128) and concentrations (p =0 - pj) of the k -mers. The "intrinsic electrical conductivity" and concentration dependence of the relative electrical conductivity Σ (p ) (Σ =σ /σm for the C model and Σ =σm/σ for the I model, where σm is the electrical conductivity of substrate) in different directions were analyzed. At large values of k the Σ (p ) curves became very similar and they almost coincided at k =128 . Moreover, for both models the greater the length of the k -mers the smoother the functions Σx y(p ) ,Σx(p ) and Σy(p ) . For the more practically important C model, the other interesting findings are (i) for large values of k (k =64 ,128 ), the values of Σx y and Σy increase rapidly with the initial increase of p from 0 to 0.1; (ii) for k ≥16 , all the Σx y(p ) and Σx(p ) curves intersect with each other at the same isoconductivity points; (iii) for anisotropic deposition, the percolation concentrations are the same in the x and y directions, whereas, at the percolation point the greater the length of the k -mers the larger the anisotropy of the electrical conductivity, i.e., the ratio σy/σx (>1 ).

  4. 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 .

  5. 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

  6. 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.

  7. Coordinated expression of tyro3, axl, and mer receptors in macrophage ontogeny

    PubMed Central

    Malawista, Anna; Wang, Xiaomei; Trentalange, Mark; Allore, Heather G.; Montgomery, Ruth R.

    2016-01-01

    The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3−/−, Axl−/−, Mer−/−) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions. We have quantified changes in TAM expression during the ontogeny of human macrophages using paired samples of monocytes and macrophages to take advantage of characteristic expression within an individual. No significant differences in levels of Tyro3 were found between monocytes and macrophages (flow cytometry: p=0.652, immunoblot: p=0.231, qPCR: p=0.389). Protein levels of Axl were reduced (flow cytometry: p=0.049, immunoblot: p<0.001) when monocytes matured to macrophages. No significant differences in the levels of Axl mRNA transcripts were found (qPCR: p=0.082), however, Tyro3 and Axl were proportionate. The most striking difference was upregulation of expression of Mer with both protein and mRNA being significantly increased when monocytes developed into macrophages (flow cytometry: p<0.001, immunoblot: p<0.001, qPCR: p=0.004). A fuller characterization of TAM receptor expression in macrophage ontogeny informs our understanding of their function and potential therapeutic interventions.

  8. Exploring the GalMer database: bar properties and non-circular motions

    NASA Astrophysics Data System (ADS)

    Randriamampandry, T. H.; Deg, N.; Carignan, C.; Combes, F.; Spekkens, K.

    2016-10-01

    Context. We use Tree-SPH simulations from the GalMer database to characterize and quantify the non-circular motions induced by the presence of bar-like structures on the observed rotation curve of barred galaxies derived from empirical models of their line-of-sight velocity maps. The GalMer database consists of SPH simulations of galaxies spanning a wide range of morphological types and sizes. Aims: The aim is to compare the intrinsic velocities and bar properties from the simulations with those derived from pseudo-observations. This allows us to estimate the amount of non-circularity and to test the various methods used to derive the bar properties and rotation curves. Methods: The intrinsic velocities in the simulations are calculated from the gravitational forces whereas the observed rotation velocities are derived by applying the ROTCUR and DiskFit algorithms to well-resolved observations of intermediate-inclination, strongly barred galaxies. Results: Our results confirm that the tilted ring method implemented in ROTCUR systematically underestimates or overestimates the rotational velocities by up to 40 percent in the inner part of the galaxy when the bar is aligned with one of the symmetry axes for all the models. For the DiskFit analysis, we find that it produces unrealistic values for all the models used in this work when the bar is within approximately ten degrees of the major or minor axis.

  9. Sparse representation of MER signals for localizing the Subthalamic Nucleus in Parkinson's disease surgery.

    PubMed

    Vargas Cardona, Hernán Darío; Álvarez, Mauricio A; Orozco, Álvaro A

    2014-01-01

    Deep brain stimulation (DBS) of Subthalamic Nucleus (STN) is the best method for treating advanced Parkinson's disease (PD), leading to striking improvements in motor function and quality of life of PD patients. During DBS, online analysis of microelectrode recording (MER) signals is a powerful tool to locate the STN. Therapeutic outcomes depend of a precise positioning of a stimulator device in the target area. In this paper, we show how a sparse representation of MER signals allows to extract discriminant features, improving the accuracy in identification of STN. We apply three techniques for over-complete representation of signals: Method of Frames (MOF), Best Orthogonal Basis (BOB) and Basis Pursuit (BP). All the techniques are compared to classical methods for signal processing like Wavelet Transform (WT), and a more sophisticated method known as adaptive Wavelet with lifting schemes (AW-LS). We apply each processing method in two real databases and we evaluate its performance with simple supervised classifiers. Classification outcomes for MOF, BOB and BP clearly outperform WT and AW-LF in all classifiers for both databases, reaching accuracy values over 98%.

  10. Structure and assembly of an augmented Sm-like archaeal protein 14-mer.

    PubMed

    Mura, Cameron; Phillips, Martin; Kozhukhovsky, Anna; Eisenberg, David

    2003-04-15

    To better understand the roles of Sm proteins in forming the cores of many RNA-processing ribonucleoproteins, we determined the crystal structure of an atypical Sm-like archaeal protein (SmAP3) in which the conserved Sm domain is augmented by a previously uncharacterized, mixed alpha/beta C-terminal domain. The structure reveals an unexpected SmAP3 14-mer that is perforated by a cylindrical pore and is bound to 14 cadmium (Cd(2+)) ions. Individual heptamers adopt either "apical" or "equatorial" conformations that chelate Cd(2+) differently. SmAP3 forms supraheptameric oligomers (SmAP3)(n = 7,14,28) in solution, and assembly of the asymmetric 14-mer is modulated by differential divalent cation-binding in apical and equatorial subunits. Phylogenetic and sequence analyses substantiate SmAP3s as a unique subset of SmAPs. These results distinguish SmAP3s from other Sm proteins and provide a model for the structure and properties of Sm proteins >100 residues in length, e.g., several human Sm proteins.

  11. 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.

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

    PubMed Central

    Cioni, M.; Leboeuf, C.; Comoli, P.; Ginevri, F.

    2016-01-01

    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

  13. 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

  14. 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

  15. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses.

    PubMed

    Gould, W R; Baxi, S M; Schroeder, R; Peng, Y W; Leadley, R J; Peterson, J T; Perrin, L A

    2005-04-01

    Gas6 (encoded by growth arrest-specific gene 6) is a vitamin-K dependent protein highly homologous to coagulation protein S that is secreted from platelet alpha-granules and has recently been demonstrated to participate in platelet thrombus formation. The current study evaluated the contribution of each of the three known Gas6 receptors (Axl, Sky and Mer) in human and mouse platelet function. Flow cytometry analyses confirmed that all three receptors are present on both human and mouse platelets. Pre-incubation of human platelets with either an anti-Gas6 antibody or blocking antibodies to Sky or Mer inhibited platelet aggregation and degranulation responses to both ADP and the PAR-1 activating peptide, SFLLRN, by more than 80%. In contrast, a stimulatory anti-Axl antibody increased activation responses to these agonists, suggesting a potentiating role for Gas6 in platelet activation. Moreover, in a mouse model of thrombosis, administration of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight similar to clopidogrel but, unlike clopidogrel, produced no increase in template bleeding. Thus, Gas6 enhances platelet degranulation and aggregation responses through its known receptors, promoting platelet activation and mediating thrombus formation such that its inhibition prevents thrombosis without increasing bleeding. PMID:15733062

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa

    PubMed Central

    Wang, Dan; Huang, Shanqing; Liu, Pingying; Liu, Xichun; He, Yafeng; Chen, Weizhong; Hu, Qingyuan; Wei, Tianbiao; Gan, Jianhua; Ma, Jing; Chen, Hao

    2016-01-01

    The metalloprotein MerR is a mercury(II)-dependent transcriptional repressor-activator that responds to mercury(II) with extraordinary sensitivity and selectivity. It’s widely distributed in both Gram-negative and Gram-positive bacteria but with barely detectable sequence identities between the two sources. To provide structural basis for the considerable biochemical and biophysical experiments previously performed on Tn501 and Tn21 MerR from Gram-negative bacteria, we analyzed the crystal structure of mercury(II)-bound Tn501 MerR. The structure in the metal-binding domain provides Tn501 MerR with a high affinity for mercury(II) and the ability to distinguish mercury(II) from other metals with its unique planar trigonal coordination geometry, which is adopted by both Gram-negative and Gram-positive bacteria. The mercury(II) coordination state in the C-terminal metal-binding domain is transmitted through the allosteric network across the dimer interface to the N-terminal DNA-binding domain. Together with the previous mutagenesis analyses, the present data indicate that the residues in the allosteric pathway have a central role in maintaining the functions of Tn501 MerR. In addition, the complex structure exhibits significant differences in tertiary and quaternary structural arrangements compared to those of Bacillus MerR from Gram-positive bacteria, which probably enable them to function with specific promoter DNA with different spacers between −35 and −10 elements. PMID:27641146

  1. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Huang, Shanqing; Liu, Pingying; Liu, Xichun; He, Yafeng; Chen, Weizhong; Hu, Qingyuan; Wei, Tianbiao; Gan, Jianhua; Ma, Jing; Chen, Hao

    2016-09-01

    The metalloprotein MerR is a mercury(II)-dependent transcriptional repressor-activator that responds to mercury(II) with extraordinary sensitivity and selectivity. It’s widely distributed in both Gram-negative and Gram-positive bacteria but with barely detectable sequence identities between the two sources. To provide structural basis for the considerable biochemical and biophysical experiments previously performed on Tn501 and Tn21 MerR from Gram-negative bacteria, we analyzed the crystal structure of mercury(II)-bound Tn501 MerR. The structure in the metal-binding domain provides Tn501 MerR with a high affinity for mercury(II) and the ability to distinguish mercury(II) from other metals with its unique planar trigonal coordination geometry, which is adopted by both Gram-negative and Gram-positive bacteria. The mercury(II) coordination state in the C-terminal metal-binding domain is transmitted through the allosteric network across the dimer interface to the N-terminal DNA-binding domain. Together with the previous mutagenesis analyses, the present data indicate that the residues in the allosteric pathway have a central role in maintaining the functions of Tn501 MerR. In addition, the complex structure exhibits significant differences in tertiary and quaternary structural arrangements compared to those of Bacillus MerR from Gram-positive bacteria, which probably enable them to function with specific promoter DNA with different spacers between ‑35 and ‑10 elements.

  2. 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.

  3. 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.

  4. 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

  5. MERS-CoV at the Animal–Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation

    PubMed Central

    Funk, Anna L.; Goutard, Flavie Luce; Miguel, Eve; Bourgarel, Mathieu; Chevalier, Veronique; Faye, Bernard; Peiris, J. S. Malik; Van Kerkhove, Maria D.; Roger, Francois Louis

    2016-01-01

    Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely

  6. 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…

  7. 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.

  8. 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

  9. Reproducible Synthesis and High Porosity of mer-Zn(Im)2 (ZIF-10): Exploitation of an Apparent Double-Eight Ring Template.

    PubMed

    Ramirez, Joseph R; Yang, Haiyang; Kane, Christopher M; Ley, Amanda N; Holman, K Travis

    2016-09-21

    Reproducible synthesis of the elusive merlinoite (mer) topology of zinc imidazolate (mer-Zn(Im)2, or ZIF-10) has been achieved by employing a simple macrocyclic solute-MeMeCH2-as a kinetic template. The corresponding phase-pure material, mer-MeMeCH2@Zn16(Im)32, is confirmed to be porous and exhibits one of the highest experimental surface areas (1893 m(2)/g, BET) yet reported for any ZIF. The X-ray single crystal structure of mer-MeMeCH2@Zn16(Im)32·xsolvent reveals the role of the macrocyle as an 8-fold hydrogen bond acceptor in templating the requisite double-eight rings (d8r) of the mer framework.

  10. Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Abu Dhabi Emirate, United Arab Emirates.

    PubMed

    Yusof, Mohammed F; Eltahir, Yassir M; Serhan, Wissam S; Hashem, Farouk M; Elsayed, Elsaeid A; Marzoug, Bahaaeldin A; Abdelazim, Assem Si; Bensalah, Oum Keltoum A; Al Muhairi, Salama S

    2015-06-01

    High seroprevalence of Middle East respiratory syndrome corona virus (MERS-CoV) in dromedary camels has been previously reported in United Arab Emirates (UAE). However, the molecular detection of the virus has never been reported before in UAE. Of the 7,803 nasal swabs tested in the epidemiological survey, MERS-CoV nucleic acid was detected by real-time PCR in a total of 126 (1.6 %) camels. Positive camels were detected at the borders with Saudi Arabia and Oman and in camels' slaughter houses. MERS-CoV partial sequences obtained from UAE camels were clustering with human- and camel-derived MERS-CoV sequences in the same geographic area. Results provide further evidence of MERS-CoV zoonosis.

  11. 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.

  12. 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

  13. 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.

  14. Environmental conditions constrain the distribution and diversity of archaeal merA in Yellowstone National Park, Wyoming, U.S.A.

    PubMed

    Wang, Yanping; Boyd, Eric; Crane, Sharron; Lu-Irving, Patricia; Krabbenhoft, David; King, Susan; Dighton, John; Geesey, Gill; Barkay, Tamar

    2011-11-01

    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.

  15. 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

  16. 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

  17. Remote Robotic Geology: Learning from the MER-FIDO Field Test Site

    NASA Astrophysics Data System (ADS)

    Anderson, R. C.; Dohm, J. M.; Haldemann, A. F.; Bass, D. S.; Huntsberger, T. L.

    2002-12-01

    Understanding the geology of a region from a robotic platform can be a challenging and difficult task. In order to prepare the team of investigators and engineers for the upcoming 2003 Mars Exploration Rover (MER) Mission, a "blind" rover field test was performed August 10 - 19, 2002, using the Field Integrated Design and Operations (FIDO) Rover. The field site, which is located near Gray Mountain Arizona (approximately 40 miles north of Flagstaff), was chosen because it: (1) maximizes science return and permits rover trafficability, (2) is easily accessed via a well-maintained mining road, (3) occurs north of Flagstaff, Arizona, where seasonal temperatures are adequate for rover operations and climate records show minimal rainfall, (4) lacks vegetation (a very difficult variable for Earth), and (5) contains diverse geological terrains similar to what might be encountered on Mars, including claystones, siltsones, mudstones, and sandstones of the Shinarump Member of the Chinle Formation. that crop out among fluvially carved drainages, fluvial and eolian deposits that partly blanket the drainage floors, and cobbles and boulders of diverse petrology and geochemistry (e.g., basalt, chert, sandstone, limestone, metamorphic). The goal of the FIDO test was to teach the MER Science Team the techniques involved in conducting a geologic investigation with a remote rover. Inherent disadvantages associated with remote robotic exploration include a limited time-associated visibility to the site. This disadvantage is somewhat offset by the availability of instruments on the rover that might ordinarily be available to a geologist only in a laboratory setting. This talk will further explore the coupling of a remote robotic platform with what is known about the field site to provide insight into future robotic exploration of planetary locales.

  18. 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).

  19. 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

  20. Diminishing return for increased Mappability with longer sequencing reads: implications of the k-mer distributions in the human genome

    PubMed Central

    2014-01-01

    Background The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a longer read is more likely to be uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the k-mer distribution of the human reference genome. The k-mer frequency is determined for k ranging from 20 bp to 1000 bp. Results We observe that the proportion of non-singletons k-mers decreases slowly with increasing k, and can be fitted by piecewise power-law functions with different exponents at different ranges of k. A slower decay at greater values for k indicates more limited gains in mappability for read lengths between 200 bp and 1000 bp. The frequency distributions of k-mers exhibit long tails with a power-law-like trend, and rank frequency plots exhibit a concave Zipf’s curve. The most frequent 1000-mers comprise 172 regions, which include four large stretches on chromosomes 1 and X, containing genes of biomedical relevance. Comparison with other databases indicates that the 172 regions can be broadly classified into two types: those containing LINE transposable elements and those containing segmental duplications. Conclusion Read mappability as measured by the proportion of singletons increases steadily up to the length scale around 200 bp. When read length increases above 200 bp, smaller gains in mappability are expected. Moreover, the proportion of non-singletons decreases with read lengths much slower than linear. Even a read length of 1000 bp would not allow the unique alignment of reads for many coding regions of human genes. A mix of techniques will be needed for efficiently producing high-quality data that cover the complete human genome. PMID:24386976

  1. Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

    PubMed Central

    2013-01-01

    Introduction Systemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE. Methods Levels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry. Results Both sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure. Conclusions Alterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE. PMID:24325951

  2. 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

  3. 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.

  4. MIMOS II on MER One Year of Mossbauer Spectroscopy on the Surface of Mars: From Jarosite at Meridiani Planum to Goethite at Gusev Crater

    NASA Technical Reports Server (NTRS)

    Klingelhoefer, G.; Rodionov, D. S.; Morris, R. V.; Schroeder, C.; deSouza, P. A.; Ming, D. W.; Yen, A. S.; Bernhardt, B.; Renz, F.; Fleischer, I.

    2005-01-01

    The miniaturized Mossbauer (MB) spectrometer MIMOS II [1] is part of the Athena payload of NASA s twin Mars Exploration Rovers "Spirit" (MER-A) and "Opportunity" (MER-B). It determines the Fe-bearing mineralogy of Martian soils and rocks at the Rovers respective landing sites, Gusev crater and Meridiani Planum. Both spectrometers performed successfully during first year of operation. Total integration time is about 49 days for MERA (79 samples) and 34 days for MER-B (85 samples). For curiosity it might be interesting to mention that the total odometry of the oscillating part of the MB drive exceeds 35 km for both rovers.

  5. 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

  6. 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

  7. Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding.

    PubMed

    Adney, Danielle R; Brown, Vienna R; Porter, Stephanie M; Bielefeldt-Ohmann, Helle; Hartwig, Airn E; Bowen, Richard A

    2016-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses. PMID:27548203

  8. Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding

    PubMed Central

    Adney, Danielle R.; Brown, Vienna R.; Porter, Stephanie M.; Bielefeldt-Ohmann, Helle; Hartwig, Airn E.; Bowen, Richard A.

    2016-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses. PMID:27548203

  9. A FASTQ compressor based on integer-mapped k-mer indexing for biologist.

    PubMed

    Zhang, Yeting; Patel, Khyati; Endrawis, Tony; Bowers, Autumn; Sun, Yazhou

    2016-03-15

    Next generation sequencing (NGS) technologies have gained considerable popularity among biologists. For example, RNA-seq, which provides both genomic and functional information, has been widely used by recent functional and evolutionary studies, especially in non-model organisms. However, storing and transmitting these large data sets (primarily in FASTQ format) have become genuine challenges, especially for biologists with little informatics experience. Data compression is thus a necessity. KIC, a FASTQ compressor based on a new integer-mapped k-mer indexing method, was developed (available at http://www.ysunlab.org/kic.jsp). It offers high compression ratio on sequence data, outstanding user-friendliness with graphic user interfaces, and proven reliability. Evaluated on multiple large RNA-seq data sets from both human and plants, it was found that the compression ratio of KIC had exceeded all major generic compressors, and was comparable to those of the latest dedicated compressors. KIC enables researchers with minimal informatics training to take advantage of the latest sequence compression technologies, easily manage large FASTQ data sets, and reduce storage and transmission cost. PMID:26743127

  10. Duplex stabilities of phosphorothioate, methylphosphonate, and RNA analogs of two DNA 14-mers.

    PubMed Central

    Kibler-Herzog, L; Zon, G; Uznanski, B; Whittier, G; Wilson, W D

    1991-01-01

    The duplex stabilities of various phosphorothioate, methylphosphonate, RNA and 2'-OCH3 RNA analogs of two self-complementary DNA 14-mers are compared. Phosphorothioate and/or methylphosphonate analogs of the two sequences d(TAATTAATTAATTA) [D1] and d(TAGCTAATTAGCTA) [D2] differ in the number, position, or chirality (at the 5' terminal linkage) of the modified phosphates. Phosphorothioate derivatives of D1 are found to be less destabilized when the linkage modified is between adenines rather than between thymines. Surprisingly, no base sequence effect on duplex stabilization is observed for any methylphosphonate derivatives of D1 or D2. Highly modified phosphorothioates or methylphosphonates are less stable than their partially modified counterparts which are less stable than the unmodified parent compounds. The 'normal' (2'-OH) RNA analog of duplex D1 is slightly destabilized, whereas the 2'-OCH3 RNA derivative is significantly stabilized relative to the unmodified DNA. For the D1 sequence, at approximately physiological salt concentration, the order of duplex stability is 2'-OCH3 RNA greater than unmodified DNA greater than 'normal' RNA greater than methylphosphonate DNA greater than phosphorothioate DNA. D2 and the various D2 methylphosphonate analogs investigated all formed hairpin conformations at low salt concentrations. PMID:1711677

  11. Leveraging Cloud Computing to Improve Storage Durability, Availability, and Cost for MER Maestro

    NASA Technical Reports Server (NTRS)

    Chang, George W.; Powell, Mark W.; Callas, John L.; Torres, Recaredo J.; Shams, Khawaja S.

    2012-01-01

    The Maestro for MER (Mars Exploration Rover) software is the premiere operation and activity planning software for the Mars rovers, and it is required to deliver all of the processed image products to scientists on demand. These data span multiple storage arrays sized at 2 TB, and a backup scheme ensures data is not lost. In a catastrophe, these data would currently recover at 20 GB/hour, taking several days for a restoration. A seamless solution provides access to highly durable, highly available, scalable, and cost-effective storage capabilities. This approach also employs a novel technique that enables storage of the majority of data on the cloud and some data locally. This feature is used to store the most recent data locally in order to guarantee utmost reliability in case of an outage or disconnect from the Internet. This also obviates any changes to the software that generates the most recent data set as it still has the same interface to the file system as it did before updates

  12. Dissecting the Metal Selectivity of MerR Monovalent Metal Ion Sensors in Salmonella

    PubMed Central

    Ibáñez, María M.; Cerminati, Sebastián; Checa, Susana K.

    2013-01-01

    Two homologous transcription factors, CueR and GolS, that belong to the MerR metalloregulatory family are responsible for Salmonella Cu and Au sensing and resistance, respectively. They share similarities not only in their sequences, but also in their target transcription binding sites. While CueR responds similarly to Au, Ag, or Cu to induce the expression of its target genes, GolS shows higher activation by Au than by Ag or Cu. We showed that the ability of GolS to distinguish Au from Cu resides in the metal-binding loop motif. Here, we identify the amino acids within the motif that determine in vivo metal selectivity. We show that residues at positions 113 and 118 within the metal-binding loop are the main contributors to metal selectivity. The presence of a Pro residue at position 113 favors the detection of Cu, while the presence of Pro at position 118 disfavors it. Our results highlight the molecular bases that allow these regulators to coordinate the correct metal ion directing the response to a particular metal injury. PMID:23645605

  13. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    PubMed

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL. PMID:26820485

  14. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    PubMed

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  15. Monitoring the formation of kernel-based topographic maps in a hybrid SOM-kMER model.

    PubMed

    Teh, Chee Siong; Lim, Chee Peng

    2006-09-01

    A new lattice disentangling monitoring algorithm for a hybrid self-organizing map-kernel-based maximum entropy learning rule (SOM-kMER) model is proposed. It aims to overcome topological defects owing to a rapid decrease of the neighborhood range over the finite running time in topographic map formation. The empirical results demonstrate that the proposed approach is able to accelerate the formation of a topographic map and, at the same time, to simplify the monitoring procedure.

  16. Beta-arrestin-2 negatively modulates inflammation response in mouse chondrocytes induced by 4-mer hyaluronan oligosaccharide.

    PubMed

    Campo, Giuseppe M; Avenoso, Angela; D'Ascola, Angela; Scuruchi, Michele; Calatroni, Alberto; Campo, Salvatore

    2015-01-01

    Beta-arrestin-2 is an adaptor protein that terminates G protein activation and seems to be involved in the modulation of the inflammatory response. Small hyaluronan (HA) fragments, such as 4-mer HA oligosaccharides, are known to interact with the toll-like receptor-4 (TLR-4) with consequent activation of the nuclear factor kappaB (NF-kB) that in turn stimulates the inflammation response. NF-kB activation is mediated by different pathways, in particular by the transforming growth factor-activated kinase-1 (TAK-1). Conversely, increased levels of protein kinase A (PKA), induced by cyclic adenosine monophosphate (cAMP), seem to inhibit NF-kB activation. We studied the involvement and role of beta-arrestin-2 in mouse chondrocytes stimulated with 4-mer HA fragments. The exposure of chondrocytes to 4-mer HA produced a significant up-regulation in TLR-4, cAMP, beta-arrestin-2, TAK-1, protein 38 mitogen-activated protein kinase (p38MAPK), and PKA, both in terms of mRNA expression and of the related protein levels. NF-kB was significantly activated, thereby producing the transcription of pro-inflammatory mediators, including tumor necrosis factor alpha, interleukin-6, and interleukin-17. The treatment of 4-mer HA-stimulated chondrocytes with antibodies against beta-arrestin-2 and/or a specific PKA inhibitor, significantly increased the inflammatory response, while the treatment with a specific p38MAPK inhibitor significantly reduced the inflammatory response. Interestingly, the anti-inflammatory action exerted by beta-arrestin-2 appeared to be mediated in part through the direct inhibition of p38MAPK, preventing NF-kB activation, and in part through cAMP and PKA activation primed by G protein signaling, which exerted an inhibitory effect on NF-kB. Taken together, these results could be useful for future anti-inflammatory strategies. PMID:25318610

  17. Beta-arrestin-2 negatively modulates inflammation response in mouse chondrocytes induced by 4-mer hyaluronan oligosaccharide.

    PubMed

    Campo, Giuseppe M; Avenoso, Angela; D'Ascola, Angela; Scuruchi, Michele; Calatroni, Alberto; Campo, Salvatore

    2015-01-01

    Beta-arrestin-2 is an adaptor protein that terminates G protein activation and seems to be involved in the modulation of the inflammatory response. Small hyaluronan (HA) fragments, such as 4-mer HA oligosaccharides, are known to interact with the toll-like receptor-4 (TLR-4) with consequent activation of the nuclear factor kappaB (NF-kB) that in turn stimulates the inflammation response. NF-kB activation is mediated by different pathways, in particular by the transforming growth factor-activated kinase-1 (TAK-1). Conversely, increased levels of protein kinase A (PKA), induced by cyclic adenosine monophosphate (cAMP), seem to inhibit NF-kB activation. We studied the involvement and role of beta-arrestin-2 in mouse chondrocytes stimulated with 4-mer HA fragments. The exposure of chondrocytes to 4-mer HA produced a significant up-regulation in TLR-4, cAMP, beta-arrestin-2, TAK-1, protein 38 mitogen-activated protein kinase (p38MAPK), and PKA, both in terms of mRNA expression and of the related protein levels. NF-kB was significantly activated, thereby producing the transcription of pro-inflammatory mediators, including tumor necrosis factor alpha, interleukin-6, and interleukin-17. The treatment of 4-mer HA-stimulated chondrocytes with antibodies against beta-arrestin-2 and/or a specific PKA inhibitor, significantly increased the inflammatory response, while the treatment with a specific p38MAPK inhibitor significantly reduced the inflammatory response. Interestingly, the anti-inflammatory action exerted by beta-arrestin-2 appeared to be mediated in part through the direct inhibition of p38MAPK, preventing NF-kB activation, and in part through cAMP and PKA activation primed by G protein signaling, which exerted an inhibitory effect on NF-kB. Taken together, these results could be useful for future anti-inflammatory strategies.

  18. Mutagenesis of the C1 Oxidation Pathway in Methanosarcina barkeri: New Insights into the Mtr/Mer Bypass Pathway▿

    PubMed Central

    Welander, Paula V.; Metcalf, William W.

    2008-01-01

    A series of Methanosarcina barkeri mutants lacking the genes encoding the enzymes involved in the C1 oxidation/reduction pathway were constructed. Mutants lacking the methyl-tetrahydromethanopterin (H4MPT):coenzyme M (CoM) methyltransferase-encoding operon (Δmtr), the methylene-H4MPT reductase-encoding gene (Δmer), the methylene-H4MPT dehydrogenase-encoding gene (Δmtd), and the formyl-methanofuran:H4MPT formyl-transferase-encoding gene (Δftr) all failed to grow using either methanol or H2/CO2 as a growth substrate, indicating that there is an absolute requirement for the C1 oxidation/reduction pathway for hydrogenotrophic and methylotrophic methanogenesis. The mutants also failed to grow on acetate, and we suggest that this was due to an inability to generate the reducing equivalents needed for biosynthetic reactions. Despite their lack of growth on methanol, the Δmtr and Δmer mutants were capable of producing methane from this substrate, whereas the Δmtd and Δftr mutants were not. Thus, there is an Mtr/Mer bypass pathway that allows oxidation of methanol to the level of methylene-H4MPT in M. barkeri. The data further suggested that formaldehyde may be an intermediate in this bypass; however, no methanol dehydrogenase activity was found in Δmtr cell extracts, nor was there an obligate role for the formaldehyde-activating enzyme (Fae), which has been shown to catalyze the condensation of formaldehyde and H4MPT in vitro. Both the Δmer and Δmtr mutants were able to grow on a combination of methanol plus acetate, but they did so by metabolic pathways that are clearly distinct from each other and from previously characterized methanogenic pathways. PMID:18178739

  19. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

    PubMed Central

    Shiri, Fereshteh; Pirhadi, Somayeh; Ghasemi, Jahan B.

    2015-01-01

    Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q2 value of 0.77, an rpred2 of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors. PMID:27013913

  20. Possible Evidence for Iron Sulfates, Iron Sulfides, and Elemental Sulfur at Gusev Crater, Mars, from Mer, Crism, and Analog Data

    NASA Technical Reports Server (NTRS)

    Morris, R. V.; Ming, D. W.; Yen, A.; Arvidson, R. E.; Gruener, J.; Humm, D.; Klingelhoefer, G.; Murchie, S.; Schroeder, C.; Seelos, F., IV; Squyres, S.; Wiseman, S.; Wolff, M.

    2007-01-01

    The Mossbauer (MB) spectrometers on the Mars Exploration Rovers (MER) Spirit (Gusev crater) and Opportunity (Meridiani Planum) have detected 14 Fe-bearing phases, and mineralogical assignments have been made for all except 3. Identified Fe2+-bearing phases are olivine, pyroxene, ilmenite, and troilite. Magnetite and chromite are present as mixed Fe(2+) and Fe(3+) phases. Identified Fe(3+) phase are jarosite, hematite, goethite, and nanophase ferric oxide (npOx). Fe(sup 0) (iron metal) is present as kamacite. Nanophase ferric oxide (npOx) is a generic name for octahedrally coordinated Fe(3+) alteration products that cannot be otherwise mineralogically assigned on the basis of MER data. On the Earth, npOx would include ferrihydrite, iddingsite, schwertmannite, akaganeite, and superparamagnetic hematite and goethite. The Mars Reconnaissance Orbiter CRISM instrument, a visible, near-IR hyperspectral imager (approximately 0.35 to 4 micron) enables mineralogical examination of Mars with a tool that is sensitive to H2O and to M-OH (M = Al, Si, Fe, Mg, etc.) at spatial resolution of about 20 m/pixel. We examined a CRISM image of the MER region of Gusev crater (Columbia Hills and plains to the west), looking for spectral evidence of the aqueous process apparent from the MER analyses. We also searched for spectral constraints for the mineralogical composition of our unidentified Fe-bearing phases and the forms of npOx present on Mars. We also consider evidence from analogue samples that the precursor for the goethite detected by MB in Clovis Class rocks is an iron sulfide. We suggest that there is some indirect evidence that elemental sulfur might be present to different extents in Clovis Class rocks, the Fe3Sulfate-rich soils, and perhaps even typical (Laguna Class) surface soils.

  1. STN area detection using K-NN classifiers for MER recordings in Parkinson patients during neurostimulator implant surgery

    NASA Astrophysics Data System (ADS)

    Schiaffino, L.; Rosado Muñoz, A.; Guerrero Martínez, J.; Francés Villora, J.; Gutiérrez, A.; Martínez Torres, I.; Kohan, y. D. R.

    2016-04-01

    Deep Brain Stimulation (DBS) applies electric pulses into the subthalamic nucleus (STN) improving tremor and other symptoms associated to Parkinson’s disease. Accurate STN detection for proper location and implant of the stimulating electrodes is a complex task and surgeons are not always certain about final location. Signals from the STN acquired during DBS surgery are obtained with microelectrodes, having specific characteristics differing from other brain areas. Using supervised learning, a trained model based on previous microelectrode recordings (MER) can be obtained, being able to successfully classify the STN area for new MER signals. The K Nearest Neighbours (K-NN) algorithm has been successfully applied to STN detection. However, the use of the fuzzy form of the K-NN algorithm (KNN-F) has not been reported. This work compares the STN detection algorithm of K-NN and KNN-F. Real MER recordings from eight patients where previously classified by neurophysiologists, defining 15 features. Sensitivity and specificity for the classifiers are obtained, Wilcoxon signed rank non-parametric test is used as statistical hypothesis validation. We conclude that the performance of KNN-F classifier is higher than K-NN with p<0.01 in STN specificity.

  2. Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia

    PubMed Central

    Virlogeux, Victor; Fang, Vicky J.; Park, Minah; Wu, Joseph T.; Cowling, Benjamin J.

    2016-01-01

    The incubation period is an important epidemiologic distribution, it is often incorporated in case definitions, used to determine appropriate quarantine periods, and is an input to mathematical modeling studies. Middle East Respiratory Syndrome coronavirus (MERS) is an emerging infectious disease in the Arabian Peninsula. There was a large outbreak of MERS in South Korea in 2015. We examined the incubation period distribution of MERS coronavirus infection for cases in South Korea and in Saudi Arabia. Using parametric and nonparametric methods, we estimated a mean incubation period of 6.9 days (95% credibility interval: 6.3–7.5) for cases in South Korea and 5.0 days (95% credibility interval: 4.0–6.6) among cases in Saudi Arabia. In a log-linear regression model, the mean incubation period was 1.42 times longer (95% credibility interval: 1.18–1.71) among cases in South Korea compared to Saudi Arabia. The variation that we identified in the incubation period distribution between locations could be associated with differences in ascertainment or reporting of exposure dates and illness onset dates, differences in the source or mode of infection, or environmental differences. PMID:27775012

  3. Flow cytometry and K-mer analysis estimates of the genome sizes of Bemisia tabaci B and Q (Hemiptera: Aleyrodidae)

    PubMed Central

    Guo, Li T.; Wang, Shao L.; Wu, Qing J.; Zhou, Xu G.; Xie, Wen; Zhang, You J.

    2015-01-01

    The genome sizes of the B- and Q-types of the whitefly Bemisia tabaci (Gennnadius) were estimated using flow cytometry (Drosophila melanogaster as the DNA reference standard and propidium iodide (PI) as the fluorochrome) and k-mer analysis. For flow cytometry, the mean nuclear DNA content was 0.686 pg for B-type males, 1.392 pg for B-type females, 0.680 pg for Q-type males, and 1.306 pg for Q-type females. Based on the relationship between DNA content and genome size (1 pg DNA = 980 Mbp), the haploid genome size of B. tabaci ranged from 640 to 682 Mbp. For k-mer analysis, genome size of B-type by two methods were consistent highly, but the k-mer depth distribution graph of Q-type was not enough perfect and the genome size was estimated about 60 M larger than its flow cytometry result. These results corroborate previous reports of genome size based on karyotype analysis and chromosome counting. However, these estimates differ from previous flow cytometry estimates, probably because of differences in the DNA reference standard and dyeing time, which were superior in the current study. For Q-type genome size difference by two method, some discussion were also stated, and all these results represent a useful foundation for B. tabaci genomics research. PMID:26042041

  4. Montmorillonite Catalysis of 30-50 Mer Oligonucleotides: Laboratory Demonstration of Potential Steps in the Origin of the RNA World

    NASA Astrophysics Data System (ADS)

    Ferris, James P.

    2002-08-01

    Elongation of the primer 32pdA(pdA)8pA proceeds by the reaction of the 5'-phosphorimidazolides of adenosine and uridine in the presence of montmorillonite clay. Daily addition of the activated nucleotides for up to 14 days results in the formation of 40-50 mers using the 5'-phosphorimidazolide of adenosine (ImpA) and 25-30 mers using the 5'-phosphorimidazolide of uridine (ImpU). The limitation on the lengths of the chains formed is not due to the inhibitors formed since the same chain lengths were formed using 2-3 times the amount of montmorillonite catalyst. The shorter oligomers formed by the addition of U monomers is not due to its greater rate of decomposition since it was found that both the A and the U adducts decompose at about the same rates. Alkaline phosphatase hydrolysis studies revealed that some of the oligomers are capped at the 5'-end to form, with ImpA, Ap32pdA(pdA)8pA(pA)n. The extent of capping depends on the reaction time and the purine or pyrimidine base in the activated mononucleotide. Hydrolysis with ribonuclease T2 followed by alkaline phosphatase determined the sites of the 3', 5'- and 2', 5'-phosphodiester bonding to the primer. The potential significance of the mineral catalyzed formation of 50 mer oligonucleotides to the origin of life based on RNA (the RNA world scenario) is discussed.

  5. Efficacy of an Automated Multiple Emitter Whole-Room Ultraviolet-C Disinfection System Against Coronaviruses MHV and MERS-CoV.

    PubMed

    Bedell, Kurt; Buchaklian, Adam H; Perlman, Stanley

    2016-05-01

    Efficient and automated methods of disinfecting surfaces contaminated with the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) may prevent the spread of the virus. Here we report the efficacy and use of an automated triple-emitter whole room UV-C disinfection system to inactivate mouse hepatitis virus, strain A59 (MHV-A59) and MERS-CoV viruses on surfaces with a >5 log10 reduction.

  6. Crystal structures of the organomercurial lyase MerB in its free and mercury-bound forms: insights into the mechanism of methylmercury degradation.

    PubMed

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

    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-A resolution) and mercury-bound (1.64-A 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. PMID:19004822

  7. Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES.

    PubMed

    Cho, Chao-Cheng; Lin, Meng-Hsuan; Chuang, Chien-Ying; Hsu, Chun-Hua

    2016-03-01

    The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other CoVs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human CoVs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.

  8. Using Mars and the Mer Mission to Teach Science: A Curriculum Designed for Teachers and Their Students

    NASA Astrophysics Data System (ADS)

    Aubele, J. C.; Stanley, J.; Grochowski, A.; Jones, K.; Aragon, J.

    2006-12-01

    Learning opportunities can be exceptionally successful when linked to national, newsworthy events. Planetary missions are particularly exciting in engaging teachers, and their students, because they combine the human "stories" of scientists and engineers with cutting-edge technology and new science. Planetary suface missions, such as the Mars Exploration Rover (MER) mission, return beautiful and human-scale images that can virtually transport the viewer to another world. The MER mission allows children and adults to participate in the exploration of one of our nearest neighbors in space. New discoveries in the natural history of Mars have been used as the basis of a new integrated curriculum created by Museum and class-room educators designed to serve informal (family learning) and formal (classroom) audiences. The curriculum uses Mars and the MER mission as a "hook" to teach a wide range of topics that relate to all of the sciences, mathematics, social studies (history and exploration), science and society, career readiness, language and literacy, and visual arts. The curriculum, entitled "Making Tracks on Mars: Teacher Resource and Activity Guide," includes the following key features that have contributed to its success and usefulness: (1) basic information about Mars, Mars missions, and the MER mission providing teachers with the knowledge they may lack; (2) activities that follow a standardized format and include necessary information, pre-lesson preparation and post-lesson closure and extensions, and all information and/or images needed; (3) activities that cross the curriculum and can be used to address many different standards; (4) relevant state and national standards listed for each activity; (5) annotated MER image file and PowerPoint presentation for easy classroom use; (6) lists of additional Mars-related resources; (7) emphasis on local connections to the mission to enable teachers and students to feel personally connected; (8) elementary through high

  9. Effect of the antiestrogen ethamoxytriphetol (MER-25) on placental low density lipoprotein uptake and degradation in baboons

    SciTech Connect

    Henson, M.C.; Babischkin, J.S.; Pepe, G.J.; Albrecht, E.D.

    1988-05-01

    The present study determined if the decline in placental progesterone (P4) production that results from administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons results from a change in placental low density lipoprotein (LDL) uptake and/or degradation. Pregnant baboons (Papio anubis) were untreated (n = 10) or received MER-25 (25 mg/kg BW, orally; n = 10) daily on days 140-170 of gestation (term, 184 days). Placentas were removed by cesarean section on day 170 of gestation, and villous tissue was dispersed with 0.1% collagenase at 37 C for 40 min. Placental cells (10(6)) were incubated in medium 199 (pH 7.2) for 12 h at 37 C with increasing amounts (5-100 micrograms) of (125I)LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SE) peripheral serum P4 concentrations on days 140-170 of gestation were 51% lower (P less than 0.01) in MER-25-treated (5.7 +/- 0.3 ng/ml) than in untreated (11.6 +/- 0.5 ng/ml) baboons. The uptake of LDL was 56% lower (P less than 0.01) in placental cells from antiestrogen-treated (6.3 +/- 1.6 ng/micrograms cell protein) than in those from untreated (14.4 +/- 1.9 ng/micrograms cell protein) baboons. The dissociation constants for placental LDL uptake, as assessed by Scatchard analysis, however, were similar in untreated (0.80 microgram/ml) and MER-25-treated (0.76 microgram/ml) animals. The amount of (125I)LDL concomitantly degraded by cells from baboons that received MER-25 was 54% of that degraded by cells from untreated controls. The relative decline in LDL degradation by cells of antiestrogen-treated baboons was proportionate to the decline in overall LDL uptake. The results indicate, therefore, that antiestrogen treatment decreased the amount of placental LDL uptake, but did not change the affinity for the lipoprotein.

  10. Automated Recognition of Geologically Significant Shapes in MER PANCAM and MI Images

    NASA Technical Reports Server (NTRS)

    Morris, Robert; Shipman, Mark; Roush, Ted L.

    2004-01-01

    Autonomous recognition of scientifically important information provides the capability of: 1) Prioritizing data return; 2) Intelligent data compression; 3) Reactive behavior onboard robotic vehicles. Such capabilities are desirable as mission scenarios include longer durations with decreasing interaction from mission control. To address such issues, we have implemented several computer algorithms, intended to autonomously recognize morphological shapes of scientific interest within a software architecture envisioned for future rover missions. Mars Exploration Rovers (MER) instrument payloads include a Panoramic Camera (PANCAM) and Microscopic Imager (MI). These provide a unique opportunity to evaluate our algorithms when applied to data obtained from the surface of Mars. Early in the mission we applied our algorithms to images available at the mission web site (http://marsrovers.jpl.nasa.gov/gallery/images.html), even though these are not at full resolution. Some algorithms would normally use ancillary information, e.g. camera pointing and position of the sun, but these data were not readily available. The initial results of applying our algorithms to the PANCAM and MI images are encouraging. The horizon is recognized in all images containing it; such information could be used to eliminate unwanted areas from the image prior to data transmission to Earth. Additionally, several rocks were identified that represent targets for the mini-thermal emission spectrometer. Our algorithms also recognize the layers, identified by mission scientists. Such information could be used to prioritize data return or in a decision-making process regarding future rover activities. The spherules seen in MI images were also autonomously recognized. Our results indicate that reliable recognition of scientifically relevant morphologies in images is feasible.

  11. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

    PubMed

    Otter, J A; Donskey, C; Yezli, S; Douthwaite, S; Goldenberg, S D; Weber, D J

    2016-03-01

    Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings. PMID:26597631

  12. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

    PubMed

    Otter, J A; Donskey, C; Yezli, S; Douthwaite, S; Goldenberg, S D; Weber, D J

    2016-03-01

    Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.

  13. IFITM Proteins Inhibit Entry Driven by the MERS-Coronavirus Spike Protein: Evidence for Cholesterol-Independent Mechanisms

    PubMed Central

    Wrensch, Florian; Winkler, Michael; Pöhlmann, Stefan

    2014-01-01

    The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS- and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs. PMID:25256397

  14. Rock and Soil Physical Properties at the MER Gusev Crater and Meridiani Planum Landing Sites

    NASA Astrophysics Data System (ADS)

    Richter, L.; Arvidson, R.; Bell, J.; Cabrol, N.; Gorevan, S.; Greeley, R.; Herkenhoff, K.; Ming, D.; Sullivan, R.; Mer Athena Science Team

    Following the successful landings of both Mars Exploration Rover (MER) vehicles at Gusev Crater and Meridiani Planum, respectively, their Athena suite of instruments is being used to study the geologic history of these two very different landing sites on Mars that had been selected on the basis of showing different types of evidence for aqueous processes in the planet's past. Utilizing the on-board instruments as well as the rovers' mobility system, a wide range of physical properties investigations is carried out as well -- the subject of this abstract - that provide additional information on the geology and processes at the sites. Results of the mission in general as well as of the physical properties studies thus far greatly exceed expectations in that observations and measurements by both vehicles show a rich variety in materials and processes: the Gusev site in the vicinity of the lander is remarkably flat and generally devoid of large rocks along traverses up to the time of this writing (˜ Sol 50) and suggestive of a deflated surface with generally only thin veneers of bright dust while exhibiting evidence of a widespread occurrence of a crust from cemented fines that has been observed to fail in the form of blocky clods when disturbed by vehicle rolling action; numerous small and shallow depressions -- presumably created by impacts - are observed at the site which are infilled with bright, fine-grained material that likewise appears indurated and which was studied by a trenching experiment; small ripple bedforms are scattered across the site and were characterized in terms of particle size distributions. At the Meridiani site, studies so far -- up to ˜ Sol 33 -- have focussed on soils and the rock outcrop encountered within the ˜ 20 m diameter crater that the spacecraft came to rest in: from a physical properties point of view, a mantle of dark, well-sorted, apparently basaltic sand with small to moderate cohesion has been of interest -- and has been

  15. ROCK AND SOIL PHYSICAL PROPERTIES AT THE MER GUSEV CRATER AND MERIDIANI PLANUM LANDING SITES

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W.; Richter, L.; Arvidson, R.; Bell, J.; Cabrol, N.; Gorevan, S.; Greeley, R.; Herkenhoff, K.

    2006-01-01

    Following the successful landings of both Mars Exploration Rover (MER) vehicles at Gusev Crater and Meridiani Planum, respectively, their Athena suite of instruments is being used to study the geologic history of these two very different landing sites on Mars that had been selected on the basis of showing different types of evidence for aqueous processes in the planet s past. Utilizing the on-board instruments as well as the rovers mobility system, a wide range of physical properties investigations is carried out as well - the subject of this abstract - that provide additional information on the geology and processes at the sites. Results of the mission in general as well as of the physical properties studies thus far greatly exceed expectations in that observations and measurements by both vehicles show a rich variety in materials and processes: the Gusev site in the vicinity of the lander is remarkably flat and generally devoid of large rocks along traverses up to the time of this writing (approx.Sol 50) and suggestive of a deflated surface with generally only thin veneers of bright dust while exhibiting evidence of a widespread occurrence of a crust from cemented fines that has been observed to fail in the form of blocky clods when disturbed by vehicle rolling action; numerous small and shallow depressions - presumably created by impacts - are observed at the site which are infilled with bright, fine-grained material that likewise appears indurated and which was studied by a trenching experiment; small ripple bedforms are scattered across the site and were characterized in terms of particle size distributions. At the Meridiani site, studies so far - up to approx.Sol 33 - have focussed on soils and the rock outcrop encountered within the approx.20 m diameter crater that the spacecraft came to rest in: from a physical properties point of view, a mantle of dark, well-sorted, apparently basaltic sand with small to moderate cohesion has been of interest - and has

  16. An In-Situ Rb-Sr Dating & Organics Characterization Instrument For A MER+ Sized Rover

    NASA Astrophysics Data System (ADS)

    Anderson, F.; Whitaker, T.; Nowicki, K.; Zacny, K.; Pierce, J.

    2012-12-01

    We posit that a Mars in-situ geochronology mission that will triage and validate samples for Mars Sample Return (MSR) is technically feasible in the 2018-2022 time frame and addresses the competing scientific, political, and fiscal requirements for flight in this decade.The mission must be responsive to the astrobiological and chronological science goals of the MEPAG, Decadal Survey (DS), and E2E-iSAG, and avoid the MSR appearance of long term political commitment and cost. These requirements can best be accomplished by a rover with a coring drill. JPL has reassessed the MER landing system performance, and determined that the system is capable of significantly higher landed mass (~40-60 kg plus reserve), allowing more sophisticated instruments to be carried. The instrument package is comprised of a time of flight (TOF) mass spectrometer combined with a laser desorption resonance ionization source to sensitively measure isobar free Rb-Sr isotopes for geochronology and organics characterization. The desorption laser is also used with a μRaman/LIBS for mineral characterization, which in combination with the TOF, will additionally provide measurements of K-Ar isotopes for a second form of radiometric dating. The laser desorption resonance ionization mass spectrometry (LDRIMS) technique avoids the interference and mass resolution issues associated with geochronology measurements, and has miniaturization potential. A sample is placed in the TOF mass spectrometer and surface atoms, molecules, and ions are desorbed with a 213 nm laser. Ions are suppressed by an electric field and the plume of expanding particles is present for many μs, during which it is first illuminated with laser light tuned to ionize only Sr, and then 1-3 μs later, for Rb. We have partially miniaturized the instrument, including Sr lasers, ablation laser, and mass spectrometer, and will soon to start using the instrument for field measurements. Our current prototype can measure the isotope ratio of

  17. Modelling impacts of offshore wind farms on trophic web: the Courseulles-sur-Mer case study

    NASA Astrophysics Data System (ADS)

    Raoux, Aurore; Pezy, Jean-Philippe; Dauvin, Jean-Claude; Tecchio, samuele; Degraer, Steven; Wilhelmsson, Dan; Niquil, Nathalie

    2016-04-01

    The French government is planning the construction of three offshore wind farms in Normandy. These offshore wind farms will integrate into an ecosystem already subject to a growing number of anthropogenic disturbances such as transportation, fishing, sediment deposit, and sediment extraction. The possible effects of this cumulative stressors on ecosystem functioning are still unknown, but they could impact their resilience, making them susceptible to changes from one stable state to another. Understanding the behaviour of these marine coastal complex systems is essential in order to anticipate potential state changes, and to implement conservation actions in a sustainable manner. Currently, there are no global and integrated studies on the effects of construction and exploitation of offshore wind farms. Moreover, approaches are generally focused on the conservation of some species or groups of species. Here, we develop a holistic and integrated view of ecosystem impacts through the use of trophic webs modelling tools. Trophic models describe the interaction between biological compartments at different trophic levels and are based on the quantification of flow of energy and matter in ecosystems. They allow the application of numerical methods for the characterization of emergent properties of the ecosystem, also called Ecological Network Analysis (ENA). These indices have been proposed as ecosystem health indicators as they have been demonstrated to be sensitive to different impacts on marine ecosystems. We present here in detail the strategy for analysing the potential environmental impacts of the construction of the Courseulles-sur-Mer offshore wind farm (Bay of Seine) such as the reef effect through the use of the Ecopath with Ecosim software. Similar Ecopath simulations will be made in the future on the Le Tréport offshore wind farm site. Results will contribute to a better knowledge of the impacts of the offshore wind farms on ecosystems. They also allow to

  18. Proglacial sediment supply and channel evolution of the Arveyron of the Mer de Glace since the early 20th c.

    NASA Astrophysics Data System (ADS)

    Berthet, Johan; Astrade, Laurent; Ravanel, Ludovic; Ployon, Estelle

    2015-04-01

    The Arveyron of the Mer de Glace is the emissary of the most famous and largest French glacier. The latter has dramatically shrunk since the end of the Little Ice Age (LIA), such as every alpine glacier: the front has registered a retreat of 2.7 km since 1820 and a recent modelling showed a likely decrease of an extra km by 2040. The Arveyron and its surroundings are deeply impacted by the retreat. Then, dynamics of proglacial streams and of lateral moraines have been studied at different time and space scales through various methods: airborne and terrestrial Lidar DEM comparisons, mapping from orthophotos, 2D and 3D monoplotting to quantify past events from old terrestrial pictures, etc. By coupling studies on moraines and on stream morphology we wanted to better understand the influence of glacier retreat on sediment supply and transport downstream. Results show the evolution of the stream sediment sources linked to the glacier retreat. Before the middle of the 20th century, till was the main sediment source and was released by major flood events such as GLOFs. Now, geomorphic activity is especially important on the right lateral moraine into the recently deglaciated hanging valley of the Mer de Glace but also in the moraine flanks of the current glacier tongue (many landslides occurred during the Summer 2014). The recent glacier retreat has also formed sediments sinks such as two proglacial lakes which are progressively filling. These lakes work as big sediment traps until they will disappear (around 2017). Fluvial dynamics of the Arveyron depends on the connectivity with potential sediments sources. This is why we crossed upstream studies with the channel evolution on its fan. Arveyron channel has got narrower and incised for at least a century. Such evolution should mean a decreasing sediment yield, but anthropic factors play also an important role on stream morphology. The main anthorpic impact is the complex subglacial harnessing of the Mer de Glace. The

  19. Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin.

    PubMed

    Lei, Jian; Hilgenfeld, Rolf

    2016-08-01

    The papain-like protease (PL(pro)) of Middle-East respiratory syndrome coronavirus (MERS-CoV) has proteolytic, deubiquitinating, and deISGylating activities. The latter two are involved in the suppression of the antiviral innate immune response of the host cell. To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. Five regions of the PL(pro) bind to two areas of the Ub. The C-terminal five residues of Ub, RLRGG, are similar to the P5-P1 residues of the polyprotein substrates of the PL(pro) and are responsible for the major part of the interaction between the two macromolecules. Through sitedirected mutagenesis, we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL(pro). The enzyme appears not to be optimized for catalytic efficiency; thus, replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities. Ubiquitin binding by MERS-CoV PL(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL(pro). The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL(pro). PMID:27245450

  20. Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV).

    PubMed

    Zumla, Alimuddin; Alagaili, Abdulaziz N; Cotten, Matthew; Azhar, Esam I

    2016-01-01

    Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a "One Health" global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats. PMID:27604081

  1. Finding a human telomere DNA-RNA hybrid G-quadruplex formed by human telomeric 6-mer RNA and 16-mer DNA using click chemistry: a protective structure for telomere end.

    PubMed

    Xu, Yan; Suzuki, Yuta; Ishizuka, Takumi; Xiao, Chao-Da; Liu, Xiao; Hayashi, Tetsuya; Komiyama, Makoto

    2014-08-15

    Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in mammalian cells. The telomere RNA has been found to localize to the telomere DNA, but how the newly discovered RNA molecule interacts with telomere DNA is less known. In this study, using the click chemistry we successfully found that a 6-mer human telomere RNA and 16-mer human telomere DNA sequence can form a DNA-RNA hybrid type G-quadruplex structure. Detection of the click-reaction products directly probes DNA-RNA G-quadruplex structures in a complicated solution, whereas traditional methods such as NMR and crystallography may not be suitable. Importantly, we found that formation of DNA-RNA G-quadruplex induced an exonuclease resistance for telomere DNA, indicating that such structures might be important for protecting telomeric DNA from enzyme digestion to avoid telomere DNA shortening. These results provide the direct evidence for formation of DNA-RNA hybrid G-quadruplex structure by human telomere DNA and RNA sequence, suggesting DNA-RNA hybrid G-quadruplex structure associated between telomere DNA and RNA may respond to chromosome end protection and/or present a valuable target for drug design.

  2. An ensemble distance measure of k-mer and Natural Vector for the phylogenetic analysis of multiple-segmented viruses.

    PubMed

    Huang, Hsin-Hsiung

    2016-06-01

    The Natural Vector combined with Hausdorff distance has been successfully applied for classifying and clustering multiple-segmented viruses. Additionally, k-mer methods also yield promising results for global genome comparison. It is not known whether combining these two approaches can lead to more accurate results. The author proposes a method of combining the Hausdorff distances of the 5-mer counting vectors and natural vectors which achieves the best classification without cutting off any sample. Using the proposed method to predict the taxonomic labels for the 2363 NCBI reference viral genomes dataset, the accuracy rates are 96.95%, 94.37%, 99.41% and 93.82% for the Baltimore, family, subfamily, and genus labels, respectively. We further applied the proposed method to 48 isolates of the influenza A H7N9 viruses which have eight complete segments of nucleotide sequences. The single-linkage clustering trees and the statistical hypothesis testing results all indicate that the proposed ensemble distance measure can cluster viruses well using all of their segments of genome sequences.

  3. Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata.

    PubMed

    Kusche, Kristina; Hembach, Anne; Hagner-Holler, Silke; Gebauer, Wolfgang; Burmester, Thorsten

    2003-07-01

    Hemocyanins are large oligomeric copper-containing proteins that serve for the transport of oxygen in many arthropod species. While studied in detail in the Chelicerata and Crustacea, hemocyanins had long been considered unnecessary in the Myriapoda. Here we report the complete molecular structure of the hemocyanin from the common house centipede Scutigera coleoptrata (Myriapoda: Chilopoda), as deduced from 2D-gel electrophoresis, MALDI-TOF mass spectrometry, protein and cDNA sequencing, and homology modeling. This is the first myriapod hemocyanin to be fully sequenced, and allows the investigation of hemocyanin structure-function relationship and evolution. S. coleoptrata hemocyanin is a 6 x 6-mer composed of four distinct subunit types that occur in an approximate 2 : 2 : 1 : 1 ratio and are 49.5-55.5% identical. The cDNA of a fifth, highly diverged, putative hemocyanin was identified that is not included in the native 6 x 6-mer hemocyanin. Phylogenetic analyses show that myriapod hemocyanins are monophyletic, but at least three distinct subunit types evolved before the separation of the Chilopoda and Diplopoda more than 420 million years ago. In contrast to the situation in the Crustacea and Chelicerata, the substitution rates among the myriapod hemocyanin subunits are highly variable. Phylogenetic analyses do not support a common clade of Myriapoda and Hexapoda, whereas there is evidence in favor of monophyletic Mandibulata.

  4. Contribution aux etudes de signaux radar de surfaces de mer et mise au point d'un traitement rapide

    NASA Astrophysics Data System (ADS)

    Jousselme, Anne-Laure

    Dans le but d'utiliser un radar comme instrument de mesures oceanographiques, il apparai t necessaire de developper des techniques pour extraire les caracteristiques d'une surface de mer a partir du signal recu par le radar. La plupart des algorithmes existant considerent les images radar comme des photographies de la surface oceanique, negligeant l'effet de la vitesse de rotation du radar sur le signal, ainsi que le systeme de coordonnees polaires intrinseque de l'image radar. De plus, a cause de la loudeur des calculs, ces methodes ne peuvent fournir de resultats dans des applications en temps reel. La premiere partie de notra travail consiste a modeliser et quantifier l'effet de la distorsion du spectre oceanique provoquee par une vitesse de rotation du radar trop faible. Les resultats permettent de definir clairement les vitesses de rotation du radar pour lesquelles cette distorsion est negligeable. La deuxieme partie prospose un algorithme de traitement en temps reel qui extrait les informations caracteristiques principales de la surface de mer observee, i.e., la longueur d'onde et la direction des vagues. Cette estimation, basees sur une modelisation autoregressive offre une ouverture pour le traitement des signaux en temps reel. A travers cette approche, une succession de signaux unidimensionnels est traitee, ce qui conduit a l'elimination naturelle de la distorsion introduite dans le spectre du signal.

  5. Isolation of ZnO-binding 12-mer peptides and determination of their binding epitopes by NMR spectroscopy.

    PubMed

    Rothenstein, Dirk; Claasen, Birgit; Omiecienski, Beatrice; Lammel, Patricia; Bill, Joachim

    2012-08-01

    Inorganic-binding peptides are in the focus of research fields such as materials science, nanotechnology, and biotechnology. Applications concern surface functionalization by the specific coupling to inorganic target substrates, the binding of soluble molecules for sensing applications, or biomineralization approaches for the controlled formation of inorganic materials. The specific molecular recognition of inorganic surfaces by peptides is of major importance for such applications. Zinc oxide (ZnO) is an important semiconductor material which is applied in various devices. In this study the molecular fundamentals for a ZnO-binding epitope was determined. 12-mer peptides, which specifically bind to the zinc- or/and the oxygen-terminated sides of single-crystalline ZnO (0001) and (000-1) substrates, were selected from a random peptide library using the phage display technique. For two ZnO-binding peptides the mandatory amino acid residues, which are of crucial importance for the specific binding were determined with a label-free nuclear magnetic resonance (NMR) approach. NMR spectroscopy allows the identification of pH dependent interaction sites on the atomic level of 12-mer peptides and ZnO nanoparticles. Here, ionic and polar interaction forces were determined. For the oxygen-terminated side the consensus peptide-binding sequence (HSXXH) was predicted in silico and confirmed by the NMR approach. PMID:22720657

  6. Receptor Tyrosine Kinases, TYRO3, AXL, and MER, Demonstrate Distinct Patterns and Complex Regulation of Ligand-induced Activation*

    PubMed Central

    Tsou, Wen-I; Nguyen, Khanh-Quynh N.; Calarese, Daniel A.; Garforth, Scott J.; Antes, Anita L.; Smirnov, Sergey V.; Almo, Steve C.; Birge, Raymond B.; Kotenko, Sergei V.

    2014-01-01

    TYRO3, AXL, and MER receptors (TAMs) are three homologous type I receptor-tyrosine kinases that are activated by endogenous ligands, protein S (PROS1) and growth arrest-specific gene 6 (GAS6). These ligands can either activate TAMs as soluble factors, or, in turn, opsonize phosphatidylserine (PS) on apoptotic cells (ACs) and serve as bridging molecules between ACs and TAMs. Abnormal expression and activation of TAMs have been implicated in promoting proliferation and survival of cancer cells, as well as in suppressing anti-tumor immunity. Despite the fact that TAM receptors share significant similarity, little is known about the specificity of interaction between TAM receptors and their ligands, particularly in the context of ACs, and about the functional diversity of TAM receptors. To study ligand-mediated activation of TAMs, we generated a series of reporter cell lines expressing chimeric TAM receptors. Using this system, we found that each TAM receptor has a unique pattern of interaction with and activation by GAS6 and PROS1, which is also differentially affected by the presence of ACs, PS-containing lipid vesicles and enveloped virus. We also demonstrated that γ-carboxylation of ligands is essential for the full activation of TAMs and that soluble immunoglobulin-like TAM domains act as specific ligand antagonists. These studies demonstrate that, despite their similarity, TYRO3, AXL, and MER are likely to perform distinct functions in both immunoregulation and the recognition and removal of ACs. PMID:25074926

  7. Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks

    PubMed Central

    2013-01-01

    Background As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. Methods Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. Results The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. Conclusions These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities. PMID:24359669

  8. Evolution of hut access facing glacier shrinkage in the Mer de Glace basin (Mont Blanc massif, France)

    NASA Astrophysics Data System (ADS)

    Mourey, Jacques; Ravanel, Ludovic

    2016-04-01

    Given the evolution of high mountain environment due to global warming, mountaineering routes and huts accesses are more and more strongly affected by glacial shrinkage and concomitant gravity processes, but almost no studies have been conducted on this relationship. The aim of this research is to describe and explain the evolution over the last century of the access to the five alpine huts around the Mer de Glace glacier (Mont Blanc massif), the larger French glacier (length = 11.5 km, area = 30 km²), a major place for Alpine tourism since 1741 and the birthplace of mountaineering, by using several methods (comparing photographs, surveying, collecting historical documents). While most of the 20th century shows no marked changes, loss of ice thickness and associated erosion of lateral moraines generate numerous and significant changes since the 1990s. Boulder falls, rockfalls and landslides are the main geomorphological processes that affect the access, while the glacier surface lowering makes access much longer and more unstable. The danger is then greatly increased and the access must be relocated and/or equipped more and more frequently (e.g. a total of 520 m of ladders has been added). This questions the future accessibility to the huts, jeopardizing an important part of mountaineering and its linked economy in the Mer de Glace area.

  9. Comparing the Chemistry for the Pathfinder, MER and MSL Martian Landing Sites with APXS

    NASA Astrophysics Data System (ADS)

    Gellert, R.; Arvidson, R. E.; Clark, B. C.; Grotzinger, J. P.; Squyres, S. W.; Yen, A. S.

    2013-12-01

    The Alpha-Particle-X-ray Spectrometer is part of the science payload of all recent NASA Mars rover missions. It allows detailed comparison of the chemical composition and overall findings from rocks and soils at 4 landing sites. It can be even extended to the soil measurements performed with XRF on the two Viking landers. Typical soils at all 6 landing sites are very similar in chemical composition as well as mineralogy from instruments like Moessbauer on MER and CHEMIN on MSL. Beside a dominant basaltic composition the soil contains a significant altered and volatile rich component that is characterized by a constant S/Cl ratio in the APXS data. The overall similarity of the soils as well as the finding that soils around the 30 wt % SO3 rich bedrocks at Meridiani are not elevated in S, indicates the presence of a global distributed or at least large scale homogenized component in the Martian soil. This allows extending the SAM and CHEMIN findings in the altered and volatile components in the Gale Rocknest soils to other landing sites. However, in Gusev Crater anomalous subsurface soils were found - silica and hydrated ferric sulfate rich - that could indicate local fumarole and leaching activities. The sulfate rich Meridiani bedrock, called Burns formations, was documented to be remarkably homogeneous over the ~ 15 miles from the landing site at Eagle Crater to the base of the rim at Endurance Crater. Here for the first time a rover entered an area where evidence for clays is given by orbital CRISM data. With Opportunity's mineralogy instruments out of commission, the APXS was used to document the chemistry of the encountered outcrops. Having a composition close to the average Mars, one main characteristic feature of rocks at the rim is the low sulfur content compared to the younger Meridiani bedrock. The outcrops show post depositional cracks and veins filled with Calciumsulfate and Chlorine rich surface alteration rinds. A smaller outcrop called Esperance has

  10. Iron Mineralogy and Aqueous Alteration on Mars from the MER Moessbauer Spectrometers. Chapter 15

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Klingelhoefer, Goestar

    2007-01-01

    .05), is relatively uncommon, and occurs as subsurface deposits in the Columbia Hills. Berry Class soil is also heavily altered (SO3 = 5 +/- 1 wt.% and Fe(3+)/Fe(sub T) = 0.60 +/- 0.13) and occurs at Meridiani Planum as lag deposits, at the crests of aeolian bedforms, and as isolated pockets on outcrop surfaces. Magnetite is identified as the strongly magnetic component in martian soil. Jarosite (in the Burns outcrop at Meridiani Planum) and goethite (in Clovis Class rocks at Gusev crater) are mineralogical markers for aqueous processes because they contain the hydroxide anion (OH(-)) as an essential part of their structure. Each yields approx.10 wt.% H2O upon dehydroxylation. The presence of Fe sulfates on opposite sides of Mars is evidence that aqueous processes under acid sulfate conditions are or were common. Except for Independence Class rocks in the Columbia Hills, the overall Fe mineralogical compositions and similar basaltic bulk chemical compositions (calculated with respect to S = Cl = 0) of the population of altered rocks analyzed by MER imply isochemical alteration of basaltic precursors at low water-to-rock ratios.

  11. Geology and MER target site characteristics along the southern rim of Isidis Planitia, Mars

    USGS Publications Warehouse

    Crumpler, L.S.; Tanaka, K.L.

    2003-01-01

    crustal materials, in the form of rocks within the debris fans, and the weathered condition of the rocky material are potential sources for mineralogical evidence of climatic conditions in earliest Martian geologic history. The absence of alteration within rocks would, on the other hand, support the hypothesis that fluvial runoff during the earliest history of Mars was geologically brief rather than long-term and that long-term saturated groundwater flow was not present. Determination of the presence or absence of alteration would have corresponding implications for hypotheses requiring the long-term presence of aqueous solutions (i.e., complex organic compounds and life). A proposed MER site along the margin addresses realistic field science objectives of the Mars Exploration Rover mission and the current goals of the Mars Exploration Program. In situ measurements may be important in deriving estimates of the longevity and intensity of past wetter climates. Copyright 2003 by the American Geophysical Union.

  12. Paleomagnetic Evidence for the Tectono-Stratigraphic Evolution of the Mt.Galili Area / MER / Ethiopia

    NASA Astrophysics Data System (ADS)

    Popp, F.; Scholger, R.

    2007-12-01

    The Mt.Galili area (N 9,77°, E 040,55°) is the focus of current anthropological studies on early hominid evolution *[4]. The Mount Galili Formation (MGF)*[5] is subdivided into seven Members, each representing a sedimentary cycle, sustaining temporally interruptions by volcanic activity. Our paleomagnetic investigation concentrates on ascertaining primary magnetisation vectors (PMV) of volcanic layers embodied within the MGF, applying alternating field and thermal magnetic cleaning methods. Magnetite and ti-magnetite are the main carriers of the NRM (basalt, ignimbrite). Hematite shares in amounts up to 20%, Goethite occasionally participates up to 30% in magnitude of the NRM components. Two events of magnetic polarity reversals terminate a magnetic inverse period designating the lot of the MGF unit. The amount of the PMV's rotation in respect to an expected paleodirection*[1] of 183°/-13° are in the range of 1°-52° . The resulting mean PMV data provide implications on (A) rift-related block rotation / tilting in relation to the stable African crust since the Pliocene and they also support (B) stratigraphic age determinations of the MGF: A: Rotational movements cluster in 4 sectors: (a) The SE sector demonstrates almost unchanged orientation of the PMVs whereas (b) it's continuation to the NW sector suffered clockwise rotational tilting (up to 12° rot / 19° tilt). (c) The SW sector (Mt.Galili area s.str.) in contrast embrace a unique counterclockwise rotation component of 7°-17°, but the modulus of vector inclination, concerning individual rift blocks, is variable in either direction. (d) The NE sector (Satkawini) sustained the major counterclockwise rotation (41°°-52° rot / 3°- 17° tilt) We consider the Mt.Galili area being the place where trans-tensional tectonics were active during the late Miocene to create the lateral off-set of magmatic segments marking the centre of the MER. This tectonics are considered to belong to a arcuate accommodation

  13. Successful Mars remote sensors, MO THEMIS and MER Mini-TES

    NASA Astrophysics Data System (ADS)

    Silverman, Steven; Christensen, Phil

    2003-11-01

    Fourier Transform Spectrometer (FTS), covering the spectral range 5-29 μm at 10 cm-1 spectral resolution. Launched in June 2003, one Mini-TES instrument will fly to Mars aboard each of the two missions of NASA's Mars Exploration Rover Project (MER), named Spirit and Opportunity. The first Mini-TES unit was required to meet a two-year development schedule with proven, flight-tested instrumentation. Therefore, SBRS designed Mini-TES based on proven heritage from the successful MGS TES. THEMIS is based on "bolt-together" pushbroom optics and uncooled silicon microbolometer focal plane array (FPA) technology. Sometimes dubbed "Mars Landsat," THEMIS was launched in 2001 on Mars Odyssey, and provides guidance for future lander missions now in preparation for launch. Advanced materials and optical machining allow THEMIS low-scatter, reflective, wide field-of-view (WFOV) pushbroom optics for relatively long dwell-time compared to narrow FOV optics requiring cross-track scanning for equivalent spatial resolution. This allows uncooled silicon microbolometer FPAs, with less signal sensitivity than cryogenically cooled photo-diode FPAs, to meet the THEMIS sensitivity requirements. Instrument design, performance, integration, as well as details of the calibration are discussed. Full instrument and calibration details are available in the Journal of Geophysical Research Mini-TES and THEMIS papers by Christensen, et al.

  14. Seasonal variation of Argon in the martian atmosphere as measured by Spirit and Opportunity MER rovers

    NASA Astrophysics Data System (ADS)

    Economou, Thanasis

    Although there were no meteorological devices on any of the 2 rovers of the MER mission, by using the excellent ability of the Alpha Particle X-ray Spectrometer (APXS) to detect even a small amount of the Ar gas in a predominantly CO2 martian atmosphere, we were able to obtain detailed information on the variability of the atmospheric Ar as a function of seasonal changes. The technique is simple and straightforward. In order to increase the accuracy of the technique by eliminating any interference from target elements and minimizing the background from the backscattered Pu-L X-ray lines, dedicated APXS atmospheric Ar measurements were performed over a period of almost 4 martian years. In that mode the only visible peak in the x-ray spectra is the Ar Kα x-ray line at energy Eα=2.96 keV. Polar condensation of CO2 during winter periods, when the temperature falls below the freezing point of CO2, causes massive movement of air masses from the equatorial regions towards the poles. As the CO2 freezes, the remaining air there is enriched in argon (and nitrogen). The GRS experiment on the Odyssey orbiter around Mars has observed a six-fold in the Ar/CO2 mixing ratio in the southern polar region during the winter period. During the summer season, the opposite occurs: sublimating CO2 increases the atmospheric pressure and creates an atmospheric high that pushes the air mass with an enriched Ar fraction towards the equatorial regions where when arrives it is detected by the APXS on the Opportunity and Spirit landing sites. Our results indicate that the variation of the Ar in the martian atmosphere at both landing sites follows generally the variation of the atmospheric pressure, but it is not in phase with it: there is a phase shift of almost one martian season. The measurement of the Ar mixing ratio at the Spirit and Opportunity landing sites is thus a direct probe of the global circulation between the polar CO2 resource/sink and the equatorial regions. This information is

  15. Regulation of placental low-density lipoprotein uptake in baboons by estrogen: Dose-dependent effects of the anti-estrogen ethamoxytriphetol (MER-25)

    SciTech Connect

    Henson, M.C.; Pepe, G.J.; Albrecht, E.D. )

    1991-07-01

    In the present study, increasing amounts of the anti-estrogen 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenoletha nol (MER-25) were administered to pregnant baboons (Papio anubis) to block the action of endogenous estrogen and to determine effect on placental low-density lipoprotein (LDL) uptake. Pregnant baboons were untreated (n = 8) or received MER-25 orally at a dosage of 25 (n = 10), 50 (n = 8), or 75 (n = 4) mg/kg BW daily on Days 140-170 of gestation (term = 184 days). Placentas were removed on Day 170 of gestation and villous tissue was dispersed with 0.1% collagenase. Placental cells were incubated in Medium 199 for 12 h at 37{degrees} C with increasing amounts of 125I-LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean ({plus minus} SEM) placental uptake (ng/micrograms cell protein) of 125I-LDL was 55% (6.4 {plus minus} 1.0), 75% (3.6 {plus minus} 0.7), and 81% (2.7 {plus minus} 0.2) lower (p less than 0.001) in baboons that received MER-25 in doses of 25, 50, and 75 mg/kg BW, respectively, than in untreated baboons (14.2 {plus minus} 1.3 ng/micrograms cell protein). Maximal effect occurred with 50 mg MER-25, because LDL uptake was not further decreased with greater levels of MER-25. Dissociation constants for placental LDL uptake, as determined by Scatchard analysis, were unaltered by anti-estrogen treatment. The amount of 125I-LDL degradation by placental cells of untreated and MER-25-treated baboons was proportional to LDL uptake.

  16. CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection

    PubMed Central

    Caì, Yíngyún; Yú, Shuǐqìng; Postnikova, Elena N.; Mazur, Steven; Bernbaum, John G.; Burk, Robin; Zhāng, Téngfēi; Radoshitzky, Sheli R.; Müller, Marcel A.; Jordan, Ingo; Bollinger, Laura; Hensley, Lisa E.; Jahrling, Peter B.; Kuhn, Jens H.

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. PMID:25409519

  17. A Single Serine Residue Determines Selectivity to Monovalent Metal Ions in Metalloregulators of the MerR Family

    PubMed Central

    Ibáñez, María M.

    2015-01-01

    ABSTRACT MerR metalloregulators alleviate toxicity caused by an excess of metal ions, such as copper, zinc, mercury, lead, cadmium, silver, or gold, by triggering the expression of specific efflux or detoxification systems upon metal detection. The sensor protein binds the inducer metal ion by using two conserved cysteine residues at the C-terminal metal-binding loop (MBL). Divalent metal ion sensors, such as MerR and ZntR, require a third cysteine residue, located at the beginning of the dimerization (α5) helix, for metal coordination, while monovalent metal ion sensors, such as CueR and GolS, have a serine residue at this position. This serine residue was proposed to provide hydrophobic and steric restrictions to privilege the binding of monovalent metal ions. Here we show that the presence of alanine at this position does not modify the activation pattern of monovalent metal sensors. In contrast, GolS or CueR mutant sensors with a substitution of cysteine for the serine residue respond to monovalent metal ions or Hg(II) with high sensitivities. Furthermore, in a mutant deleted of the Zn(II) exporter ZntA, they also trigger the expression of their target genes in response to either Zn(II), Cd(II), Pb(II), or Co(II). IMPORTANCE Specificity in a stressor's recognition is essential for mounting an appropriate response. MerR metalloregulators trigger the expression of specific resistance systems upon detection of heavy metal ions. Two groups of these metalloregulators can be distinguished, recognizing either +1 or +2 metal ions, depending on the presence of a conserved serine in the former or a cysteine in the latter. Here we demonstrate that the serine residue in monovalent metal ion sensors excludes divalent metal ion detection, as its replacement by cysteine renders a pan-metal ion sensor. Our results indicate that the spectrum of signals detected by these sensors is determined not only by the metal-binding ligand availability but also by the metal-binding cavity

  18. Toward Developing a Preventive MERS-CoV Vaccine—Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14–15, 2015

    PubMed Central

    Delvecchio, Christopher J.; Wiley, Ryan E.; Williams, Marni; Yoon, In-Kyu; Modjarrad, Kayvon; Boujelal, Mohamed; Moorthy, Vasee S.; Hersi, Ahmad Salah; Kim, Jerome H.

    2016-01-01

    Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14–15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed. PMID:27439020

  19. Toward Developing a Preventive MERS-CoV Vaccine-Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14-15, 2015.

    PubMed

    Excler, Jean-Louis; Delvecchio, Christopher J; Wiley, Ryan E; Williams, Marni; Yoon, In-Kyu; Modjarrad, Kayvon; Boujelal, Mohamed; Moorthy, Vasee S; Hersi, Ahmad Salah; Kim, Jerome H

    2016-08-01

    Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14-15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed.

  20. Toward Developing a Preventive MERS-CoV Vaccine-Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14-15, 2015.

    PubMed

    Excler, Jean-Louis; Delvecchio, Christopher J; Wiley, Ryan E; Williams, Marni; Yoon, In-Kyu; Modjarrad, Kayvon; Boujelal, Mohamed; Moorthy, Vasee S; Hersi, Ahmad Salah; Kim, Jerome H

    2016-08-01

    Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14-15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed. PMID:27439020

  1. Successful Mars remote sensors, MO THEMIS and MER Mini-TES

    NASA Astrophysics Data System (ADS)

    Silverman, Steven; Christensen, Phil

    2006-10-01

    spectral range 5 29μm at 10cm spectral resolution. Launched in June 2003, one Mini-TES instrument will fly to Mars aboard each of the two missions of NASA's Mars Exploration Rover Project (MER), named Spirit and Opportunity. The first Mini-TES unit was required to meet a two-year development schedule with proven, flight-tested instrumentation. Therefore, SBRS designed Mini-TES based on proven heritage from the successful MGS TES. THEMIS is based on “bolt-together” pushbroom optics and uncooled silicon microbolometer focal plane array (FPA) technology. Sometimes dubbed “Mars Landsat,” THEMIS was launched in 2001 on Mars Odyssey, and provides guidance for future lander missions now in preparation for launch. Advanced materials and optical machining allow THEMIS low-scatter, reflective, wide field-of-view (WFOV) pushbroom optics for relatively long dwell-time compared to narrow FOV optics requiring cross-track scanning for equivalent spatial resolution. This allows uncooled silicon microbolometer FPAs, with less signal sensitivity than cryogenically cooled photo-diode FPAs, to meet the THEMIS sensitivity requirements. Instrument design, performance, integration, as well as details of the calibration are discussed. Full instrument and calibration details are available in the Journal of Geophysical Research Mini-TES and THEMIS papers by Christensen et al.

  2. Association of Higher MERS-CoV Virus Load with Severe Disease and Death, Saudi Arabia, 2014.

    PubMed

    Feikin, Daniel R; Alraddadi, Basem; Qutub, Mohammed; Shabouni, Omaima; Curns, Aaron; Oboho, Ikwo K; Tomczyk, Sara M; Wolff, Bernard; Watson, John T; Madani, Tariq A

    2015-11-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of illness. We evaluated whether cycle threshold (Ct) values (which are inversely related to virus load) were associated with clinical severity in patients from Saudi Arabia whose nasopharyngeal specimens tested positive for this virus by real-time reverse transcription PCR. Among 102 patients, median Ct of 31.0 for the upstream of the E gene target for 41 (40%) patients who died was significantly lower than the median of 33.0 for 61 survivors (p=0.0087). In multivariable regression analyses, risk factors for death were age>60 years), underlying illness, and decreasing Ct for each 1-point decrease in Ct). Results were similar for a composite severe outcome (death and/or intensive care unit admission). More data are needed to determine whether modulation of virus load by therapeutic agents affects clinical outcomes. PMID:26488195

  3. The Martian Soil as a Geochemical Sink for Hydrothermally Altered Crustal Rocks and Mobile Elements: Implications of Early MER Results

    NASA Technical Reports Server (NTRS)

    Newsom, H. E.; Nelson, M. J.; Shearer, C. K.; Draper, D. S.

    2005-01-01

    Hydrothermal and aqueous alteration can explain some of the exciting results from the MER team s analyses of the martian soil, including the major elements, mobile elements, and the nickel enrichment. Published results from the five lander missions lead to the following conclusions: 1) The soil appears to be globally mixed and basaltic with only small local variations in chemistry. Relative to martian basaltic meteorites and Gusev rocks the soils are depleted in the fluid-mobile element calcium, but only slightly enriched to somewhat depleted in iron oxide. 2) The presence of olivine in the soils based on M ssbauer data argues that the soil is only partly weathered and is more akin to a lunar regolith than a terrestrial soil. 3) The presence of bromine along with sulfur and chlorine in the soils is consistent with addition of a mobile element component to the soil.

  4. A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma

    SciTech Connect

    O'Connel, M.J.; Childs, D.S.; Moertel, C.G.; Holbrook, M.A.; Schutt, A.J.; Rubin, J.; Ritts, R.E. Jr.

    1982-07-01

    Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression.Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.

  5. Mercury (II) sensor based on monitoring dissociation rate of the trans-acting factor MerR from cis-element by surface plasmon resonance.

    PubMed

    Taniguchi, Masaki; Siddiki, Mohammad Shohel Rana; Ueda, Shunsaku; Maeda, Isamu

    2015-05-15

    Transcriptional switches regulate gene expression in response to environmental changes surrounding cell. Many studies have focused on two fundamentally different models of transcriptional control by bacterial metalloregulatory protein. Distortion of the DNA fragment including cis-element, to which the trans-acting factor MerR binds, is accepted as the mechanism of gene expression regulation by Hg (II) while, in cases of the other trans-acting factors ArsR and CadC, events of association to and dissociation from cis-element are known to control transcription in response to As (III) and Cd (II), respectively. In this study, interactions between green-fluorescent-protein-tagged trans-acting factor and immobilized cis-element were analyzed on solid surface. Fluorescent measurements and surface plasmon resonance (SPR) responses revealed that although the equilibrium dissociation constant (KD) was much lower in MerR than in ArsR and CadC, the dissociation rate of MerR from DNA increased in response to Hg (II) at concentrations of 5-10(4) µg l(-1). These results firstly demonstrate an increase of KD between MerR and its recognition site in DNA by Hg (II), and possibility of rapid Hg (II) quantification with the low detection limit (5 µg l(-1)) and the high dynamic range (10(1)-10(4) µg l(-1)).

  6. Working on Mars: Understanding How Scientists, Engineers and Rovers Interacted Across Space and Time during the Mars Exploration Rover (MER) Mission

    NASA Technical Reports Server (NTRS)

    Wales, Roxana C.

    2005-01-01

    This viewgraph presentation summarizes the scheduling and planning difficulties inherent in operating the Mars Exploration Rovers (MER) during the overlapping terrestrial day and Martian sol. The presentation gives special empahsis to communication between the teams controlling the rovers from Earth, and keeping track of time on the two planets.

  7. Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

    PubMed Central

    Kim, Si-Yoon; Lim, Eun-Jin; Yoon, Young-So; Ahn, Young-Ho; Park, Eun-Mi; Kim, Hee-Sun; Kang, Jihee Lee

    2016-01-01

    Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXRα and LXRβ and expression of their target genes were inhibited in BMDM from STAT1−/− mice or by the STAT1-specific inhibitor fludarabine. Gas6-induced STAT1 phosphorylation, LXR activation, and LXR target gene expression were inhibited in BMDM from Mer−/− mice or by inhibition of PI3K or Akt. Gas6-induced Akt phosphorylation was inhibited in BMDM from STAT1−/− mice or in the presence of fludarabine. Gas6-induced LXR activity was enhanced through an interaction between LXRα and STAT1 on the DNA promoter of Arg2. Additionally, we found that Gas6 inhibited lipopolysaccharide (LPS)-induced nitrite production in a STAT1 and LXR pathway-dependent manner in BMDM. Additionally, Mer-neutralizing antibody reduced LXR and Arg2 expression in lung tissue and enhanced NO production in bronchoalveolar lavage fluid in LPS-induced acute lung injury. Our data suggest the possibility that the Gas6-Mer-PI3K/Akt-STAT1-LXR-Arg2 pathway plays an essential role for resolving inflammatory response in acute lung injury. PMID:27406916

  8. Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

    PubMed Central

    Bhadra, Sanchita; Jiang, Yu Sherry; Kumar, Mia R.; Johnson, Reed F.; Hensley, Lisa E.; Ellington, Andrew D.

    2015-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens. PMID:25856093

  9. Professional Organizations and the Professionalizing of Practice: The Role of MER, EdCom, and the NAEA Museum Education Division, 1969-2002

    ERIC Educational Resources Information Center

    Kai-Kee, Elliott

    2012-01-01

    The establishment of the Museum Education Roundtable (MER) in 1969, the formation of the Committee on Education of the American Association of Museums (AAM) in 1973, and the creation of the Museum Education Division of the National Art Education Association (NAEA) in 1981 all represent milestones in the professionalization of museum education…

  10. High-resolution topomapping of candidate MER landing sites with Mars Orbiter Camera narrow-angle images

    USGS Publications Warehouse

    Kirk, R.L.; Howington-Kraus, E.; Redding, B.; Galuszka, D.; Hare, T.M.; Archinal, B.A.; Soderblom, L.A.; Barrett, J.M.

    2003-01-01

    We analyzed narrow-angle Mars Orbiter Camera (MOC-NA) images to produce high-resolution digital elevation models (DEMs) in order to provide topographic and slope information needed to assess the safety of candidate landing sites for the Mars Exploration Rovers (MER) and to assess the accuracy of our results by a variety of tests. The mapping techniques developed also support geoscientific studies and can be used with all present and planned Mars-orbiting scanner cameras. Photogrammetric analysis of MOC stereopairs yields DEMs with 3-pixel (typically 10 m) horizontal resolution, vertical precision consistent with ???0.22 pixel matching errors (typically a few meters), and slope errors of 1-3??. These DEMs are controlled to the Mars Orbiter Laser Altimeter (MOLA) global data set and consistent with it at the limits of resolution. Photoclinometry yields DEMs with single-pixel (typically ???3 m) horizontal resolution and submeter vertical precision. Where the surface albedo is uniform, the dominant error is 10-20% relative uncertainty in the amplitude of topography and slopes after "calibrating" photoclinometry against a stereo DEM to account for the influence of atmospheric haze. We mapped portions of seven candidate MER sites and the Mars Pathfinder site. Safety of the final four sites (Elysium, Gusev, Isidis, and Meridiani) was assessed by mission engineers by simulating landings on our DEMs of "hazard units" mapped in the sites, with results weighted by the probability of landing on those units; summary slope statistics show that most hazard units are smooth, with only small areas of etched terrain in Gusev crater posing a slope hazard.

  11. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.

    PubMed

    Bialek, Stephanie R; Allen, Donna; Alvarado-Ramy, Francisco; Arthur, Ray; Balajee, Arunmozhi; Bell, David; Best, Susan; Blackmore, Carina; Breakwell, Lucy; Cannons, Andrew; Brown, Clive; Cetron, Martin; Chea, Nora; Chommanard, Christina; Cohen, Nicole; Conover, Craig; Crespo, Antonio; Creviston, Jeanean; Curns, Aaron T; Dahl, Rebecca; Dearth, Stephanie; DeMaria, Alfred; Echols, Fred; Erdman, Dean D; Feikin, Daniel; Frias, Mabel; Gerber, Susan I; Gulati, Reena; Hale, Christa; Haynes, Lia M; Heberlein-Larson, Lea; Holton, Kelly; Ijaz, Kashef; Kapoor, Minal; Kohl, Katrin; Kuhar, David T; Kumar, Alan M; Kundich, Marianne; Lippold, Susan; Liu, Lixia; Lovchik, Judith C; Madoff, Larry; Martell, Sandra; Matthews, Sarah; Moore, Jessica; Murray, Linda R; Onofrey, Shauna; Pallansch, Mark A; Pesik, Nicki; Pham, Huong; Pillai, Satish; Pontones, Pam; Pringle, Kimberly; Pritchard, Scott; Rasmussen, Sonja; Richards, Shawn; Sandoval, Michelle; Schneider, Eileen; Schuchat, Anne; Sheedy, Kristine; Sherin, Kevin; Swerdlow, David L; Tappero, Jordan W; Vernon, Michael O; Watkins, Sharon; Watson, John

    2014-05-16

    Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.

  12. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.

    PubMed

    Bialek, Stephanie R; Allen, Donna; Alvarado-Ramy, Francisco; Arthur, Ray; Balajee, Arunmozhi; Bell, David; Best, Susan; Blackmore, Carina; Breakwell, Lucy; Cannons, Andrew; Brown, Clive; Cetron, Martin; Chea, Nora; Chommanard, Christina; Cohen, Nicole; Conover, Craig; Crespo, Antonio; Creviston, Jeanean; Curns, Aaron T; Dahl, Rebecca; Dearth, Stephanie; DeMaria, Alfred; Echols, Fred; Erdman, Dean D; Feikin, Daniel; Frias, Mabel; Gerber, Susan I; Gulati, Reena; Hale, Christa; Haynes, Lia M; Heberlein-Larson, Lea; Holton, Kelly; Ijaz, Kashef; Kapoor, Minal; Kohl, Katrin; Kuhar, David T; Kumar, Alan M; Kundich, Marianne; Lippold, Susan; Liu, Lixia; Lovchik, Judith C; Madoff, Larry; Martell, Sandra; Matthews, Sarah; Moore, Jessica; Murray, Linda R; Onofrey, Shauna; Pallansch, Mark A; Pesik, Nicki; Pham, Huong; Pillai, Satish; Pontones, Pam; Pringle, Kimberly; Pritchard, Scott; Rasmussen, Sonja; Richards, Shawn; Sandoval, Michelle; Schneider, Eileen; Schuchat, Anne; Sheedy, Kristine; Sherin, Kevin; Swerdlow, David L; Tappero, Jordan W; Vernon, Michael O; Watkins, Sharon; Watson, John

    2014-05-16

    Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014. PMID:24827411

  13. Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV

    PubMed Central

    ali, Mohammad Tuhin; Morshed, Mohammed Monzur; Gazi, Md. Amran; Musa, Md. Abu; Kibria, Md Golam; Uddin, Md Jashim; Khan, Md. Anik Ashfaq; Hasan, Shihab

    2014-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC50 value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule. PMID:25258490

  14. Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association

    SciTech Connect

    Jackson, D.V.; Paschal, B.R.; Ferree, C.

    1982-07-01

    The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (p > 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

  15. Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes.

    PubMed

    Atzin-Méndez, J A; López-González, J S; Báez, R; Arenas-Del Angel, M C; Montaño, L F; Silva-Adaya, D; Lascurain, R; Gorocica, P

    2016-01-01

    Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy.

  16. Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes

    PubMed Central

    ATZIN-MÉNDEZ, J.A.; LÓPEZ-GONZÁLEZ, J.S.; BÁEZ, R.; ARENAS-DEL ANGEL, M.C.; MONTAÑO, L.F.; SILVA-ADAYA, D.; LASCURAIN, R.; GOROCICA, P.

    2016-01-01

    Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy. PMID:26498650

  17. The Same Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) yet Different Outbreak Patterns and Public Health Impacts on the Far East Expert Opinion from the Rapid Response Team of the Republic of Korea.

    PubMed

    2015-12-01

    A Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) outbreak, the largest outbreak outside the Middle East in 2012, occurred in the Republic of Korea and resulted in a large number of cases, with 186 infected people, including 38 deaths. A Rapid Response Team (RRT) was appointed after a request from the Korean government on June 8, 2015 calling for specialists to manage and control the MERS-CoV outbreak. This report presents the opinion of the RRT who worked to manage this healthcare-associated MERS-CoV outbreak in Korea.

  18. The Same Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) yet Different Outbreak Patterns and Public Health Impacts on the Far East Expert Opinion from the Rapid Response Team of the Republic of Korea

    PubMed Central

    2015-01-01

    A Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) outbreak, the largest outbreak outside the Middle East in 2012, occurred in the Republic of Korea and resulted in a large number of cases, with 186 infected people, including 38 deaths. A Rapid Response Team (RRT) was appointed after a request from the Korean government on June 8, 2015 calling for specialists to manage and control the MERS-CoV outbreak. This report presents the opinion of the RRT who worked to manage this healthcare-associated MERS-CoV outbreak in Korea. PMID:26788408

  19. Discovery of Carbonate-Rich Outcrops in the Gusev Crater Columbia Hills by the MER Rover Spirit

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Ruff, Steven W.; Gellert, Ralf; Ming, Douglas W.; Arvidson, Raymond E.; Clark, Benton C.; Golden, Dadi C.; Siebach, Kirsten L.; Klingelhoefer, Goestar; Schroeder, Christian; Fleischer, Iris; Yen, Albert S.; Squyres, Steven W.

    2010-01-01

    The chemical composition, global abundance, distribution, and formation pathways of carbonates are central to understanding aqueous processes, climate, and habitability of early Mars. The Mars Exploration Rover (MER) Spirit analyzed a series of olivine-rich outcrops while descending from the summit region of Husband Hill into the Inner Basin of the Columbia Hills of Gusev Crater to the eastern edge of the El Dorado ripple field in late 2005. Reanalysis of Spirit s mineralogical data from the Moessbauer Spectrometer (MB) and the Miniature Thermal Emission Spectrometer (Mini-TES) and chemical data from the Alpha Particle X-Ray Spectrometer (APXS) in 2010, coupled with new laboratory data for carbonate-bearing samples, lead to identification of carbonate in one of the outcrops (Comanche) [Morris, R.V., et al., Science, 329, 421-424]. The carbonate is rich in magnesium and iron (Mc62Sd25Cc11Rh2, assuming all Ca and Mn is associated with the carbonate) and is a major component of the Comanche outcrops (16 to 34 wt.%). The mineralogical, chemical, and abundance data are constrained in multiple, mutually consistent ways by the MER analyses. For example, a low-Ca carbonate is required by the MB and APXS data and is consistent with Mini-TES data. Three spectral features attributable to fundamental infrared vibrational modes of low-Ca carbonate are present in the Mini-TES spectra of Comanche outcrops. The average composition of Comanche carbonate approximates the average composition of the carbonate globules in Martian meteorite ALH 84001. Analogy with ALH 84001, terrestrial, and synthetic carbonate globules suggests that Comanche carbonate precipitated from aqueous solutions under hydrothermal conditions at near neutral pH in association with volcanic activity during the Noachian era. Comanche outcrop morphology suggests they are remnants of a larger carbonate-bearing formation that evolved in ultramafic rock and then preferentially eroded by a combination of aeolian

  20. Discovery of Carbonate-Rich Outcrops in the Gusev Crater Columbia Hills by the MER Rover Spirit

    NASA Astrophysics Data System (ADS)

    Morris, R. V.; Ruff, S. W.; Gellert, R.; Ming, D. W.; Arvidson, R. E.; Clark, B. C.; Golden, D. C.; Siebach, K. L.; Klingelhoefer, G.; Schroeder, C.; Fleischer, I.; Yen, A. S.; Squyres, S. W.

    2010-12-01

    The chemical composition, global abundance, distribution, and formation pathways of carbonates are central to understanding aqueous processes, climate, and habitability of early Mars. The Mars Exploration Rover (MER) Spirit analyzed a series of olivine-rich outcrops while descending from the summit region of Husband Hill into the Inner Basin of the Columbia Hills of Gusev Crater to the eastern edge of the El Dorado ripple field in late 2005. Reanalysis of Spirit’s mineralogical data from the Moessbauer Spectrometer (MB) and the Miniature Thermal Emission Spectrometer (Mini-TES) and chemical data from the Alpha Particle X-Ray Spectrometer (APXS) in 2010, coupled with new laboratory data for carbonate-bearing samples, lead to identification of carbonate in one of the outcrops (Comanche) [Morris, R.V., et al., Science, 329, 421-424]. The carbonate is rich in magnesium and iron (Mc62Sd25Cc11Rh2, assuming all Ca and Mn is associated with the carbonate) and is a major component of the Comanche outcrops (16 to 34 wt.%). The mineralogical, chemical, and abundance data are constrained in multiple, mutually consistent ways by the MER analyses. For example, a low-Ca carbonate is required by the MB and APXS data and is consistent with Mini-TES data. Three spectral features attributable to fundamental infrared vibrational modes of low-Ca carbonate are present in the Mini-TES spectra of Comanche outcrops. The average composition of Comanche carbonate approximates the average composition of the carbonate globules in Martian meteorite ALH 84001. Analogy with ALH 84001, terrestrial, and synthetic carbonate globules suggests that Comanche carbonate precipitated from aqueous solutions under hydrothermal conditions at near neutral pH in association with volcanic activity during the Noachian era. Comanche outcrop morphology suggests they are remnants of a larger carbonate-bearing formation that evolved in ultramafic rock and then preferentially eroded by a combination of aeolian

  1. Apoptotic cell clearance of Leishmania major-infected neutrophils by dendritic cells inhibits CD8+ T-cell priming in vitro by Mer tyrosine kinase-dependent signaling

    PubMed Central

    Ribeiro-Gomes, F L; Romano, A; Lee, S; Roffê, E; Peters, N C; Debrabant, A; Sacks, D

    2015-01-01

    Neutrophils are the predominant recruited and infected cells during the early stages of Leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. In order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (DCs) in vitro. The capture of infected, apoptotic neutrophils by the DCs completely inhibited their cross-presentation function that was dependent on engagement of the receptor tyrosine kinase Mer on the DCs. The capture of uninfected neutrophils, or neutrophils infected with Toxoplasma gondii, had only slight immunomodulatory effects. These studies define the clearance of infected, apoptotic neutrophils by DCs and Mer receptor signaling as central to the early immune evasion strategies of L. major, with relevance to other vector-borne pathogens delivered by bite to the skin. PMID:26658192

  2. CDC's Early Response to a Novel Viral Disease, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), September 2012-May 2014.

    PubMed

    Williams, Holly Ann; Dunville, Richard L; Gerber, Susan I; Erdman, Dean D; Pesik, Nicki; Kuhar, David; Mason, Karen A; Haynes, Lia; Rotz, Lisa; St Pierre, Jeanette; Poser, Sarah; Bunga, Sudhir; Pallansch, Mark A; Swerdlow, David L

    2015-01-01

    The first ever case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported in September 2012. This report describes the approaches taken by CDC, in collaboration with the World Health Organization (WHO) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the United States in May 2014. During this time, CDC's response integrated multiple disciplines and was divided into three distinct phases: before, during, and after the initial activation of its Emergency Operations Center. CDC's response to MERS-CoV required a large effort, deploying at least 353 staff members who worked in the areas of surveillance, laboratory capacity, infection control guidance, and travelers' health. This response built on CDC's experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats.

  3. Expedient chemical synthesis of 75mer DNA binding domain of MafA: an insight on its binding to insulin enhancer.

    PubMed

    Pellegrino, Sara; Annoni, Chiara; Contini, Alessandro; Clerici, Francesca; Gelmi, Maria Luisa

    2012-11-01

    An expedient chemical synthesis of a 75mer peptide corresponding to the DNA binding domain (DBD, 227-301) of the human MafA leucine zipper transcription factor is reported. The application of microwave-assisted solid phase peptide synthesis (MW-SPPS) with a protocol modified respect to the standard one allowed obtaining the desired 75mer peptide in a short time with high quantity and optimal purity. MW-SPPS methodology was thus demonstrated as a valuable alternative to recombinant methods to obtain protein domains. Considering that recent findings suggest an involvement of MafA in the pathogenesis of diabetes mellitus, we also performed circular dichroism studies both on DBD folding and its interaction with MafA recognition element (MARE) on insulin enhancer. From our results, it was evicted that a disorder to order transition occurs after DBD interaction with insulin MARE which is mediated by specific structural elements on the N-terminus of the DBD.

  4. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection

    PubMed Central

    Pascal, Kristen E.; Coleman, Christopher M.; Mujica, Alejandro O.; Kamat, Vishal; Badithe, Ashok; Fairhurst, Jeanette; Hunt, Charleen; Strein, John; Berrebi, Alexander; Sisk, Jeanne M.; Matthews, Krystal L.; Babb, Robert; Chen, Gang; Lai, Ka-Man V.; Huang, Tammy T.; Olson, William; Yancopoulos, George D.; Stahl, Neil; Frieman, Matthew B.; Kyratsous, Christos A.

    2015-01-01

    Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics. PMID:26124093

  5. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

    PubMed

    Pascal, Kristen E; Coleman, Christopher M; Mujica, Alejandro O; Kamat, Vishal; Badithe, Ashok; Fairhurst, Jeanette; Hunt, Charleen; Strein, John; Berrebi, Alexander; Sisk, Jeanne M; Matthews, Krystal L; Babb, Robert; Chen, Gang; Lai, Ka-Man V; Huang, Tammy T; Olson, William; Yancopoulos, George D; Stahl, Neil; Frieman, Matthew B; Kyratsous, Christos A

    2015-07-14

    Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.

  6. CDC's Early Response to a Novel Viral Disease, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), September 2012–May 2014

    PubMed Central

    Dunville, Richard L.; Gerber, Susan I.; Erdman, Dean D.; Pesik, Nicki; Kuhar, David; Mason, Karen A.; Haynes, Lia; Rotz, Lisa; St. Pierre, Jeanette; Poser, Sarah; Bunga, Sudhir; Pallansch, Mark A.; Swerdlow, David L.

    2015-01-01

    The first ever case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported in September 2012. This report describes the approaches taken by CDC, in collaboration with the World Health Organization (WHO) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the United States in May 2014. During this time, CDC's response integrated multiple disciplines and was divided into three distinct phases: before, during, and after the initial activation of its Emergency Operations Center. CDC's response to MERS-CoV required a large effort, deploying at least 353 staff members who worked in the areas of surveillance, laboratory capacity, infection control guidance, and travelers' health. This response built on CDC's experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats. PMID:26345122

  7. Structural characterization of the N-terminal part of the MERS-CoV nucleocapsid by X-ray diffraction and small-angle X-ray scattering.

    PubMed

    Papageorgiou, Nicolas; Lichière, Julie; Baklouti, Amal; Ferron, François; Sévajol, Marion; Canard, Bruno; Coutard, Bruno

    2016-02-01

    The N protein of coronaviruses is a multifunctional protein that is organized into several domains. The N-terminal part is composed of an intrinsically disordered region (IDR) followed by a structured domain called the N-terminal domain (NTD). In this study, the structure determination of the N-terminal region of the MERS-CoV N protein via X-ray diffraction measurements is reported at a resolution of 2.4 Å. Since the first 30 amino acids were not resolved by X-ray diffraction, the structural study was completed by a SAXS experiment to propose a structural model including the IDR. This model presents the N-terminal region of the MERS-CoV as a monomer that displays structural features in common with other coronavirus NTDs. PMID:26894667

  8. Skip the Alignment: Degenerate, Multiplex Primer and Probe Design Using K-mer Matching Instead of Alignments

    PubMed Central

    Hysom, David A.; Naraghi-Arani, Pejman; Elsheikh, Maher; Carrillo, A. Celena; Williams, Peter L.; Gardner, Shea N.

    2012-01-01

    PriMux is a new software package for selecting multiplex compatible, degenerate primers and probes to detect diverse targets such as viruses. It requires no multiple sequence alignment, instead applying k-mer algorithms, hence it scales well for large target sets and saves user effort from curating sequences into alignable groups. PriMux has the capability to predict degenerate primers as well as probes suitable for TaqMan or other primer/probe triplet assay formats, or simply probes for microarray or other single-oligo assay formats. PriMux employs suffix array methods for efficient calculations on oligos 10-∼100 nt in length. TaqMan® primers and probes for each segment of Rift Valley fever virus were designed using PriMux, and lab testing comparing signatures designed using PriMux versus those designed using traditional methods demonstrated equivalent or better sensitivity for the PriMux-designed signatures compared to traditional signatures. In addition, we used PriMux to design TaqMan® primers and probes for unalignable or poorly alignable groups of targets: that is, all segments of Rift Valley fever virus analyzed as a single target set of 198 sequences, or all 2863 Dengue virus genomes for all four serotypes available at the time of our analysis. The PriMux software is available as open source from http://sourceforge.net/projects/PriMux. PMID:22485178

  9. Estimation of the Whitefly Bemisia tabaci Genome Size Based on k-mer and Flow Cytometric Analyses

    PubMed Central

    Chen, Wenbo; Hasegawa, Daniel K.; Arumuganathan, Kathiravetpillai; Simmons, Alvin M.; Wintermantel, William M.; Fei, Zhangjun; Ling, Kai-Shu

    2015-01-01

    Whiteflies of the Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic species complex are among the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 1000 species of plants worldwide and inflict severe economic losses to crops, mainly through the transmission of pathogenic viruses. Surprisingly, there is very little genomic information about whiteflies. As a starting point to genome sequencing, we report a new estimation of the genome size of the B. tabaci B biotype or Middle East-Asia Minor 1 (MEAM1) population. Using an isogenic whitefly colony with over 6500 haploid male individuals for genomic DNA, three paired-end genomic libraries with insert sizes of ~300 bp, 500 bp and 1 Kb were constructed and sequenced on an Illumina HiSeq 2500 system. A total of ~50 billion base pairs of sequences were obtained from each library. K-mer analysis using these sequences revealed that the genome size of the whitefly was ~682.3 Mb. In addition, the flow cytometric analysis estimated the haploid genome size of the whitefly to be ~690 Mb. Considering the congruency between both estimation methods, we predict the haploid genome size of B. tabaci MEAM1 to be ~680–690 Mb. Our data provide a baseline for ongoing efforts to assemble and annotate the B. tabaci genome. PMID:26463411

  10. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    PubMed

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

  11. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy

    PubMed Central

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research. PMID:26125617

  12. Estimation of the Whitefly Bemisia tabaci Genome Size Based on k-mer and Flow Cytometric Analyses.

    PubMed

    Chen, Wenbo; Hasegawa, Daniel K; Arumuganathan, Kathiravetpillai; Simmons, Alvin M; Wintermantel, William M; Fei, Zhangjun; Ling, Kai-Shu

    2015-01-01

    Whiteflies of the Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic species complex are among the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 1000 species of plants worldwide and inflict severe economic losses to crops, mainly through the transmission of pathogenic viruses. Surprisingly, there is very little genomic information about whiteflies. As a starting point to genome sequencing, we report a new estimation of the genome size of the B. tabaci B biotype or Middle East-Asia Minor 1 (MEAM1) population. Using an isogenic whitefly colony with over 6500 haploid male individuals for genomic DNA, three paired-end genomic libraries with insert sizes of ~300 bp, 500 bp and 1 Kb were constructed and sequenced on an Illumina HiSeq 2500 system. A total of ~50 billion base pairs of sequences were obtained from each library. K-mer analysis using these sequences revealed that the genome size of the whitefly was ~682.3 Mb. In addition, the flow cytometric analysis estimated the haploid genome size of the whitefly to be ~690 Mb. Considering the congruency between both estimation methods, we predict the haploid genome size of B. tabaci MEAM1 to be ~680-690 Mb. Our data provide a baseline for ongoing efforts to assemble and annotate the B. tabaci genome.

  13. Fractional statistical theory and use of quasi-chemical approximation for adsorption of interacting kk-mers

    NASA Astrophysics Data System (ADS)

    Dávila, M.; Riccardo, J. L.; Ramirez-Pastor, A. J.

    2009-02-01

    In a recent paper [J.L. Riccardo, A. J. Ramirez-Pastor, F. Romá, Phys. Rev. Lett. 94 (2004) 186101], a new fractional statistical theory of adsorption (FSTA) based on Haldane's statistics was presented. Later [M. Dávila, F. Romá, J.L. Riccardo, A.J. Ramirez-Pastor, Surf. Sci. 600 (2006) 2011], a generalization of the classical quasi-chemical approximation (QCA) was developed in which the adsorbate can occupy more than one adsorption site. In this paper, we describe the statistical thermodynamics of interacting polyatomic adsorbates ( k-mers) on homogeneous surfaces, by combining FSTA and QCA. The main thermodynamic functions are obtained in terms of two parameters, g and a, which are related directly to the spatial configuration of a polyatomic molecule in the adsorbed state. Analysis of simulated and experimental results have been carried out in order to (i) explore the reach and limitations of the theoretical model and (ii) evince the physical significance of g and a.

  14. Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates

    PubMed Central

    Gallo Cantafio, Maria Eugenia; Nielsen, Boye Schnack; Mignogna, Chiara; Arbitrio, Mariamena; Botta, Cirino; Frandsen, Niels M; Rolfo, Christian; Tagliaferri, Pierosandro; Tassone, Pierfrancesco; Di Martino, Maria Teresa

    2016-01-01

    Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer. PMID:27327137

  15. A First Look at the Mineralogy and Geochemistry of the MER-B Landing Site in Meridiani Planum

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Squyres, S.; Arvidson, R. E.; Bell, J. F., III; Christensen, P. C.; Gorevan, S.; Herkenhoff, K.; Klingelhoefer, G.; Rieder, R.; Farrand, W.

    2004-01-01

    The second MER rover (Opportunity) landed on Meridiani Planum on January 24, 2004 inside a shallow crater. The science rational for the selection of the landing site centered on detection of the mineral hematite from martian orbit by the Mars Global Surveyor Thermal Emission Spectrometer (MGS-TES) [1,2]. Other smaller occurrences of hematite are in Aram Chaos and several isolated spots in Valles Marineris. Proposed formation pathways for martian hematite include both aqueous (e.g., low temperature precipitation of Fe oxides/oxyhydroxides in a lacustrine environment, laterite-style weathering, and precipitation from fluids having a hydrothermal origin) and dry (e.g., oxidation of magnetite rich ash) processes [e.g., 1,2,3]. The crystallographic c-face of martian hematite must be exaggerated to account for the thermal emissions spectra and it must be gray in color so as to account for the absence of the characteristic spectral signature of red hematite at visible wavelengths

  16. Distortion of the Major Histocompatibility Complex Class I Binding Groove to Accommodate an Insulin-derived 10-Mer Peptide*

    PubMed Central

    Motozono, Chihiro; Pearson, James A.; De Leenheer, Evy; Rizkallah, Pierre J.; Beck, Konrad; Trimby, Andrew; Sewell, Andrew K.; Wong, F. Susan; Cole, David K.

    2015-01-01

    The non-obese diabetic mouse model of type 1 diabetes continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic β-cells. However, little is known about the molecular mechanisms that enable this disease pathway. We show that insulin reactivity by a CD8+ T-cell clone, known to induce type 1 diabetes, is characterized by weak T-cell antigen receptor binding to a relatively unstable peptide-MHC. The structure of the native 9- and 10-mer insulin epitopes demonstrated that peptide residues 7 and 8 form a prominent solvent-exposed bulge that could potentially be the main focus of T-cell receptor binding. The C terminus of the peptide governed peptide-MHC stability. Unexpectedly, we further demonstrate a novel mode of flexible peptide presentation in which the MHC peptide-binding groove is able to “open the back door” to accommodate extra C-terminal peptide residues. PMID:26085090

  17. Subunit sequences of the 4 x 6-mer hemocyanin from the golden orb-web spider, Nephila inaurata.

    PubMed

    Averdam, Anne; Markl, Jürgen; Burmester, Thorsten

    2003-08-01

    The transport of oxygen in the hemolymph of many arthropod and mollusc species is mediated by large copper-proteins that are referred to as hemocyanins. Arthropod hemocyanins are composed of hexamers and oligomers of hexamers. Arachnid hemocyanins usually form 4 x 6-mers consisting of seven distinct subunit types (termed a-g), although in some spider taxa deviations from this standard scheme have been observed. Applying immunological and electrophoretic methods, six distinct hemocyanin subunits were identified in the red-legged golden orb-web spider Nephila inaurata madagascariensis (Araneae: Tetragnathidae). The complete cDNA sequences of six subunits were obtained that corresponded to a-, b-, d-, e-, f- and g-type subunits. No evidence for a c-type subunit was found in this species. The inclusion of the N. inaurata hemocyanins in a multiple alignment of the arthropod hemocyanins and the application of the Bayesian method of phylogenetic inference allow, for the first time, a solid reconstruction of the intramolecular evolution of the chelicerate hemocyanin subunits. The branch leading to subunit a diverged first, followed by the common branch of the dimer-forming b and c subunits, while subunits d and f, as well as subunits e and g form common branches. Assuming a clock-like evolution of the chelicerate hemocyanins, a timescale for the evolution of the Chelicerata was obtained that agrees with the fossil record.

  18. Coordinated Observations of Aeolian Features from the Mars Exploration Rovers (MER) and the Mars Express High Resolution Stereo Camera and Other Orbiters

    NASA Technical Reports Server (NTRS)

    Greeley, R.; Thompson, S. D.; Whelley, P. L.; Squyres, S.; Neukum, G.; Arvidson, R.; Malin, M.; Kuzmin, R.; Christensen, P.; Rafkin, S.

    2004-01-01

    Surface features associated with aeolian (wind) processes at the Mars Exploration Rover (MER) landing sites for Spirit (Gusev crater) and Opportunity (Sinus Meridiani) were observed from the surface and from orbit through coordinated observations by the rovers and the Mars Express orbiter High Resolution Stereo Camera and compared with features seen in other orbiter data and with wind vectors predicted by a numerical mesoscale model of the atmosphere.

  19. Global Health Security: The Lessons from the West African Ebola Virus Disease Epidemic and MERS Outbreak in the Republic of Korea.

    PubMed

    Ghsa Preparation Task Force Team

    2015-12-01

    The Ebola virus disease outbreak in West Africa and the Middle East Respiratory Syndrome outbreak in the Republic of Korea have given huge impacts in different aspects. Health security is no more a new coinage. Global health security became more realistic in its practical application. In the perspective of global health, it will be helpful to peruse lessons learned from the Ebola outbreak in West Africa and MERS outbreak in Korea. PMID:27429901

  20. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

    SciTech Connect

    Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; Shi, Wei; Feng, Yang; Wang, Yanping; Wang, Lingshu; Li, Wei; Jiang, Shibo; Dimitrov, Dimiter S.; Zhou, Tongqing

    2015-09-15

    The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

  1. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

    DOE PAGESBeta

    Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; Shi, Wei; Feng, Yang; Wang, Yanping; Wang, Lingshu; Li, Wei; Jiang, Shibo; Dimitrov, Dimiter S.; et al

    2015-09-15

    The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of bindingmore » at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.« less

  2. [Bioinformatics-based Design of Peptide Vaccine Candidates Targeting Spike Protein of MERS-CoV and Immunity analysis in Mice].

    PubMed

    Lan, Jiaming; Lu, Shuai; Deng, Yao; Wen, Bo; Chen, Hong; Wang, Wen; Tan, Wenjie

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a novel human coronavirus and posed great threat to public health world wide,which calls for the development of effective and safe vaccine urgently. In the study, peptide epitopes tagrgeting spike antigen were predicted based on bioinformatics methods. Nine polypeptides with high scores were synthesized and linked to keyhole limpet hemocyanin (KLH). Female BALB/C mice were immunized with individual polypeptide-KLH, and the total IgG was detected by ELISA as well as the cellular mediated immunity (CMI) was analyzed using ELIs-pot assay. The results showed that an individual peptide of YVDVGPDSVKSACIEVDIQQTFFDKTWPRPIDVSKADGI could induce the highest level of total IgG as well as CMI (high frequency of IFN-γ secretion) against MERS-CoV antigen in mice. Our study identified a promising peptide vaccine candidate against MERS-CoV and provided an experimental support for bioinformatics-based design of peptide vaccine.

  3. Screening sourdough samples for gliadin-degrading activity revealed Lactobacillus casei strains able to individually metabolize the coeliac-disease-related 33-mer peptide.

    PubMed

    Alvarez-Sieiro, Patricia; Redruello, Begoña; Ladero, Victor; Martín, Maria Cruz; Fernández, María; Alvarez, Miguel A

    2016-05-01

    A selective culture medium containing acid-hydrolyzed gliadins as the sole nitrogen source was used in the search for sourdough-indigenous lactic acid bacteria (LAB) with gliadin-metabolizing activity. Twenty gliadin-degrading LAB strains were isolated from 10 sourdoughs made in different ways and from different geographical regions. Fifteen of the 20 isolated strains were identified as Lactobacillus casei, a species usually reported as subdominant in sourdough populations. The other 5 gliadin-degrading strains belonged to the more commonly encountered sourdough species Leuconostoc mesenteroides and Lactobacillus plantarum. All these strains were shown to be safe in terms of their resistance to antimicrobial agents. When individually incubated with the α2-gliadin-derived immunotoxic 33-mer peptide (97.5 ppm), half of the L. casei strains metabolized at least 50% of it within 24 h. One strain metabolized 82% of the 33-mer peptide within 8 h and made it fully disappear within 12 h. These results reveal for the first time the presence in sourdough of proteolytic L. casei strains with the capacity to individually metabolize the coeliac-disease-related 33-mer peptide.

  4. Transposon Tagging of a Male-Sterility, Female-Sterility Gene, St8, Revealed that the Meiotic MER3 DNA Helicase Activity Is Essential for Fertility in Soybean

    PubMed Central

    Baumbach, Jordan; Pudake, Ramesh N.; Johnson, Callie; Kleinhans, Kaylin; Ollhoff, Alexandrea; Palmer, Reid G.; Bhattacharyya, Madan K.; Sandhu, Devinder

    2016-01-01

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion from variegated to purple flower indicates excision of Tgm9, and its insertion at a new locus. Previously, we have identified a male-sterile, female-sterile mutant among the selfed progenies of a revertant plant carrying only purple flowers. Co-segregation between Tgm9 and the sterility phenotype suggested that the mutant was generated by insertion of Tgm9 at the St8 locus. The transposon was localized to exon 10 of Glyma.16G072300 that shows high identity to the MER3 DNA helicase involved in crossing over. Molecular analysis of fertile branches from two independent revertant plants confirmed precise excision of Tgm9 from the st8 allele, which restored fertility. In soybean, the gene is expressed in flower-buds, trifoliate leaves and stem. Phylogenetic analysis placed St8 in a clade with the Arabidopsis and rice MER3 suggesting that St8 is most likely the orthologous MER3 soybean gene. This study established the utility of Tgm9 in gene identification as well as in forward and reverse genetics studies. PMID:26930200

  5. [Bioinformatics-based Design of Peptide Vaccine Candidates Targeting Spike Protein of MERS-CoV and Immunity analysis in Mice].

    PubMed

    Lan, Jiaming; Lu, Shuai; Deng, Yao; Wen, Bo; Chen, Hong; Wang, Wen; Tan, Wenjie

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a novel human coronavirus and posed great threat to public health world wide,which calls for the development of effective and safe vaccine urgently. In the study, peptide epitopes tagrgeting spike antigen were predicted based on bioinformatics methods. Nine polypeptides with high scores were synthesized and linked to keyhole limpet hemocyanin (KLH). Female BALB/C mice were immunized with individual polypeptide-KLH, and the total IgG was detected by ELISA as well as the cellular mediated immunity (CMI) was analyzed using ELIs-pot assay. The results showed that an individual peptide of YVDVGPDSVKSACIEVDIQQTFFDKTWPRPIDVSKADGI could induce the highest level of total IgG as well as CMI (high frequency of IFN-γ secretion) against MERS-CoV antigen in mice. Our study identified a promising peptide vaccine candidate against MERS-CoV and provided an experimental support for bioinformatics-based design of peptide vaccine. PMID:27295887

  6. Transposon Tagging of a Male-Sterility, Female-Sterility Gene, St8, Revealed that the Meiotic MER3 DNA Helicase Activity Is Essential for Fertility in Soybean.

    PubMed

    Baumbach, Jordan; Pudake, Ramesh N; Johnson, Callie; Kleinhans, Kaylin; Ollhoff, Alexandrea; Palmer, Reid G; Bhattacharyya, Madan K; Sandhu, Devinder

    2016-01-01

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion from variegated to purple flower indicates excision of Tgm9, and its insertion at a new locus. Previously, we have identified a male-sterile, female-sterile mutant among the selfed progenies of a revertant plant carrying only purple flowers. Co-segregation between Tgm9 and the sterility phenotype suggested that the mutant was generated by insertion of Tgm9 at the St8 locus. The transposon was localized to exon 10 of Glyma.16G072300 that shows high identity to the MER3 DNA helicase involved in crossing over. Molecular analysis of fertile branches from two independent revertant plants confirmed precise excision of Tgm9 from the st8 allele, which restored fertility. In soybean, the gene is expressed in flower-buds, trifoliate leaves and stem. Phylogenetic analysis placed St8 in a clade with the Arabidopsis and rice MER3 suggesting that St8 is most likely the orthologous MER3 soybean gene. This study established the utility of Tgm9 in gene identification as well as in forward and reverse genetics studies. PMID:26930200

  7. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

    PubMed Central

    Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; Shi, Wei; Feng, Yang; Wang, Yanping; Wang, Lingshu; Li, Wei; Jiang, Shibo; Dimitrov, Dimiter S.; Zhou, Tongqing

    2015-01-01

    The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo. PMID:26370782

  8. Screening sourdough samples for gliadin-degrading activity revealed Lactobacillus casei strains able to individually metabolize the coeliac-disease-related 33-mer peptide.

    PubMed

    Alvarez-Sieiro, Patricia; Redruello, Begoña; Ladero, Victor; Martín, Maria Cruz; Fernández, María; Alvarez, Miguel A

    2016-05-01

    A selective culture medium containing acid-hydrolyzed gliadins as the sole nitrogen source was used in the search for sourdough-indigenous lactic acid bacteria (LAB) with gliadin-metabolizing activity. Twenty gliadin-degrading LAB strains were isolated from 10 sourdoughs made in different ways and from different geographical regions. Fifteen of the 20 isolated strains were identified as Lactobacillus casei, a species usually reported as subdominant in sourdough populations. The other 5 gliadin-degrading strains belonged to the more commonly encountered sourdough species Leuconostoc mesenteroides and Lactobacillus plantarum. All these strains were shown to be safe in terms of their resistance to antimicrobial agents. When individually incubated with the α2-gliadin-derived immunotoxic 33-mer peptide (97.5 ppm), half of the L. casei strains metabolized at least 50% of it within 24 h. One strain metabolized 82% of the 33-mer peptide within 8 h and made it fully disappear within 12 h. These results reveal for the first time the presence in sourdough of proteolytic L. casei strains with the capacity to individually metabolize the coeliac-disease-related 33-mer peptide. PMID:27021684

  9. PEDF and PEDF-derived peptide 44mer inhibit oxygen-glucose deprivation-induced oxidative stress through upregulating PPARγ via PEDF-R in H9c2 cells.

    PubMed

    Zhuang, Wei; Zhang, Hao; Pan, Jiajun; Li, Zhimin; Wei, Tengteng; Cui, Huazhu; Liu, Zhiwei; Guan, Qiuhua; Dong, Hongyan; Zhang, Zhongming

    2016-04-01

    Pigment epithelial-derived factor (PEDF) is a glycoprotein with broad biological activities including inhibiting oxygen-glucose deprivation(OGD)-induced cardiomyocytes apoptosis through its anti-oxidative properties. PEDF derived peptide-44mer shows similar cytoprotective effect to PEDF. However, the molecular mechanisms mediating cardiomyocytes apoptosis have not been fully established. Here we found that PEDF and 44mer decreased the content of ROS. This content was abolished by either PEDF-R small interfering RNA (siRNA) or PPARγ antagonist. The level of Lysophosphatidic acid (LPA) and phospholipase A2 (PLA2) was observed as drawn from the ELISA assays. PEDF and 44mer sequentially induced PPARγ expression was observed both in qPCR and Western blot assays. The level of LPA and PLA2 and PPARγ expression increased by PEDF and 44mer was significantly attenuated by PEDF-R siRNA. However, PEDF and 44mer inhibited the H9c2 cells and cultured neonatal rat myocardial cells apoptosis rate. On the other hand, TUNEL assay and cleavage of procaspase-3 showed that PEDF-R siRNA or PPARγ antagonist increased the apoptosis again. We conclude that under OGD condition, PEDF and 44mer reduce H9c2 cells apoptosis and inhibit OGD-induced oxidative stress via its receptor PEDF-R and the PPARγ signaling pathway. PMID:26966066

  10. Estimation of MERS-Coronavirus Reproductive Number and Case Fatality Rate for the Spring 2014 Saudi Arabia Outbreak: Insights from Publicly Available Data

    PubMed Central

    Majumder, Maimuna S.; Rivers, Caitlin; Lofgren, Eric; Fisman, David

    2014-01-01

    Background: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was initially recognized as a source of severe respiratory illness and renal failure in 2012. Prior to 2014, MERS-CoV was mostly associated with sporadic cases of human illness, of presumed zoonotic origin, though chains of person-to-person transmission in the healthcare setting were reported. In spring 2014, large healthcare-associated outbreaks of MERS-CoV infection occurred in Jeddah and Riyadh, Kingdom of Saudi Arabia. To date the epidemiological information published by public health investigators in affected jurisdictions has been relatively limited. However, it is important that the global public health community have access to information on the basic epidemiological features of the outbreak to date, including the basic reproduction number (R0) and best estimates of case-fatality rates (CFR). We sought to address these gaps using a publicly available line listing of MERS-CoV cases. Methods: R0 was estimated using the incidence decay with exponential adjustment (“IDEA”) method, while period-specific case fatality rates that incorporated non-attributed death data were estimated using Monte Carlo simulation. Results: 707 cases were available for evaluation. 52% of cases were identified as primary, with the rest being secondary. IDEA model fits suggested a higher R0 in Jeddah (3.5-6.7) than in Riyadh (2.0-2.8); control parameters suggested more rapid reduction in transmission in the former city than the latter. The model accurately projected final size and end date of the Riyadh outbreak based on information available prior to the outbreak peak; for Jeddah, these projections were possible once the outbreak peaked. Overall case-fatality was 40%; depending on the timing of 171 deaths unlinked to case data, outbreak CFR could be higher, lower, or equivalent to pre-outbreak CFR. Conclusions: Notwithstanding imperfect data, inferences about MERS-CoV epidemiology important for public health

  11. Mapping Hydration with the Mars Exploration Rover (MER) Pancam Instruments: Recent Results from Opportunity at Endeavour Crater

    NASA Astrophysics Data System (ADS)

    Rice, Melissa S.; Bell, James F., III; Arvidson, Raymond E.; Farrand, William H.; Johnson, Jeffrey R.; Rice, James W.; Ruff, Steven W.; Squyres, Steven W.; Wang, Alian

    2013-04-01

    Using the Mars Exploration Rover (MER) Panoramic Camera (Pancam) instruments, we have developed a "hydration signature" for mapping H2O- and/or OH-bearing materials at Mars landing sites with multispectral visible to near-infrared (Vis-NIR) images. Pancam's 13 narrowband geology filters cover 11 unique wavelengths in the visible and near infrared (434 to 1009 nm) [1-2]. The hydration signature is based on a negative slope from 934 to 1009 nm [3] that characterizes the spectra of hydrated silica-rich rocks and soils observed by MER Spirit; this feature is likely due to the 2ν1 + ν3 H2O combination band and/or the 3νOH overtone centered near ~1000 nm, whose positions vary slightly depending on bonding to nearest-neighbor atoms [4]. The hydration signature is sensitive to many - but not all - hydrated minerals, including silica, gypsum and water ice. At Gusev Crater, the hydration signature is widespread along Spirit's traverse in the Columbia Hills, which adds to the growing body of evidence that aqueous alteration has played a significant role in the complex geologic history of this site [4]. At Meridiani Planum, the hydration signature is associated with a specific stratigraphic layer ("Smith") exposed within the walls of Victoria Crater [5], in addition to light-toned veins composed of calcium sulfate at Cape York on the rim of Endeavour Crater [6]. Recently, Opportunity has completed a traverse loop at Matijevic Hill at the southern end of Cape York and has encountered numerous small, light-toned, fracture-filling veins that may be indicative of fluid flow. Spectra of these veins are also consistent with hydrated materials, as are spectra of "Whitewater Lake" outcrops at Matijevic Hill, which may contain phyllosilicate minerals [7-8]. Here we also discuss limitations to the use of the hydration signature, which can give false detections under specific viewing geometries. For example, the Pancam calibration model assumes that the calibration target behaves as a

  12. Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital

    PubMed Central

    Kim, Kyung Min; Ki, Moran; Cho, Sung-il; Sung, Minki; Hong, Jin Kwan; Cheong, Hae-Kwan; Kim, Jong-Hun; Lee, Sang-Eun; Lee, Changhwan; Lee, Keon-Joo; Park, Yong-Shik; Kim, Seung Woo; Choi, Bo Youl

    2015-01-01

    OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine. PMID:26725225

  13. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells.

    PubMed

    Wu, Yi-Mi; Robinson, Dan R; Kung, Hsing-Jien

    2004-10-15

    The AXL/UFO family of tyrosine kinases is characterized by a common N-CAM (neural adhesion molecule)-related extracellular domain and a common ligand, GAS6 (growth arrest-specific protein 6). Family members are prone to transcriptional regulation and carry out diverse functions including the regulation of cell adhesion, migration, phagocytosis, and survival. In this report, we describe a new role of MER/N-CAM-related kinase (NYK), a member of the AXL family of kinases, in the up-regulation of chemokines in prostate cancer cells. We show that NYK has elevated expression in a subset of tumor specimens and prostate cancer cell lines. Activation of NYK in the prostate cancer cell line DU145 does not cause a mitogenic effect; instead, it causes a differentiation phenotype. Microarray analysis revealed that NYK is a strong inducer of endocrine factors including interleukin (IL)-8 and several other angiogenic CXC chemokines as well as bone morphogenic factors. The dramatic increase of IL-8 expression is seen at both transcriptional and posttranscriptional levels. The downstream signals engaged by NYK were characterized, and those responsible for the up-regulation of IL-8 transcription were defined. In contrast to IL-1alpha, NYK-induced up-regulation of IL-8 in DU145 depends on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/Jun/Fos pathway, but not phosphoinositide 3'-kinase/nuclear factor-kappaB. These data define a new function of the AXL family of kinases and suggest a potential role of NYK in prostate cancer progression. PMID:15492251

  14. Listeria monocytogenes MerR-Like Regulator NmlRlm: Its Transcriptome and Role in Stress Response.

    PubMed

    Supa-Amornkul, Sirirak; Chantratita, Wasun; Srichunrusami, Chutatip; Janchompoo, Pareena; Chaturongakul, Soraya

    2016-07-01

    NmlR, a negative transcription regulator in the MerR family, is involved in oxidative and nitrosative stress response in Neisseria gonorrhoeae and Haemophilus influenzae. In this study, the objective was to characterize the role and the regulon of NmlR in the foodborne Listeria monocytogenes. An L. monocytogenes nmlR null mutant strain was constructed. Transcriptomes of strain 10403S wild type (WT) and ΔnmlRlm strains grown to the stationary phase were determined by mRNA sequencing. Differential expression analyses revealed 74 genes with altered expression levels (>9-fold difference), comprising 46 negatively and 28 positively regulated genes. Twenty-four NmlRlm-dependent genes overlap with the members of previously identified regulons of HrcA, a negative regulator of heat response in L. monocytogenes, and of alternative sigma factor σ(H). Phenotypic characterization revealed that the ΔnmlRlm strain survived significantly less than the WT under acid stress (pH 2.5 for 1 h) and oxidative stress (3% hydrogen peroxide for 1 h). In addition, nmlRlm deletion also resulted in a significant decrease (p < 0.0005) of cell length and enhanced intracellular growth in a differentiated macrophage-like U937 cell line during entry into stationary phase. These findings indicate that NmlRlm is not only involved in oxidative stress response but also contributes to other characteristics such as acid tolerance and intracellular growth, either through direct regulation or co-regulation with other regulators such as HrcA and σ(H). PMID:27058117

  15. The heavy metal tolerant soil bacterium Achromobacter sp. AO22 contains a unique copper homeostasis locus and two mer operons.

    PubMed

    Ng, Shee Ping; Palombo, Enzo A; Bhave, Mrinal

    2012-06-01

    Copper-containing compounds are introduced into the environment through agricultural chemicals, mining, and metal industries and cause severe detrimental effects on ecosystems. Certain microorganisms exposed to these stressors exhibit molecular mechanisms to maintain intracellular copper homeostasis and avoid toxicity. We have previously reported that the soil bacterial isolate Achromobacter sp. AO22 is multi-heavy metal tolerant and exhibits a mer operon associated with a Tn21 type transposon. The present study reports that AO22 also hosts a unique cop locus encoding copper homeostasis determinants. The putative cop genes were amplified from the strain AO22 using degenerate primers based on reported cop and pco sequences, and a constructed 10,552 base pair contig (GenBank Accession No. GU929214). BLAST analyses of the sequence revealed a unique cop locus of 10 complete open reading frames, designated copSRABGOFCDK, with unusual separation of copCD from copAB. The promoter areas exhibit two putative cop boxes, and copRS appear to be transcribed divergently from other genes. The putative protein CopA may be a copper oxidase involved in export to the periplasm, CopB is likely extracytoplasmic, CopC may be periplasmic, CopD is cytoplasmic/ inner membrane, CopF is a P-type ATPase, and CopG, CopO, and CopK are likely copper chaperones. CopA, B, C, and D exhibit several potential copper ligands and CopS and CopR exhibit features of two-component regulatory systems. Sequences flanking indicate the AO22 cop locus may be present within a genomic island. Achromobacter sp. strain AO22 is thus an ideal candidate for understanding copper homeostasis mechanisms and exploiting them for copper biosensor or biosorption systems. PMID:22573150

  16. Crystallization and preliminary X-ray diffraction data of an LNA 7-mer duplex derived from a ricin aptamer

    PubMed Central

    Förster, Charlotte; Oberthuer, Dominik; Gao, Jiang; Eichert, André; Quast, Frederick G.; Betzel, Christian; Nitsche, Andreas; Erdmann, Volker A.; Fürste, Jens P.

    2009-01-01

    Locked nucleic acids (LNAs) are modified nucleic acids which contain a modified sugar such as β-d-2′-O,4′-C methylene-bridged ribofuranose or other sugar derivatives in LNA analogues. The β-d-2′-O,4′-C methylene ribofuranose LNAs in particular possess high stability and melting temperatures, which makes them of interest for stabilizing the structure of different nucleic acids. Aptamers, which are DNAs or RNAs targeted against specific ligands, are candidates for substitution with LNAs in order to increase their stability. A 7-­mer helix derived from the terminal part of an aptamer that was targeted against ricin was chosen. The ricin aptamer originally consisted of natural RNA building blocks and showed high affinity in ricin binding. For future stabilization of the aptamer, the terminal helix has been constructed as an ‘all-locked’ LNA and was successfully crystallized in order to investigate its structural properties. Optimization of crystal growth succeeded by the use of different metal salts as additives, such as CuCl2, MgCl2, MnCl2, CaCl2, CoCl2 and ZnSO4. Preliminary X-ray diffraction data were collected and processed to 2.8 Å resolution. The LNA crystallized in space group P65, with unit-cell parameters a = 50.11, b = 50.11, c = 40.72 Å. The crystals contained one LNA helix per asymmetric unit with a Matthews coefficient of 3.17 Å3 Da−1, which implies a solvent content of 70.15%. PMID:19724123

  17. Plasmid replication initiator interactions with origin 13-mers and polymerase subunits contribute to strand-specific replisome assembly

    PubMed Central

    Wawrzycka, Aleksandra; Gross, Marta; Wasaznik, Anna; Konieczny, Igor

    2015-01-01

    Although the molecular basis for replisome activity has been extensively investigated, it is not clear what the exact mechanism for de novo assembly of the replication complex at the replication origin is, or how the directionality of replication is determined. Here, using the plasmid RK2 replicon, we analyze the protein interactions required for Escherichia coli polymerase III (Pol III) holoenzyme association at the replication origin. Our investigations revealed that in E. coli, replisome formation at the plasmid origin involves interactions of the RK2 plasmid replication initiation protein (TrfA) with both the polymerase β- and α-subunits. In the presence of other replication proteins, including DnaA, helicase, primase and the clamp loader, TrfA interaction with the β-clamp contributes to the formation of the β-clamp nucleoprotein complex on origin DNA. By reconstituting in vitro the replication reaction on ssDNA templates, we demonstrate that TrfA interaction with the β-clamp and sequence-specific TrfA interaction with one strand of the plasmid origin DNA unwinding element (DUE) contribute to strand-specific replisome assembly. Wild-type TrfA, but not the TrfA QLSLF mutant (which does not interact with the β-clamp), in the presence of primase, helicase, Pol III core, clamp loader, and β-clamp initiates DNA synthesis on ssDNA template containing 13-mers of the bottom strand, but not the top strand, of DUE. Results presented in this work uncovered requirements for anchoring polymerase at the plasmid replication origin and bring insights of how the directionality of DNA replication is determined. PMID:26195759

  18. Identification of calmodulin isoform-specific binding peptides from a phage-displayed random 22-mer peptide library.

    PubMed

    Choi, Ji Young; Lee, Sang Hyoung; Park, Chan Young; Heo, Won Do; Kim, Jong Cheol; Kim, Min Chul; Chung, Woo Sik; Moon, Byeong Cheol; Cheong, Yong Hwa; Kim, Cha Young; Yoo, Jae Hyuk; Koo, Ja Choon; Ok, Hyun Mi; Chi, Seung-Wook; Ryu, Seong-Eon; Lee, Sang Yeol; Lim, Chae Oh; Cho, Moo Je

    2002-06-14

    Plants express numerous calmodulin (CaM) isoforms that exhibit differential activation or inhibition of CaM-dependent enzymes in vitro; however, their specificities toward target enzyme/protein binding are uncertain. A random peptide library displaying a 22-mer peptide on a bacteriophage surface was constructed to screen peptides that specifically bind to plant CaM isoforms (soybean calmodulin (ScaM)-1 and SCaM-4 were used in this study) in a Ca2+-dependent manner. The deduced amino acid sequence analyses of the respective 80 phage clones that were independently isolated via affinity panning revealed that SCaM isoforms require distinct amino acid sequences for optimal binding. SCaM-1-binding peptides conform to a 1-5-10 ((FILVW)XXX(FILV) XXXX(FILVW)) motif (where X denotes any amino acid), whereas SCaM-4-binding peptide sequences conform to a 1-8-14 ((FILVW)XXXXXX(FAILVW)XXXXX(FILVW)) motif. These motifs are classified based on the positions of conserved hydrophobic residues. To examine their binding properties further, two representative peptides from each of the SCaM isoform-binding sequences were synthesized and analyzed via gel mobility shift assays, Trp fluorescent spectra analyses, and phosphodiesterase competitive inhibition experiments. The results of these studies suggest that SCaM isoforms possess different binding sequences for optimal target interaction, which therefore may provide a molecular basis for CaM isoform-specific function in plants. Furthermore, the isolated peptide sequences may serve not only as useful CaM-binding sequence references but also as potential reagents for studying CaM isoform-specific function in vivo.

  19. Coronaviruses (MERS and SARS)

    MedlinePlus

    ... Patients Procedure for Accessing Lab Services Data Package Requirements AIDS Therapies Resource Guide In Vitro Efficacy Evaluations ... Assurances to Users Application and Approval Process User Requirements Malaria Vaccine Production Services Data Sharing and Release ...

  20. Synthesis, structure, catalytic and calculated non-linear optical properties of cis- and trans-, mer-chlorobis(triphenyl phosphine/triphenyl arsine)-dipicolinato ruthenium III complexes

    NASA Astrophysics Data System (ADS)

    Trivedi, Manoj; Nagarajan, R.; Kumar, Abhinav; Singh, Narendra K.; Rath, Nigam P.

    2011-05-01

    The new mononuclear Ru III complexes cis-, mer-[Ru( k3-dipic)(EPh 3) 2Cl]·2H 2O (E = P ( 1), As ( 2)), (L = 2,6-pyridyldicarboxylate; dipic) have been synthesized and characterized. The X-ray crystal structure of 1 reveals that the coordination geometry around the Ru III center is distorted octahedral in which three sites are occupied by tridentate dipic ligand and remaining three sites are occupied by two mutually cis triphenyl phosphine ligands and one chloride ions. In chloroform solvent, cis-, mer-[Ru( k3-dipic)(EPh 3) 2Cl]·2H 2O (E = P ( 1), As ( 2)) complexes undergoes thermal rearrangement to more stable trans-, mer-[Ru( k3-dipic)(EPh 3) 2Cl] (E = P( 3), As( 4)) complexes. Complexes 1 and 2 show rhombic EPR spectral features, while complex 3 and 4 show tetragonal distortion. The new Ru III complexes 1 and 2 display both Ru III-Ru II reduction and Ru III-Ru IV oxidation processes. These geometric isomers exhibit textbook differences both in spectroscopic as well as structural properties in the solid state. The new complexes 1 and 2 were found to catalyze the oxidation of alcohols to carbonyl derivatives using N-methyl morpholine- N-oxide as co-oxidant. The first static hyperpolarizability ( β) for all of the complexes have been investigated by density functional theory (DFT) which suggests β value increases from trans to cis form. Also, the solvent-induced effects on the non-linear optical properties (NLO) were studied by using self-consistent reaction field (SCRF) method. As the solvent polarity increases, the β value increases monotonically. The electronic absorption bands of 1 have been assigned by time dependent density functional theory (TD-DFT).

  1. PM2, a group 3 LEA protein from soybean, and its 22-mer repeating region confer salt tolerance in Escherichia coli

    SciTech Connect

    Yun Liu; Zheng Yizhi . E-mail: yzzheng@szu.edu.cn

    2005-05-27

    To have knowledge of the effect of soybean PM2 protein in protecting dehydrated cells and its functional region, PM2 cDNA was isolated from soybean immature seeds. The recombinants expressing full-length PM2, truncated polypeptides of PM2A (aa 1-262) or PM2B (aa 129-262, 22-mer repeating region), or artificial polypeptide PM2C (duplication of 22-mer repeating region) were constructed. By using SDS-PAGE and mass spectrometry approaches, these fusion polypeptides were identified and proved to be hydrophilic and heat-stable. Spot assays of BL/PM2 and BL/pET28 (as control) showed that protein PM2 increased salt tolerance (500 mM NaCl or 500 mM KCl) of Escherichia coli, rather than osmotic tolerance (1100 mM sorbitol). In addition, comparing the survival ratios of the transformants under 500 mM NaCl or 500 mM KCl stresses, the results showed that: (1) the survival ratios of BL/PM2 and BL/PM2B were quite similar, both showing much higher values than those of BL/pET28. (2) The survival ratios of BL/PM2C were much higher than those of BL/PM2, BL/PM2A, and BL/PM2B. This provides the first experimental evidence that PM2 polypeptide enhances salt tolerance of E. coli cells, and the 22-mer repeat region is an important functional region.

  2. PM2, a group 3 LEA protein from soybean, and its 22-mer repeating region confer salt tolerance in Escherichia coli.

    PubMed

    Liu, Yun; Zheng, Yizhi

    2005-05-27

    To have knowledge of the effect of soybean PM2 protein in protecting dehydrated cells and its functional region, PM2 cDNA was isolated from soybean immature seeds. The recombinants expressing full-length PM2, truncated polypeptides of PM2A (aa 1-262) or PM2B (aa 129-262, 22-mer repeating region), or artificial polypeptide PM2C (duplication of 22-mer repeating region) were constructed. By using SDS-PAGE and mass spectrometry approaches, these fusion polypeptides were identified and proved to be hydrophilic and heat-stable. Spot assays of BL/PM2 and BL/pET28 (as control) showed that protein PM2 increased salt tolerance (500 mM NaCl or 500 mM KCl) of Escherichia coli, rather than osmotic tolerance (1100 mM sorbitol). In addition, comparing the survival ratios of the transformants under 500 mM NaCl or 500 mM KCl stresses, the results showed that: (1) the survival ratios of BL/PM2 and BL/PM2B were quite similar, both showing much higher values than those of BL/pET28. (2) The survival ratios of BL/PM2C were much higher than those of BL/PM2, BL/PM2A, and BL/PM2B. This provides the first experimental evidence that PM2 polypeptide enhances salt tolerance of E. coli cells, and the 22-mer repeat region is an important functional region.

  3. ÉmerGéantes: a new Global Climate Model to study the dynamics of Saturn's stratosphere - and beyond

    NASA Astrophysics Data System (ADS)

    Spiga, Aymeric; Guerlet, Sandrine; Sylvestre, Melody; Fouchet, Thierry

    2013-04-01

    Recent observational programs, both spatial and ground-based, have revealed the complexity of the middle atmospheres of giant planets. In particular, maps of the temperature and of the distribution of trace species in the Saturn stratosphere have been obtained by the Cassini spacecraft with unprecedented details. These maps exhibit puzzling anomalies, which cannot be explained by current photochemical and radiative models (none of them includes dynamics), and which have been interpreted as the signature of large-scale or seasonal dynamical motions. Yet Saturn's global circulation remains weakly characterized. Furthermore, on Saturn and Jupiter, equatorial oscillations in the zonal wind and temperature field have recently been discovered and are reminiscent of the Earth's Quasi-Biennial Oscillation, a fundamental dynamical phenomenon. These oscillations thus appear to be a common dynamical phenomenon in very different planetary atmospheres. We will present the development of "ÉmerGéantes", a new global climate model for giant planets. This new model is based on the LMDz dynamical core, which has been successfully adapted to terrestrial planets and moons: the Earth, Mars, Venus, Titan, Triton/Pluton. Details on the numerical challenges, the adaptations needed to simulate gas giants, and the optimization of the radiative transfer computations will be presented, along with preliminary results. The aim of this project is study in detail the atmospheric circulation of giant planets by resolving atmospheric circulations in their stratosphere (and, possibly, in the future, the coupling between their troposphere and stratosphere). It will serve as a new tool to address fundamental questions in geophysical fluid dynamics, explore the giant planets circulation patterns, and better interpret current and future observations. This new GCM will first be focused on reproducing Saturn's climate, following the harvest of observations obtained by the Cassini mission. We plan to

  4. Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

    SciTech Connect

    Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E; Tuskan, Gerald A

    2004-01-01

    In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16 kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.

  5. Rates and Controls of N2 Fixation in Sphagnum spp. along the Hydrological Gradient - Beaver Pond to Bog Transition at Mer Bleue, Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Zivkovic, T.; Moore, T. R.

    2014-12-01

    Many northern bogs with low atmospheric N inputs acquire N only via N2-fixation. Little is known about rates and controls on N2-fixation in bogs. The aim of this study was to: 1) test the important ecological drivers for N2-fixation, 2) investigate seasonal and temporal patterns of N2 fixation, and 3) to estimate current N2-fixation rates at Mer Bleue bog. We used acetylene reduction assay (ARA) to measure N2-fixation from June-October 2013 and 2014 (currently ongoing field season) along a hydrological gradient (beaver pond, hollows and hummocks). The highest ARA rates in 2013 growing season occurred in the pond in floating Sphagnum cuspidatum mats (50.3 ± 12.9 μmol m-2 d-1 Mean ± Std Err) which were up to 2.5 times latger than the rates found in the hummock with the lowest water table depth throughout the season. Two rain events during the summer 2013 increased ARA rates in all plots by 1 to 4 times, suggesting that moisture availability may play a crucial role on N2 fixation potential in the field. We are currently investigating the role of moisture, temperature, PAR and nutrient content (N, phosphorous and metals) on ARA along the gradient. In addition, we are using 15N2 enrichment method to estimate N2 fixation rates and compare them to ARA method at Mer Bleue bog.

  6. Identification of Position-Specific Correlations between DNA-Binding Domains and Their Binding Sites. Application to the MerR Family of Transcription Factors

    PubMed Central

    Mironov, Andrey A.; Rakhmaininova, Alexandra B.; Gelfand, Mikhail S.

    2016-01-01

    The large and increasing volume of genomic data analyzed by comparative methods provides information about transcription factors and their binding sites that, in turn, enables statistical analysis of correlations between factors and sites, uncovering mechanisms and evolution of specific protein-DNA recognition. Here we present an online tool, Prot-DNA-Korr, designed to identify and analyze crucial protein-DNA pairs of positions in a family of transcription factors. Correlations are identified by analysis of mutual information between columns of protein and DNA alignments. The algorithm reduces the effects of common phylogenetic history and of abundance of closely related proteins and binding sites. We apply it to five closely related subfamilies of the MerR family of bacterial transcription factors that regulate heavy metal resistance systems. We validate the approach using known 3D structures of MerR-family proteins in complexes with their cognate DNA binding sites and demonstrate that a significant fraction of correlated positions indeed form specific side-chain-to-base contacts. The joint distribution of amino acids and nucleotides hence may be used to predict changes of specificity for point mutations in transcription factors. PMID:27690309

  7. Public health response to two incidents of confirmed MERS-CoV cases travelling on flights through London Heathrow Airport in 2014 – lessons learnt.

    PubMed

    Parry-Ford, F; Boddington, N; Pebody, R; Phin, N

    2015-01-01

    In May 2014, Public Health England was alerted to two separate laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection who transited through London Heathrow Airport while symptomatic on flights from Saudi Arabia to the United States of America. We present the rationale for the public health response to both incidents, and report results of contact tracing. Following a risk assessment, passengers seated two seats around the cases were prioritised for contact tracing and a proactive media approach was used to alert all passengers on the planes of their possible exposure in both incidents. In total, 64 United Kingdom (UK) residents were successfully contacted, 14 of whom were sat in the priority area two seats all around the case(s). Five passengers reported respiratory symptoms within 14 days of the flight, but all tested were negative for MERS-CoV. Details of non-UK residents were passed on to relevant World Health Organization International Health Regulation focal points for follow-up, and no further cases were reported back. Different approaches were used to manage contact tracing for each flight due to variations in the quality and timeliness of the passenger contact information provided by the airlines involved. No evidence of symptomatic onward transmission was found. PMID:25990234

  8. Estimation of the genome sizes of the chigger mites Leptotrombidium pallidum and Leptotrombidium scutellare based on quantitative PCR and k-mer analysis

    PubMed Central

    2014-01-01

    Background Leptotrombidium pallidum and Leptotrombidium scutellare are the major vector mites for Orientia tsutsugamushi, the causative agent of scrub typhus. Before these organisms can be subjected to whole-genome sequencing, it is necessary to estimate their genome sizes to obtain basic information for establishing the strategies that should be used for genome sequencing and assembly. Method The genome sizes of L. pallidum and L. scutellare were estimated by a method based on quantitative real-time PCR. In addition, a k-mer analysis of the whole-genome sequences obtained through Illumina sequencing was conducted to verify the mutual compatibility and reliability of the results. Results The genome sizes estimated using qPCR were 191 ± 7 Mb for L. pallidum and 262 ± 13 Mb for L. scutellare. The k-mer analysis-based genome lengths were estimated to be 175 Mb for L. pallidum and 286 Mb for L. scutellare. The estimates from these two independent methods were mutually complementary and within a similar range to those of other Acariform mites. Conclusions The estimation method based on qPCR appears to be a useful alternative when the standard methods, such as flow cytometry, are impractical. The relatively small estimated genome sizes should facilitate whole-genome analysis, which could contribute to our understanding of Arachnida genome evolution and provide key information for scrub typhus prevention and mite vector competence. PMID:24947244

  9. Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014

    PubMed Central

    2014-01-01

    Background In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. Methods All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. Results Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. Conclusions This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian

  10. k-merSNP discovery: Software for alignment-and reference-free scalable SNP discovery, phylogenetics, and annotation for hundreds of microbial genomes

    SciTech Connect

    2014-11-18

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs or raw, unassembled reads. The method is fast to compute, finding SNPs and building a SNP phylogeny in minutes to hours, depending on the size and diversity of the input sequences. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle many gigabases of sequence in a single run. The algorithm is based on k-mer analysis.

  11. Two new hemoglobin variants: Hb Brem-sur-Mer [beta9(A6)Ser-->Tyr] and Hb Passy [alpha81(F2)Ser-->Pro (alpha2)].

    PubMed

    Lacan, Philippe; Moreau, Mathieu; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Louis, Jean-Jacques; Couprie, Nicole; Francina, Alain

    2005-01-01

    Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TCT-->TAT); beta9(A6)Ser-->Tyr] on the first exon of the beta-globin gene and Hb Passy [codon 81 (TCC-->CCC); alpha81(F2)Ser-->Pro (alpha2)] on the second exon of the alpha2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an alpha-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible alpha-thalassemia (thal).

  12. The daily computed weighted averaging basic reproduction number R>0,k,ωn for MERS-CoV in South Korea

    NASA Astrophysics Data System (ADS)

    Jeong, Darae; Lee, Chang Hyeong; Choi, Yongho; Kim, Junseok

    2016-06-01

    In this paper, we propose the daily computed weighted averaging basic reproduction number R0,k,ωn for Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, May to July 2015. We use an SIR model with piecewise constant parameters β (contact rate) and γ (removed rate). We use the explicit Euler's method for the solution of the SIR model and a nonlinear least-square fitting procedure for finding the best parameters. In R0,k,ωn, the parameters n, k, and w denote days from a reference date, the number of days in averaging, and a weighting factor, respectively. We perform a series of numerical experiments and compare the results with the real-world data. In particular, using the predicted reproduction number based on the previous two consecutive reproduction numbers, we can predict the future behavior of the reproduction number.

  13. k-merSNP discovery: Software for alignment-and reference-free scalable SNP discovery, phylogenetics, and annotation for hundreds of microbial genomes

    2014-11-18

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs or raw, unassembled reads. The method is fast to compute, finding SNPs and building a SNP phylogeny inmore » minutes to hours, depending on the size and diversity of the input sequences. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle many gigabases of sequence in a single run. The algorithm is based on k-mer analysis.« less

  14. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces123

    PubMed Central

    Comino, Isabel; Real, Ana; Vivas, Santiago; Síglez, Miguel Ángel; Caminero, Alberto; Nistal, Esther; Casqueiro, Javier; Rodríguez-Herrera, Alfonso; Cebolla, Ángel

    2012-01-01

    Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available. Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces. Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody. Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients. Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867. PMID:22258271

  15. Synthesis, crystal structures and magnetic properties of mer-cyanideiron(III)-based 1D heterobimetallic cyanide-bridged chiral coordination polymers.

    PubMed

    Zhang, Daopeng; Zhuo, Shuping; Zhang, Hongyan; Wang, Ping; Jiang, Jianzhuang

    2015-03-14

    Two pairs of cyanide-bridged Fe(III)–Mn(III)/Cu(II) chiral enantiomer coordination polymers {[Mn(S,S/R,R-Salcy)(CH3OH)2]{[Mn(S,S/R,R-Salcy)][Fe(bbp)(CN)3]}}2n (1,2) (bbp = bis(2-benzimidazolyl)pyridine dianion) and {[Cu(S,S/R,R-Chxn)2]2[Fe2(tbbp)(CN)6]}n (3,4) (tbbp = tetra(3-benzimidazolyl)-4,4′-bipyridine tetraanion) have been successfully prepared by employing mer-tricyanometallate [PPh4]2[Fe(bbp)(CN)3] or the newly bimetallic mer-cyanideiron(III) precursor K4[Fe2(tbbp)(CN)6] as building blocks and with chiral manganese(III)/copper(II) compounds as assemble segments. The four complexes have been characterized by elemental analysis, IR spectroscopy, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra. Single X-ray diffraction reveals that complexes 1 and 2 possess a single anionic chain structure consisting of the asymmetric chiral {[Mn(S,S/R,R-Salcy)][Fe(bbp)(CN)3]}2(2−) unit with free [Mn(S,S/R,R-Salcy)](+) as balanced cations. The cyanide-bridged Fe(III)–Cu(II) complexes 3 and 4 can be structurally characterized as neutral ladder-like double chains composed of the alternating cyanide-bridged Fe–Cu units. Our investigation of magnetic susceptibilities reveals the antiferromagnetic coupling between the cyanide-bridged Fe(III) and Mn(III)/Cu(II) ions for complexes 1–4. These results have been further confirmed by theoretical simulation through numerical matrix diagonalization techniques using a Fortran program or a uniform chain model, leading to the coupling constants J = −7.36 cm(−1), D = −1.52 cm(−1) (1) and J = −4.35 cm(−1) (3), respectively. PMID:25661782

  16. Chromosomal Locus for Cadmium Resistance in Pseudomonas putida Consisting of a Cadmium-Transporting ATPase and a MerR Family Response Regulator

    PubMed Central

    Lee, Seon-Woo; Glickmann, Eric; Cooksey, Donald A.

    2001-01-01

    Pseudomonads from environmental sources vary widely in their sensitivity to cadmium, but the basis for this resistance is largely uncharactarized. A chromosomal fragment encoding cadmium resistance was cloned from Pseudomonas putida 06909, a rhizosphere bacterium, and sequence analysis revealed two divergently transcribed genes, cadA and cadR. CadA was similar to cadmium-transporting ATPases known mostly from gram-positive bacteria, and to ZntA, a lead-, zinc-, and cadmium-transporting ATPase from Escherichia coli. CadR was related to the MerR family of response regulators that normally control mercury detoxification in other bacterial systems. A related gene, zntR, regulates zntA in E. coli, but it is not contiguous with zntA in the E. coli genome as cadA and cadR were in P. putida. In addition, unlike ZntA and other CadA homologs, but similar to the predicted product of gene PA3690 in the P. aeruginosa genome, the P. putida CadA sequence had a histidine-rich N-terminal extension. CadR and the product of PA3689 of P. aeruginosa also had histidine-rich C-terminal extensions not found in other MerR family response regulators. Mutational analysis indicated that cadA and cadR are fully responsible for cadmium resistance and partially for zinc resistance. However, unlike zntA, they did not confer significant levels of lead resistance. The cadA promoter was responsive to Cd(II), Pb(II), and Zn(II), while the cadR promoter was only induced by Cd(II). CadR apparently represses its own expression at the transcriptional level. However, CadR apparently does not repress cadA. Homologs of the cadmium-transporting ATPase were detected in many other Pseudomonas species. PMID:11282588

  17. Benthic trophic network in the Bay of Banyuls-sur-Mer (northwest Mediterranean, France): An assessment based on stable carbon and nitrogen isotopes analysis

    NASA Astrophysics Data System (ADS)

    Carlier, Antoine; Riera, Pascal; Amouroux, Jean-Michel; Bodiou, Jean-Yves; Grémare, Antoine

    2007-03-01

    The benthic trophic network in the Bay of Banyuls-sur-Mer was studied through the carbon and nitrogen isotopic characterization of a large set of soft-bottom macrobenthic invertebrates, fishes and potential food sources. Continental inputs as well as seagrass meadows did not contribute significantly to this benthic trophic network as indicated by: (1) the difference between their δ 13C signatures (respectively -28.4‰ and -9.5‰) and those of sampled animals (between -21.0‰ and -14.6‰); and (2) their low inputs to the bay. Benthic primary consumers fed mostly on surface sediment organic matter (SSOM), which tightly interacts with suspended particulate organic matter (SPOM) and sedimenting organic matter (STOM) due to sediment resuspension. Our results also suggest the occurrence of a transfer between marine SPOM and some invertebrates (e.g. Veretillum cynomorium) and fishes (e.g. Boops boops and Spicara melanurus) through zooplankton. Moreover, the different types of primary consumers (i.e., suspension-feeders, interface-feeders, surface deposit-feeders and subsurface deposit-feeders) preferentially used distinct fractions of the heterogeneous SPOM-STOM-SSOM pool. These differences were mostly related with feeding depth and resulted in distinct isotopic signatures. Differences in the stable isotopic ratios of suspension and interface-feeders could also partly reflect the use of microphytobenthos by the later. Assuming a 15N-enrichment factor of 3.4‰ between the lower and upper ranges of two successive trophic levels, we estimated that the benthic food web of the Bay of Banyuls-sur-Mer was composed of 4 trophic levels. The comparison with our δ 13C values suggests that the whole trophic food chain is affected by continental inputs at the immediate vicinity of the Rhône River mouth even though these effects are maximal for deposit-feeding and carnivorous polychaetes.

  18. Crystal structures of two forms of a 14-mer RNA/DNA chimer duplex with double UU bulges: a novel intramolecular U*(A x U) base triple.

    PubMed

    Deng, J; Xiong, Y; Sudarsanakumar, C; Shi, K; Sundaralingam, M

    2001-10-01

    The RNA/DNA 14-mer, (gguauuucgguaCc)2 with consecutive uridine bulges (underlined) on each strand has been determined in two crystal forms, spermine bound (Sp-form) and spermine free (Sp-free). The former was solved by the MAD method with three-wavelength data collected at Brookhaven National Laboratory (BNL); the later isomorphous structure was solved by the molecular replacement method using data collected on our Raxis IIc imaging plate system. The two crystal forms belong to the space group C2 with one molecule of double-stranded 14 mer in the asymmetric unit. The Sp-form has cell constants, a = 60.06, b = 29.10, c = 52.57 A, beta = 120.79 degrees and was refined to 1.7 A resolution with a final Rwork/Rfree of 19.8%/22.7% using 8,549 independent reflections. The Sp-free structure has cell constants, a = 60.06, b = 29.58, c = 52.50 A, beta = 120.85 degrees and was refined to 1.8 A with a final Rwork/ Rfree of 20.8%/23.2% using 6,285 unique reflections. The two structures are identical, except that the Sp-form has a spermine bound in the major groove, parallel to the RNA helical axis. One of the uridine bulges forms a novel intramolecular U*(A x U) base triple. The helices are in the C3'-endo conformation (A-form), but the bulges adopt the C2'-endo sugar pucker. Furthermore, the bulges induce a kink (30 degrees) in the helix axis and a very large twist (55 degrees) between the base pairs flanking the bulges. The Sp-form has one Mg2+ ion whereas the Sp-free form has two Mg2+ ions.

  19. Crystal Structure of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune Suppression*

    PubMed Central

    Bailey-Elkin, Ben A.; Knaap, Robert C. M.; Johnson, Garrett G.; Dalebout, Tim J.; Ninaber, Dennis K.; van Kasteren, Puck B.; Bredenbeek, Peter J.; Snijder, Eric J.; Kikkert, Marjolein; Mark, Brian L.

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging human pathogen that was first isolated in 2012. MERS-CoV replication depends in part on a virus-encoded papain-like protease (PLpro) that cleaves the viral replicase polyproteins at three sites releasing non-structural protein 1 (nsp1), nsp2, and nsp3. In addition to this replicative function, MERS-CoV PLpro was recently shown to be a deubiquitinating enzyme (DUB) and to possess deISGylating activity, as previously reported for other coronaviral PLpro domains, including that of severe acute respiratory syndrome coronavirus. These activities have been suggested to suppress host antiviral responses during infection. To understand the molecular basis for ubiquitin (Ub) recognition and deconjugation by MERS-CoV PLpro, we determined its crystal structure in complex with Ub. Guided by this structure, mutations were introduced into PLpro to specifically disrupt Ub binding without affecting viral polyprotein cleavage, as determined using an in trans nsp3↓4 cleavage assay. Having developed a strategy to selectively disable PLpro DUB activity, we were able to specifically examine the effects of this activity on the innate immune response. Whereas the wild-type PLpro domain was found to suppress IFN-β promoter activation, PLpro variants specifically lacking DUB activity were no longer able to do so. These findings directly implicate the DUB function of PLpro, and not its proteolytic activity per se, in the inhibition of IFN-β promoter activity. The ability to decouple the DUB activity of PLpro from its role in viral polyprotein processing now provides an approach to further dissect the role(s) of PLpro as a viral DUB during MERS-CoV infection. PMID:25320088

  20. Syntheses, X-ray structures, photochemistry, redox properties, and DFT calculations of interconvertible fac- and mer-[Mn(SPS)(CO)3] isomers containing a flexible SPS-based pincer ligand.

    PubMed

    Doux, Marjolaine; Mézailles, Nicolas; Ricard, Louis; Le Floch, Pascal; Vaz, Pedro D; Calhorda, Maria José; Mahabiersing, Taasje; Hartl, Frantisek

    2005-12-12

    The lithium salt of the anionic SPS pincer ligand composed of a central hypervalent lambda4-phosphinine ring bearing two ortho-positioned diphenylphosphine sulfide side arms reacts with [Mn(CO)5Br] to give fac-[Mn(SPS)(CO)3]. This isomer can be converted photochemically to mer-[Mn(SPS)(CO)3], with a very high quantum yield (0.80+/-0.05). The thermal backreaction is slow (taking ca. 8 h at room temperature), in contrast to rapid electrode-catalyzed mer-to-fac isomerization triggered by electrochemical reduction of mer-[Mn(SPS)(CO)3]. Both geometric isomers of [Mn(SPS)(CO)3] have been characterized by X-ray crystallography. Both isomers show luminescence from a low-lying 3IL (SPS-based) excited state. The light emission of fac-[Mn(SPS)(CO)3] is largely quenched by the efficient photoisomerization occurring probably from a low-lying Mn-CO dissociative excited state. Density functional theory (DFT) and time-dependent DFT calculations describe the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of fac- and mer-[Mn(CO)3(SPS)] as ligand-centered orbitals, largely localized on the phosphinine ring of the SPS pincer ligand. In line with the ligand nature of its frontier orbitals, fac-[Mn(SPS)(CO)3] is electrochemically reversibly oxidized and reduced to the corresponding radical cation and anion, respectively. The spectroscopic (electron paramagnetic resonance, IR, and UV-vis) characterization of the radical species provides other evidence for the localization of the redox steps on the SPS ligand. The smaller HOMO-LUMO energy difference in the case of mer-[Mn(CO)3(SPS)], reflected in the electronic absorption and emission spectra, corresponds with its lower oxidation potential compared to that of the fac isomer. The thermodynamic instability of mer-[Mn(CO)3(SPS)], confirmed by the DFT calculations, increases upon one-electron reduction and oxidation of the complex.

  1. Comparing Apollo and Mars Exploration Rover (MER)/phoenix operations paradigms for human exploration during NASA Desert-RATS science operations

    NASA Astrophysics Data System (ADS)

    Yingst, R. A.; Cohen, B. A.; Ming, D. W.; Eppler, D. B.

    2013-10-01

    The Desert Research and Technology Studies (D-RATS) field tested two models of human-in-the-loop remote field geology: one based on the Apollo science backroom that integrated tactical and strategic decisions, and one that separated tactical and strategic processes as utilized during the Mars Exploration Rovers (MER) and Mars Phoenix Scout missions. The 2010 D-RATS field test was the first attempt at integrating best practices from these two models, to determine how best to maximize science return from future missions. The Apollo model was utilized in 2008 and 2009 as a way to integrate science into field analog studies; the model allowed for real time communications between the crew on the surface and the scientists in the backroom. This model greatly improved efficiency of field operations and scientific return, but did not allow sufficient time for hypotheses to mature to the point where they could inform operations. The MER/Phoenix model, adapted for the 2010 D-RATS test, divided the responsibilities and processes of tactical science and strategic science. This division provided opportunities to discuss science results in greater detail so that the overall planning of science observations could be iterative rather than static. However, because of the nearly complete separation of the two science teams, there was a great deal of repeated effort as the strategic team had no prior knowledge of the tactical process and the observations that led to certain tactical decisions. Lessons learned from 2010 D-RATS science operations include: (1) well-trained geologists on the crew and a science backroom with which that crew can interact are both critical components for maximizing science return; (2) sufficient time or another mechanism that increases time available to be spent on science analysis must be built into the system to allow free rein to the scientific process; (3) data flow must be improved so that time is not wasted in repetitive review of acquired datasets

  2. Synthesis, structures, and photophysical properties of π-expanded oligothiophene 8-mers and their Saturn-like C₆₀ complexes.

    PubMed

    Shimizu, Hideyuki; Cojal González, José D; Hasegawa, Masashi; Nishinaga, Tohru; Haque, Tahmina; Takase, Masayoshi; Otani, Hiroyuki; Rabe, Jürgen P; Iyoda, Masahiko

    2015-03-25

    Two isomers of a multifunctional π-expanded macrocyclic oligothiophene 8-mer, E,E-1 and Z,Z-1, were synthesized using a McMurry coupling of a dialdehyde composed of four 2,5-thienylene and three ethynylene units under high dilution conditions. On the other hand, cyclo[8](2,5-thienylene-ethynylene) 2 was synthesized by intramolecular Sonogashira cyclization of ethynyl bromide 5. From STM measurements, both E,E-1 and Z,Z-1 formed self-assembled monolayers at the solid-liquid interface to produce porous networks, and from X-ray analyses of E,E-1 and 2, both compounds had a round shape with a honeycomb stacked structure. E,E-1 formed various fibrous polymorphs due to nanophase separation of the macrorings. E,E-1 and Z,Z-1 in solution exhibited photochromism upon irradiation with visible and UV light, respectively, and this photoisomerization was confirmed by using STM. Furthermore, amorphous films of Z,Z-1 and E,E-1 showed photoisomerization, although single crystals, fibers, and square tubes of E,E-1 remained unchanged under similar conditions. E,E-1 with a 12.5-14.7 Å inner cavity incorporated fullerene C60 in the cavity in solution and the solid state to produce a Saturn-like complex, whose structure was determined by X-ray analysis. 2 also formed a Saturn-like complex with C60 in the solid state. These Saturn-like complexes are stabilized by van der Waals interactions between the sulfur atoms of 8-mer and C60. The complexes exhibited charge-transfer interactions in the solid state. Like E,E-1, Saturn-like complex E,E-1⊃C60 formed small cube and fiber structures depending on the solvent used, whereas those of Saturn-like complex 2⊃C60 were limited due to the rigidity of the macroring of 2.

  3. Fusion and Visualization of HiRISE Super-Resolution, Shape-from-Shading DTM with MER Stereo 3D Reconstructions

    NASA Astrophysics Data System (ADS)

    Gupta, S.; Paar, G.; Muller, J. P.; Tao, Y.; Tyler, L.; Traxler, C.; Hesina, G.; Huber, B.; Nauschnegg, B.

    2014-12-01

    The FP7-SPACE project PRoViDE has assembled a major portion of the imaging data gathered so far from rover vehicles, landers and probes on extra-terrestrial planetary surfaces into a unique database, bringing them into a common planetary geospatial context and providing access to a complete set of 3D vision products. One major aim of PRoViDE is the fusion between orbiter and rover image products. To close the gap between HiRISE imaging resolution (down to 25cm for the OrthoRectified image (ORI), down to 1m for the DTM) and surface vision products, images from multiple HiRISE acquisitions are combined into a super resolution data set (Tao & Muller, 2014), increasing to 5cm resolution the Ortho images. Furthermore, shape-from-shading is applied to one of the ORIs at its original resolution for refinement of the HiRISE DTM, leading to DTM ground resolutions of up to 25 cm. After texture-based co-registration with these refined orbiter 3D products, MER PanCam and NavCam 3D image products can be smoothly pasted into a multi-resolution 3D data representation. Typical results from the MER mission are presented by a dedicated real-time rendering tool which is fed by a hierarchical 3D data structure that is able to cope with all involved scales from global planetary scale down to close-up reconstructions in the mm range. This allows us to explore and analyze the geological characteristics of rock outcrops, for example the detailed geometry and internal features of sedimentary rock layers, to aid paleoenvironmental interpretation. This integrated approach enables more efficient development of geological models of martian rock outcrops. The rendering tool also provides measurement tools to obtain geospatial data of surface points and distances between them. We report on novel scientific use cases and the added value potential of the resultant high-quality data set and presentation means to support further geologic investigations. The research leading to these results has

  4. Synthesis, structures, and photophysical properties of π-expanded oligothiophene 8-mers and their Saturn-like C₆₀ complexes.

    PubMed

    Shimizu, Hideyuki; Cojal González, José D; Hasegawa, Masashi; Nishinaga, Tohru; Haque, Tahmina; Takase, Masayoshi; Otani, Hiroyuki; Rabe, Jürgen P; Iyoda, Masahiko

    2015-03-25

    Two isomers of a multifunctional π-expanded macrocyclic oligothiophene 8-mer, E,E-1 and Z,Z-1, were synthesized using a McMurry coupling of a dialdehyde composed of four 2,5-thienylene and three ethynylene units under high dilution conditions. On the other hand, cyclo[8](2,5-thienylene-ethynylene) 2 was synthesized by intramolecular Sonogashira cyclization of ethynyl bromide 5. From STM measurements, both E,E-1 and Z,Z-1 formed self-assembled monolayers at the solid-liquid interface to produce porous networks, and from X-ray analyses of E,E-1 and 2, both compounds had a round shape with a honeycomb stacked structure. E,E-1 formed various fibrous polymorphs due to nanophase separation of the macrorings. E,E-1 and Z,Z-1 in solution exhibited photochromism upon irradiation with visible and UV light, respectively, and this photoisomerization was confirmed by using STM. Furthermore, amorphous films of Z,Z-1 and E,E-1 showed photoisomerization, although single crystals, fibers, and square tubes of E,E-1 remained unchanged under similar conditions. E,E-1 with a 12.5-14.7 Å inner cavity incorporated fullerene C60 in the cavity in solution and the solid state to produce a Saturn-like complex, whose structure was determined by X-ray analysis. 2 also formed a Saturn-like complex with C60 in the solid state. These Saturn-like complexes are stabilized by van der Waals interactions between the sulfur atoms of 8-mer and C60. The complexes exhibited charge-transfer interactions in the solid state. Like E,E-1, Saturn-like complex E,E-1⊃C60 formed small cube and fiber structures depending on the solvent used, whereas those of Saturn-like complex 2⊃C60 were limited due to the rigidity of the macroring of 2. PMID:25699988

  5. Carbonate chemistry and air-sea CO2 flux at a fixed point in a NW Mediterranean Bay, Villefranche-sur-Mer, France

    NASA Astrophysics Data System (ADS)

    De Carlo, E. H.; Mousseau, L.; Passafiume, O.; Drupp, P. S.; Gattuso, J.

    2011-12-01

    The purpose of the Service d'Observation de la Rade de Villefranche-sur-Mer (SO-RADE) is to study the temporal variability of hydrological conditions as well as the abundance and composition of holo- and meroplankton at a fixed station in the bay of Villefranche-sur-Mer, North West Mediterranean. The weekly data collected at this site, designated as "Point B (43° 41.10'N - 7° 18.94'E), since 1957 are recognized as a long-term time series describing the evolution of the hydrological conditions in a coastal environment. Since 2007, historical measurements of hydrological and biological conditions have been complemented by measurements of the CO2-carbonate system parameters. In this contribution we present CO2-carbonate system parameters and ancillary data for the period 2007-2010. The data are evaluated in the context of the physical and biogeochemical processes that contribute to the fluxes of CO2 between the ocean and atmosphere. Seasonal cycles of seawater pCO2 are controlled principally by variations in temperature, showing maxima in the summer and minima during the winters. Normalization of pCO2 to the mean seawater temperature (18oC) results in an apparent reversal of the seasonal cycle with maxima observed in the winters and minima in the summers, consistent with a control of pCO2 by primary productivity. Calculations of "instantaneous fluxes" of CO2 between the ocean and atmosphere show this area to be primarily a weak source of CO2 to the atmosphere during the summer and a weak sink during the winter and near neutral overall (range: -0.3 to +0.3 mmol CO2 m-2 h-1, average: 0.02 mmol CO2 m-2 h-1). We will also provide projections of errors incurred from the estimation of annualized fluxes of CO2 based on weekly measurements relative to daily and high-frequency (3 h) data such as those obtained at the Hawaii Kilo Nalu coastal time series station, which shows similar behavior to the Point B location despite significant differences in climate and hydrological

  6. Distinguishing Na, K, and H3O+ Jarosite and Alunite on Mars using VNIR, Emittance and Mossbauer Spectroscopy on the MER and Mars Express/OMEGA Missions

    NASA Astrophysics Data System (ADS)

    Bishop, J. L.; Rothstein, Y.; Dyar, M. D.; Lane, M. D.; Klima, R. L.; Brophy, G. P.

    2005-12-01

    Jarosite has been identified in layered outcrops in Meridiani by the MER Mossbauer spectrometer [Klingelhofer, et al., 2004] and may be present elsewhere on Mars. We are studying VNIR, emittance and Mossbauer spectroscopy of a suite of synthetic and natural samples of jarosite and alunite from the Brophy collection [e.g. Brophy and Sheridan, 1965]. The characteristic NIR overtones and combination bands in this group differ not only depending on the trivalent cation (e.g. Al for alunite and Fe for jarosite), but also depending on the type of monovalent cation (typically K, Na and/or H3O). The VNIR spectrum of K-jarosite exhibits an OH stretching band at 1.47 um, an OH stretch + 2 bend combination doublet at 1.849 and 1.864 um, plus an OH stretch + bend combination triplet at 2.215, 2.265, and 2.300 um and additional OH and SO4 combination features near 2.40, 2.46, 2.50, 2.60 and 2.62 um. H3O- and Na-jarosite spectra exhibit broader features and the doublet is less resolvable. The spectrum of Na-jarosite contains a band at 1.48 um, a broad asymmetric band near 1.85 um and a triplet near 2.235, 2.275, and 2.310 um, plus additional features near 2.42, 2.47, 2.52, 2.62 and 2.64 um. Band assignments for jarosite and alunite spectra are from Bishop and Murad [2005]. We are in the process of comparing these spectra with the mid-IR and Mossbauer spectra of this jarosite group sample suite in order to perform coordinated analyses for this sulfate group on Mars using the MER and Mars Express datasets. References: Bishop, J. L., and E. Murad (2005), The visible and infrared spectral properties of jarosite and alunite, Am. Miner., 90, 1100-1107. Brophy, G. P., and M. F. Sheridan (1965), Sulfate studies IV: The jarosite-natrojarosite-hydronium jarosite solid solution series, Am. Miner., 50, 1595-1607. Klingelhofer, G., et al. (2004), Jarosite and hematite at Meridiani Planum from Opportunity's Mossbauer spectrometer, Science, 306, 1740-1745.

  7. Calendar-dated glacier variations in the western European Alps during the Neoglacial: the Mer de Glace record, Mont Blanc massif

    NASA Astrophysics Data System (ADS)

    Le Roy, Melaine; Nicolussi, Kurt; Deline, Philip; Astrade, Laurent; Edouard, Jean-Louis; Miramont, Cécile; Arnaud, Fabien

    2015-01-01

    Holocene glacier records from the western European Alps are still sparse, although a number of sites are well suited to constraining pre- and early- Little Ice Age (LIA) glacier advances. The present study provides the first dendrochronologically-based and calendar-dated Neoglacial glacier chronology for the Mont Blanc massif, French Alps. It is based on the analysis of over 240 glacially buried Pinus cembra subfossil logs and wood remains found either embedded-in-till or as detrital material in the Mer de Glace right lateral moraine. Only a few of the samples were found to be 'formally in situ' but we show that some logs were 'virtually in situ' (not rooted but showing little or no evidence of reworking) and could be used to accurately reconstruct past glacier margin behavior in space and time. Uncertainties regarding the other samples may relate to original growth location and/or to outer wood decay. The resulting dates (followed by a '+') were therefore considered maximum-limiting ages for glacier advances. The main burial events - interpreted as glacier advances - occurred between ca 1655+ and 1544+ BC, between ca 1230+ and 1105+ BC, between ca 1013+ and 962+/937+ BC, at ca 802-777 BC, after 608+ BC, between 312 and 337 AD, between ca 485+ AD and 606+ AD, between 1120 and 1178 AD, between ca 1248 and 1278+/1296 AD, and after 1352+ AD. These advances predate the late LIA maxima known from historical sources. The magnitude of the advances gradually increased to culminate in three near-Neoglacial maxima during the 7th, 12th and 13th centuries AD, followed by a first LIA/Neoglacial maximum in the second half of the 14th century AD. The pattern of Neoglacial events described here is coherent with Central and Eastern Alpine glacier chronologies. This indicates marked synchronicity of late Holocene glacier variability and forcing at a regional scale, although occasional differences could be detected between 'Western' and 'Eastern' records. The Mer de Glace record also

  8. Control of copper homeostasis in Escherichia coli by a P-type ATPase, CopA, and a MerR-like transcriptional activator, CopR.

    PubMed

    Petersen, C; Møller, L B

    2000-12-31

    We have isolated and characterized a copper sensitive Escherichia coli mutant that is deficient in the copper transporting P-type ATPase encoded by the copA gene (previously ybaR). Measurements of uptake and efflux of 64Cu by wild-type and mutant cells implicated the CopA protein in copper efflux from the cytoplasm, and further demonstrated that cell-associated copper in intact E. coli cells is distributed between two kinetically distinguishable pools, the ratio of which was dramatically disturbed by the copA mutation. Using a copA-lacZ gene fusion the copA promoter was found to be specifically induced by copper, and this induction was shown to be dependent on a MerR-like transcriptional activator encoded by a previously uncharacterized gene, copR (previously ybbI). In the copA deficient background the copA-lacZ fusion was super induced to very high levels even in the absence of copper addition to the medium, and this induction was dependent on CopR. These results indicated that the cytoplasmic copper concentration was dramatically increased in the copA mutant, in agreement with the 64Cu uptake experiments. Moreover, they implied, that the copper concentration in wild type cells is determined primarily by the CopA efflux pump, while copper is taken up by an essentially constitutive mechanism. PMID:11167016

  9. Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors.

    PubMed

    Sun, Bing; Qi, Nan; Shang, Tao; Wu, Hui; Deng, Tingting; Han, Daishu

    2010-06-01

    Several Toll-like receptors (TLRs) are expressed in Sertoli cells and can trigger testicular innate responses after activation by ligands. TLR signaling pathway must be tightly controlled because unrestrained TLR activation generates a chronic inflammatory milieu that often leads to pathogenesis of the host. However, the regulation of TLR signaling in Sertoli cells remains to be clarified. Here we demonstrate that Tyro3 subfamily of receptor tyrosine kinases, Tyro3, Axl, and Mer (TAM), negatively regulate TLR3 signaling in Sertoli cells. Sertoli cells from TAM triple mutant (TAM(-/-)) mice exhibit an excessive activation of TLR3 in response to its ligand polyinosinic-polycytidylic acid, resulting in the up-regulation of inflammatory cytokines including IL-1beta, IL-6, TNFalpha, and type I interferons (alpha and beta). Growth arrest-specific gene 6 (Gas6), a common ligand of TAM receptors, inhibits the TLR3-driven expression of cytokines in Sertoli cells. This TAM-mediated inhibition of TLR3 signaling in Sertoli cells is transduced through the up-regulation of TLR signaling suppressors suppressor of cytokine signaling-1/3 by Gas6. Moreover, we provide evidence that TAM inhibition of inflammatory cytokine production by Sertoli cells may have physiological significance in vivo. These results illuminate a negative regulatory mechanism of TLR3 signaling in Sertoli cells, which may participate in controlling the testicular innate immune responses to pathogens.

  10. Gliadin fragments and a specific gliadin 33-mer peptide close KATP channels and induce insulin secretion in INS-1E cells and rat islets of langerhans.

    PubMed

    Dall, Morten; Calloe, Kirstine; Haupt-Jorgensen, Martin; Larsen, Jesper; Schmitt, Nicole; Josefsen, Knud; Buschard, Karsten

    2013-01-01

    In non-obese diabetic (NOD) mice, diabetes incidence is reduced by a gluten-free diet. Gluten peptides, such as the compound gliadin, can cross the intestinal barrier and may directly affect pancreatic beta cells. We investigated the effects of enzymatically-digested gliadin in NOD mice, INS-1E cells and rat islets. Six injections of gliadin digest in 6-week-old NOD mice did not affect diabetes development, but increased weight gain (20% increase by day 100). In INS-1E cells, incubation with gliadin digest induced a dose-dependent increase in insulin secretion, up to 2.5-fold after 24 hours. A similar effect was observed in isolated rat islets (1.6-fold increase). In INS-1E cells, diazoxide reduced the stimulatory effect of gliadin digest. Additionally, gliadin digest was shown to decrease current through KATP-channels. A specific gliadin 33-mer had a similar effect, both on current and insulin secretion. Finally, INS-1E incubation with gliadin digest potentiated palmitate-induced insulin secretion by 13% compared to controls. Our data suggest that gliadin fragments may contribute to the beta-cell hyperactivity observed prior to the development of type 1 diabetes. PMID:23785500

  11. Palaeo-ecological quality status based on foraminifera of Boulogne-sur-Mer harbour (Pas-de-Calais, Northeastern France) over the last 200 years.

    PubMed

    Francescangeli, F; Armynot du Chatelet, E; Billon, G; Trentesaux, A; Bouchet, V M P

    2016-06-01

    Over the last centuries, coastal areas have experienced dramatic degradations of their environmental quality, which has led to a huge reduction of marine biodiversity. The objective of the present study was to use geochemical parameters and benthic fossil foraminifera to assess environmental changes that have occurred over the last 200 years in a harbour area (Boulogne-sur-Mer, Northern France) heavily modified by human activities. A multidisciplinary approach including major and trace metals, grain-size, total organic carbon and benthic fossil foraminifera, has been performed on a 33-cm long core. The dating was carried out using the activity of (210)Pb and (137)Cs. Embayment of the area and increase of trace metals concentrations induced a shift in benthic communities. Human activities modified a sandy nearshore bank, colonized by typical marine foraminiferal species, such as Cribroelphiudium excavatum, into a sheltered environment, dominated by brackish end-members, such as Haynesina germanica. Along the sedimentary record, the interaction between meiofaunal and geochemical elements made it possible to distinguish between a pre-impacted period and an industrial period. The upper part of the core reflects better ecological conditions, indicating an environmental recovery. Our results provide baselines for future environmental bio-monitoring in the area. PMID:27074196

  12. Ruthenium complexes as nitric oxide donors and scavengers. Synthesis and crystal and molecular structure for mer,trans-[RuIICl3(NO+)(N-4-ethylisonicotinate)2], and mer,trans-[RuIIICl3(N-CH3CN)(N-4-ethylisonicotinate)2] as obtained via UV-photochemical activation of {RuII(NO+)}3+-core parent complex in acetonitrile solution

    NASA Astrophysics Data System (ADS)

    Tamasi, Gabriella; Cini, Renzo

    2013-09-01

    The synthesis of mer,trans-[RuIICl3(NO+)(EINT)2] (EINT = N-4-ethylisonicotinate), 1, was achieved by carefully working under ultrapure nitrogen atmosphere, by mixing RuIIICl3(NO)·H2O and EINT (1:2 M ratio in anhydrous ethanol) under stirring and at reflux conditions. Single crystals of 1 suitable for X-ray diffraction XRD techniques were also obtained by slow evaporation of solvent under nitrogen from the mother alcoholic solution. The IR spectrum of the solid (KBr matrixes) showed the characteristic sharp and intense band (1866 cm-1) relevant to the N-O stretching vibration for the nitrosyl ligand (RuIINO+ core). Then, on irradiating at 25 °C a solution of 1 in ultrapure acetonitrile (contained in quartz cuvette) under an UV source (250 throughout 366 nm) a color turning from pink to yellow occurred. After a prolonged irradiation (250 nm for at least 6 h) the cuvette (yellow solution) was stored in a dry nitrogen atmosphere and allowed to slowly concentrate via spontaneous solvent evaporation. The solution produced brown crystals as parallelepipeds, suitable for XRD data collection, that belong to the monoclinic system, C2/c space group, and the molecular structure (mer,trans-[RuIICl3(N-NCCH3)(EINT)2], 2) consists of complex molecules that are mostly paired via stacking interactions that involve the pyridine moiety and through (ethyl)CH3⋯Cl(Ru), (pyridine)CH⋯Cl(Ru) and (ethyl)CH3⋯O(C) hydrogen bond type interactions. The crystals of the parent nitrosyl complex belong to the orthorhombic Pccn space group and the complex molecule has three chlorido ligands in the equatorial positions and two EINT ligands in the axial positions. The nitrosyl ligand occupy two positions that are trans to each other and have half occupancy each.

  13. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    PubMed

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection.

  14. Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition.

    PubMed

    Vilenchik, M; Benimetsky, L; Kolbanovsky, A; Miller, P; Stein, C A

    2001-04-01

    We have demonstrated the formation of higher-order structures (presumably tetraplexes) by an 18-mer phosphorothioate antisense c-myb oligodeoxyribonucleotide that has been shown to have activity in the treatment of leukemia xenograft models. Although not observable by conventionally employed techniques, such as PAGE and dimethyl sulfate (DMS) protection, the formation of such higher-order structures by this oligonucleotide was revealed by several techniques. These included capillary gel electrophoresis (CGE), which demonstrated the presence of molecules with greatly increased retention time compared with the monomer; magnetic circular dichroism spectroscopy, which demonstrated a band at 290 nm, a characteristic of antiparallel tetraplexes; and fluorescence energy transfer measurements. For the last, the 18-mer phosphorothioate oligonucleotide was synthesized with a 5'-fluorescein group. Similar to the molecular beacon model, its fluorescence was quenched when combined in solution with tetraplex-forming oligomers that contained a 3'-Dabcyl moiety. 7-Deazaguanosine inhibits the formation of tetraplexes by eliminated Hoogsteen base pair interactions. The wild-type and 7-deazaguanosine-substituted antisense c-myb oligomers differentially downregulated the expression of the c-myb proto-oncogene in K562 and HL60 cells, with the wild-type oligomer being the least active. The 18-mer c-myb molecule can, therefore, form highly complex structures, whose analysis in solution cannot be limited to examination of slab gel electrophoresis results alone.

  15. Photochemistry in a 3D metal-organic framework (MOF): monitoring intermediates and reactivity of the fac-to-mer photoisomerization of Re(diimine)(CO)3Cl incorporated in a MOF.

    PubMed

    Easun, Timothy L; Jia, Junhua; Calladine, James A; Blackmore, Danielle L; Stapleton, Christopher S; Vuong, Khuong Q; Champness, Neil R; George, Michael W

    2014-03-01

    The mechanism and intermediates in the UV-light-initiated ligand rearrangement of fac-Re(diimine)(CO)3Cl to form the mer isomer, when incorporated into a 3D metal-organic framework (MOF), have been investigated. The structure hosting the rhenium diimine complex is a 3D network with the formula {Mn(DMF)2[LRe(CO)3Cl]}∞ (ReMn; DMF = N,N-dimethylformamide), where the diimine ligand L, 2,2'-bipyridine-5,5'-dicarboxylate, acts as a strut of the MOF. The incorporation of ReMn into a KBr disk allows spatial distribution of the mer-isomer photoproduct in the disk to be mapped and spectroscopically characterized by both Fourier transform infrared and Raman microscopy. Photoisomerization has been monitored by IR spectroscopy and proceeds via dissociation of a CO to form more than one dicarbonyl intermediate. The dicarbonyl species are stable in the solid state at 200 K. The photodissociated CO ligand appears to be trapped within the crystal lattice and, upon warming above 200 K, readily recombines with the dicarbonyl intermediates to form both the fac-Re(diimine)(CO)3Cl starting material and the mer-Re(diimine)(CO)3Cl photoproduct. Experiments over a range of temperatures (265-285 K) allow estimates of the activation enthalpy of recombination for each process of ca. 16 (±6) kJ mol(-1) (mer formation) and 23 (±4) kJ mol(-1) (fac formation) within the MOF. We have compared the photochemistry of the ReMn MOF with a related alkane-soluble Re(dnb)(CO)3Cl complex (dnb = 4,4'-dinonyl-2,2'-bipyridine). Time-resolved IR measurements clearly show that, in an alkane solution, the photoinduced dicarbonyl species again recombines with CO to both re-form the fac-isomer starting material and form the mer-isomer photoproduct. Density functional theory calculations of the possible dicarbonyl species aids the assignment of the experimental data in that the ν(CO) IR bands of the CO loss intermediate are, as expected, shifted to lower energy when the metal is bound to DMF rather than to an

  16. Assessment by regional modelling of the impact of monopile foundations on the hydrodynamics and sediment transport: case of Courseulles-sur-Mer (France) wind farm

    NASA Astrophysics Data System (ADS)

    Rivier, Aurélie; Bennis, Anne-Claire; Pinon, Grégory; Magar, Vanesa; Gross, Markus

    2015-04-01

    Offshore monopile foundations of wind turbines modify hydrodynamics and sediment transport at local scale and also at regional scale. The aim of this work is to assess these changes and to parametrize them in a regional model. These modifications were previously evaluated using the regional circulation model MARS3D (Lazure and Dumas, 2008) in tests-cases (Rivier et al., 2014) using two approaches: in the first approach, monopiles are explicitly modelled in the mesh as dry cells and in the second approach a sub-grid parametrization which considers the drag force exerted by a monopile on the flow is used. The sub-grid parametrization is improved close to the bed in this paper by adding a drag force term in the momentum equations, source terms in the turbulence model and by increasing the bed shear stress at monopile location. Changes in hydrodynamics regime, especially near-bed, affect sediment transport regime and modifications due to monopiles on sediment dynamics is also investigated using the MARS3D sediment transport module (Le Hir et al., 2011) which solves the advection-diffusion equations. Test-cases are run using hydrodynamical conditions and sediment grain sizes typical from the area located off Courseulles-sur-Mer (Normandy, France) where an offshore wind farm is planned to be built. Velocity, turbulent kinetic energy and bed thickness changes due to the monopile simulated by both approaches are compared to each other and to experimental measurements made in a flume at the University of Caen or to published data (e.g. Roulund et al., 2005; Dargahi,1989). Then the model is applied in a real configuration on an area including the future offshore wind farm of Courseulles-sur-Mer. Four monopiles are represented in the model using both approaches and modifications of the hydrodynamics and sediment transport are assessed along a tidal cycle. Currents increase at the side edge of the monopile and decrease in front of and downstream the monopile. Turbulent kinetic

  17. The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms.

    PubMed

    Liao, Julie; Schurr, Michael J; Sauer, Karin

    2013-08-01

    A defining characteristic of biofilms is antibiotic tolerance that can be up to 1,000-fold greater than that of planktonic cells. In Pseudomonas aeruginosa, biofilm tolerance to antimicrobial agents requires the biofilm-specific MerR-type transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm tolerance has not been elucidated. Genome-wide transcriptional profiling indicated that brlR was required for maximal expression of genes associated with antibiotic resistance, in particular those encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN. Chromatin immunoprecipitation (ChIP) analysis revealed a direct regulation of these genes by BrlR, with DNA binding assays confirming BrlR binding to the promoter regions of the mexAB-oprM and mexEF-oprN operons. Quantitative reverse transcriptase PCR (qRT-PCR) analysis further indicated BrlR to be an activator of mexAB-oprM and mexEF-oprN gene expression. Moreover, immunoblot analysis confirmed increased MexA abundance in cells overexpressing brlR. Inactivation of both efflux pumps rendered biofilms significantly more susceptible to five different classes of antibiotics by affecting MIC but not the recalcitrance of biofilms to killing by bactericidal agents. Overexpression of either efflux pump in a ΔbrlR strain partly restored tolerance of ΔbrlR biofilms to antibiotics. Expression of brlR in mutant biofilms lacking both efflux pumps partly restored antimicrobial tolerance of biofilms to wild-type levels. Our results indicate that BrlR acts as an activator of multidrug efflux pumps to confer tolerance to P. aeruginosa biofilms and to resist the action of antimicrobial agents.

  18. Human Full-Length Coagulation Factor X and a GLA Domain-Derived 40-mer Polypeptide Bind to Different Regions of the Adenovirus Serotype 5 Hexon Capsomer

    PubMed Central

    Sumarheni, Sudir; Hong, Saw See; Josserand, Véronique; Coll, Jean-Luc; Boulanger, Pierre; Schoehn, Guy

    2014-01-01

    Abstract The interaction of human adenovirus (HAdV)-C5 and many other adenoviruses with blood coagulation factors (e.g., human factor X, FX) involves the binding of their GLA domain to the hexon capsomers, resulting in high levels of hepatotropism and potential hepatotoxicity. In this study, we tested the possibility of preventing these undesirable effects by using a GLA-mimicking peptide as a competitor. An FX GLA domain-derived, 40-mer polypeptide carrying 12 carboxyglutamate residues was synthesized (GLAmim). Surface plasmon resistance (SPR) analysis showed that GLAmim reacted with free and capsid-embedded hexon with a nanomolar affinity. Unexpectedly, GLAmim failed to compete with FX for hexon binding, and instead significantly increased the formation of FX–hexon or FX–adenovirion complexes. This observation was confirmed by in vitro cell transduction experiments using HAdV-C5-Luciferase vector (HAdV5-Luc), as preincubation of HAdV5-Luc with GLAmim before FX addition resulted in a higher transgene expression compared with FX alone. HAdV-C5 virions complexed with GLAmim were analyzed by cryoelectron microscopy. Image reconstruction demonstrated the bona fide hexon–GLAmim interaction, as for the full-length FX, although with considerable differences in stoichiometry and relative location on the hexon capsomer. Three extra densities were found at the periphery of each hexon, whereas one single FX molecule occupied the central cavity of the hexon trimeric capsomer. A refined analysis indicated that each extra density is found at the expected location of one highly variable loop 1 of the hexon, involved in scavenger receptor recognition. HAdV5-Luc complexed with a bifunctional GLAmimRGD peptide showed a lesser hepatotropism, compared with control HAdV5-Luc alone, and efficiently targeted αβ-integrin-overexpressing tumor cells in an in vivo mouse tumor model. Collectively, our findings open new perspectives in the design of adenoviral vectors for biotherapy

  19. Numerical modelling of circulation and dispersion processes in Boulogne-sur-Mer harbour (Eastern English Channel): sensitivity to physical forcing and harbour design

    NASA Astrophysics Data System (ADS)

    Jouanneau, Nicolas; Sentchev, Alexei; Dumas, Franck

    2013-12-01

    The MARS-3D model in conjunction with the particle tracking module Ichthyop is used to study circulation and tracer dynamics under a variety of forcing conditions in the eastern English Channel, and in the Boulogne-sur-Mer harbour (referred to hereafter as BLH). Results of hydrodynamic modelling are validated against the tidal gauge data, VHF radar surface velocities and ADCP measurements. Lagrangian tracking experiments are performed with passive particles to study tracer dispersal along the northern French coast, with special emphasis on the BLH. Simulations revealed an anticyclonic eddy generated in the harbour at rising tide. Tracers, released during flood tide at the Liane river mouth, move northward with powerful clockwise rotating current. After the high water, the current direction changes to westward, and tracers leave the harbour through the open boundary. During ebb tide, currents convergence along the western open boundary but no eddy is formed, surface currents inside the harbour are much weaker and the tracer excursion length is small. After the current reversal at low water, particles are advected shoreward resulting in a significant increase of the residence time of tracers released during ebb tide. The effect of wind on particle dispersion was found to be particularly strong. Under strong SW wind, the residence time of particles released during flood tide increases from 1.5 to 6 days. For release during ebb tide, SW wind weakens the southward tidally induced drift and thus the residence time decreases. Similar effects are observed when the freshwater inflow to the harbour is increased from 2 to 10 m3/s during the ebb tide flow. For flood tide conditions, the effect of freshwater inflow is less significant. We also demonstrate an example of innovative coastal management targeted at the reduction of the residence time of the pathogenic material accidentally released in the harbour.

  20. A folding pathway for betapep-4 peptide 33mer: from unfolded monomers and beta-sheet sandwich dimers to well-structured tetramers.

    PubMed

    Mayo, K H; Ilyina, E

    1998-02-01

    It was recently reported that a de novo designed peptide 33mer, betapep-4, can form well-structured beta-sheet sandwich tetramers (Ilyina E, Roongta V, Mayo KH, 1997b, Biochemistry 36:5245-5250). For insight into the pathway of betapep-4 folding, the present study investigates the concentration dependence of betapep-4 self-association by using 1H-NMR pulsed-field gradient (PFG)-NMR diffusion measurements, and circular dichroism. Downfield chemically shifted alphaH resonances, found to arise only from the well-structured betapep-4 tetramer state, yield the fraction of tetramer within the oligomer equilibrium distribution. PFG-NMR-derived diffusion coefficients, D, provide a means for deriving the contribution of monomer and other oligomer states to this distribution. These data indicate that tetramer is the highest oligomer state formed, and that inclusion of monomer and dimer states in the oligomer distribution is sufficient to explain the concentration dependence of D values for betapep-4. Equilibrium constants calculated from these distributions [2.5 x 10(5) M(-1) for M-D and 1.2 x 10(4) M(-1) for D-T at 313 K] decrease only slightly, if at all, with decreasing temperature indicating a hydrophobically mediated, entropy-driven association/folding process. Conformational analyses using NMR and CD provide a picture where "random coil" monomers associate to form molten globule-like beta-sheet sandwich dimers that further associate and fold as well-structured tetramers. Betapep-4 folding is thermodynamically linked to self-association. As with folding of single-chain polypeptides, the final folding step to well-structured tetramer betapep-4 is rate limiting.

  1. Nutrient Addition Leads to a Weaker CO2 Sink and Higher CH4 Emissions through Vegetation-Microclimate Feedbacks at Mer Bleue Bog, Canada

    NASA Astrophysics Data System (ADS)

    Bubier, J. L.; Arnkil, S.; Humphreys, E.; Juutinen, S.; Larmola, T.; Moore, T. R.

    2015-12-01

    Atmospheric nitrogen (N) deposition has led to nutrient enrichment in wetlands globally, affecting plant community composition, carbon (C) cycling, and microbial dynamics. Nutrient-limited boreal bogs are long-term sinks of carbon dioxide (CO2), but sources of methane (CH4), an important greenhouse gas. We fertilized Mer Bleue Bog, a Sphagnum moss and evergreen shrub-dominated ombrotrophic bog near Ottawa, Ontario, for 10-15 years with N as NO3 and NH4 at 5, 10 and 20 times ambient N deposition (0.6-0.8 g N m-2 y-1), with and without phosphorus (P) and potassium (K). Treatments were applied to triplicate plots (3 x 3 m) from May - August 2000-2015 and control plots received distilled water. We measured net ecosystem CO2 exchange (NEE), ecosystem photosynthesis and respiration, and CH4 flux with climate-controlled chambers; leaf-level CO2 exchange and biochemistry; substrate-induced respiration, CH4 production and consumption potentials with laboratory incubations; plant species composition and abundance; and microclimate (peat temperature, moisture, light interception). After 15 years, we have found that NEE has decreased, and CH4 emissions have increased, in the highest nutrient treatments owing to changes in vegetation, microtopography, and peat characteristics. Vegetation changes include a loss of Sphagnum moss and introduction of new deciduous species. Simulated atmospheric N deposition has not benefitted the photosynthetic apparatus of the dominant evergreen shrubs, but resulted in higher foliar respiration, contributing to a weaker ecosystem CO2 sink. Loss of moss has led to wetter near-surface substrate, higher rates of decomposition and CH4 emission, and a shift in microbial communities. Thus, elevated atmospheric deposition of nutrients may endanger C storage in peatlands through a complex suite of feedbacks and interactions among vegetation, microclimate, and microbial communities.

  2. Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis

    PubMed Central

    Nishiura, Hiroshi; Endo, Akira; Saitoh, Masaya; Kinoshita, Ryo; Ueno, Ryo; Nakaoka, Shinji; Miyamatsu, Yuichiro; Dong, Yueping; Chowell, Gerardo; Mizumoto, Kenji

    2016-01-01

    Objectives To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. Design Retrospective epidemiological analysis. Setting Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. Participants A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. Primary and secondary outcome measures Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. Results A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0–8.6) and 28.6 (0.0–63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. Conclusions Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases. PMID:26908522

  3. Strongly structured DNA sequences as targets for genosensing: sensing phase design and coupling to PCR amplification for a highly specific 33-mer gliadin DNA fragment.

    PubMed

    Martín-Fernández, Begoña; Miranda-Ordieres, Arturo J; Lobo-Castañón, María Jesús; Frutos-Cabanillas, Gloria; de-los-Santos-Álvarez, Noemí; López-Ruiz, Beatriz

    2014-10-15

    Electrochemical genosensors are becoming cost-effective miniaturizable alternatives to real-time PCR (RT-PCR) methods for the detection of sequence-specific DNA fragments. We report on the rapid detection of PCR amplicons without the need of purification or strand separation. A challenging target sequence for both PCR amplification and electrochemical detection allowed us to address some difficulties associated to hybridization on electrode surfaces. The target was a highly specific oligonucleotide sequence of wheat encoding the most immunogenic peptide of gliadin that triggers the immune response of celiac disease (CD), the 33-mer. With a sandwich assay format and a rational design of the capture and tagged-signaling probes the problems posed by the strong secondary structure of the target and complementary probes were alleviated. Using a binary self-assembled monolayer and enzymatic amplification, a limit of detection of 0.3 nM was obtained. The genosensor did not respond to other gluten-containing cereals such as rye and barley. Coupling to PCR to analyze wheat flour samples required tailoring both the capture and signaling probes. This is the first time that deleterious steric hindrance from long single-stranded regions adjacent to the electrode surface is reported for relatively short amplicons (less than 200 bp). The importance of the location of the recognition site within the DNA sequence is discussed. Since the selected gene fragment contains several repetitions of short sequences, a careful optimization of the PCR conditions had to be performed to circumvent the amplification of non-specific fragments from wheat flour.

  4. RhoA/phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein kinase signaling after growth arrest-specific protein 6/mer receptor tyrosine kinase engagement promotes epithelial cell growth and wound repair via upregulation of hepatocyte growth factor in macrophages.

    PubMed

    Lee, Ye-Ji; Park, Hyun-Jung; Woo, So-Youn; Park, Eun-Mi; Kang, Jihee Lee

    2014-09-01

    Growth arrest-specific protein 6 (Gas6)/Mer receptor tyrosine kinase (Mer) signaling modulates cytokine secretion and helps to regulate the immune response and apoptotic cell clearance. Signaling pathways that activate an epithelial growth program in macrophages are still poorly defined. We report that Gas6/Mer/RhoA signaling can induce the production of epithelial growth factor hepatic growth factor (HGF) in macrophages, which ultimately promotes epithelial cell proliferation and wound repair. The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH2-terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. Conditioned medium from RAW 264.7 cells that had been exposed to Gas6 or apoptotic cells enhanced epithelial cell proliferation of the epithelial cell line LA-4 and wound closure. Cotreatment with an HGF receptor-blocking antibody or c-Met antagonist downregulated this enhancement. Inhibition of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and protein expression in macrophages and blocked epithelial cell proliferation and wound closure induced by the conditioned medium. Our data provide evidence that macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway. Thus, defects in Gas6/Mer/RhoA signaling in macrophages may delay tissue repair after injury to the alveolar epithelium.

  5. Statistical properties and time-frequency analysis of temperature, salinity and turbidity measured by the MAREL Carnot station in the coastal waters of Boulogne-sur-Mer (France)

    NASA Astrophysics Data System (ADS)

    Kbaier Ben Ismail, Dhouha; Lazure, Pascal; Puillat, Ingrid

    2016-10-01

    In marine sciences, many fields display high variability over a large range of spatial and temporal scales, from seconds to thousands of years. The longer recorded time series, with an increasing sampling frequency, in this field are often nonlinear, nonstationary, multiscale and noisy. Their analysis faces new challenges and thus requires the implementation of adequate and specific methods. The objective of this paper is to highlight time series analysis methods already applied in econometrics, signal processing, health, etc. to the environmental marine domain, assess advantages and inconvenients and compare classical techniques with more recent ones. Temperature, turbidity and salinity are important quantities for ecosystem studies. The authors here consider the fluctuations of sea level, salinity, turbidity and temperature recorded from the MAREL Carnot system of Boulogne-sur-Mer (France), which is a moored buoy equipped with physico-chemical measuring devices, working in continuous and autonomous conditions. In order to perform adequate statistical and spectral analyses, it is necessary to know the nature of the considered time series. For this purpose, the stationarity of the series and the occurrence of unit-root are addressed with the Augmented-Dickey Fuller tests. As an example, the harmonic analysis is not relevant for temperature, turbidity and salinity due to the nonstationary condition, except for the nearly stationary sea level datasets. In order to consider the dominant frequencies associated to the dynamics, the large number of data provided by the sensors should enable the estimation of Fourier spectral analysis. Different power spectra show a complex variability and reveal an influence of environmental factors such as tides. However, the previous classical spectral analysis, namely the Blackman-Tukey method, requires not only linear and stationary data but also evenly-spaced data. Interpolating the time series introduces numerous artifacts to the

  6. X-ray Structure of a Hg2+ Complex of Mercuric Reductase (MerA) and Quantum Mechanical/Molecular Mechanical Study of Hg2+ Transfer between the C-Terminal and Buried Catalytic Site Cysteine Pairs

    PubMed Central

    2015-01-01

    Mercuric reductase, MerA, is a key enzyme in bacterial mercury resistance. This homodimeric enzyme captures and reduces toxic Hg2+ to Hg0, which is relatively unreactive and can exit the cell passively. Prior to reduction, the Hg2+ is transferred from a pair of cysteines (C558′ and C559′ using Tn501 numbering) at the C-terminus of one monomer to another pair of cysteines (C136 and C141) in the catalytic site of the other monomer. Here, we present the X-ray structure of the C-terminal Hg2+ complex of the C136A/C141A double mutant of the Tn501 MerA catalytic core and explore the molecular mechanism of this Hg transfer with quantum mechanical/molecular mechanical (QM/MM) calculations. The transfer is found to be nearly thermoneutral and to pass through a stable tricoordinated intermediate that is marginally less stable than the two end states. For the overall process, Hg2+ is always paired with at least two thiolates and thus is present at both the C-terminal and catalytic binding sites as a neutral complex. Prior to Hg2+ transfer, C141 is negatively charged. As Hg2+ is transferred into the catalytic site, a proton is transferred from C136 to C559′ while C558′ becomes negatively charged, resulting in the net transfer of a negative charge over a distance of ∼7.5 Å. Thus, the transport of this soft divalent cation is made energetically feasible by pairing a competition between multiple Cys thiols and/or thiolates for Hg2+ with a competition between the Hg2+ and protons for the thiolates. PMID:25343681

  7. Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23

    PubMed Central

    Woo, Patrick C. Y.; Lau, Susanna K. P.; Fan, Rachel Y. Y.; Lau, Candy C. Y.; Wong, Emily Y. M.; Joseph, Sunitha; Tsang, Alan K. L.; Wernery, Renate; Yip, Cyril C. Y.; Tsang, Chi-Ching; Wernery, Ulrich; Yuen, Kwok-Yung

    2016-01-01

    Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1. PMID:27164099

  8. Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.

    PubMed

    Eikawa, Shingo; Kakimi, Kazuhiro; Isobe, Midori; Kuzushima, Kiyotaka; Luescher, Immanuel; Ohue, Yoshihiro; Ikeuchi, Kazuhiro; Uenaka, Akiko; Nishikawa, Hiroyoshi; Udono, Heiichiro; Oka, Mikio; Nakayama, Eiichi

    2013-01-15

    Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.

  9. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    PubMed Central

    Hunt, Alison C.; Servín-González, Luis; Kelemen, Gabriella H.; Buttner, Mark J.

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed ΔbldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although ΔbldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein. PMID:15629942

  10. Travelers' Health: MERS in the Arabian Peninsula

    MedlinePlus

    ... Share Compartir Warning - Level 3, Avoid Nonessential Travel Alert - Level 2, Practice Enhanced Precautions Watch - Level 1, ... overseas. Clinician Information: Health care providers should be alert to patients who develop fever and symptoms of ...

  11. MERS in the U.S.

    MedlinePlus

    ... measures to prevent disease spread Provided guidance for flight crews, Emergency Medical Service (EMS) units at airports, ... began feeling unwell on May 1 during the flight from Jeddah, Saudi Arabia to London and continued ...

  12. Synthetic, Spectroscopic, and Electrochemical Studies of the Isomerically-Rich [M(CO)(2)(P(2)P')X](+/0) (M = Mn, Re; X = Cl, Br; P(2)P' = eta(3)-Ph(2)P(CH(2))(2)P(Ph)(CH(2))(2)PPh(2)) System: Structural Characterization of a Novel Pair of Diastereoisomers of cis,mer-Re(CO)(2)(P(2)P')Cl.

    PubMed

    Bond, Alan M.; Colton, Ray; Gable, Robert W.; Mackay, Maureen F.; Walter, Jacky N.

    1997-03-12

    Reaction of Mn(CO)(5)X (X = Cl, Br) with Ph(2)P(CH(2))(2)P(Ph)(CH(2))(2)PPh(2) (P(2)P') in refluxing xylene led to the formation of isomerically pure cis,mer-Mn(CO)(2)(eta(3)-P(2)P')X. Cyclic voltammograms in dichloromethane (0.1 M Bu(4)NPF(6)) show a reversible one-electron oxidation (process 1, E(1/2) = 0.142 V) to give cis,mer-[Mn(CO)(2)(P(2)P')X](+). However, in acetone (0.1 M Bu(4)NPF(6)) at room temperature, process 1 is not reversible and an additional redox process 4 (E(1/2) = 0.048 V) is observed. Process 4 is not observed at low temperatures, and at higher temperatures in acetone it merges with process 1 and also a new reversible redox couple (process 5, E(1/2) = -0.411 V) appears. A combination of electrolyses, chemical oxidation, and subsequent reduction, coupled with IR and (31)P NMR spectroscopies and electrospray mass spectrometry (ESMS), is used to show that processes 1, 4, and 5 are all associated with redox and interconversion reactions of different isomers of Mn(CO)(2)(P(2)P')X and [Mn(CO)(2)(P(2)P')X](+). Other irreversible processes due to oxidation of the different isomers of [Mn(CO)(2)(P(2)P')X](+) are observed at very positive potentials. Reaction between Re(CO)(5)X and P(2)P' in refluxing mesitylene gives a soluble product and a small amount of precipitate. The major soluble product was identified as cis,mer-Re(CO)(2)(P(2)P')X, and the oxidative chemistry is similar to that of the manganese analogues. The precipitate consists of five compounds, one of which was cis,mer-Re(CO)(2)(P(2)P')X. The new compounds A-D were identified as follows: A is cis,mer-{Re(CO)(2)(P(2)P')X}(2), a dimeric species with bridging P(2)P' ligands. The spectroscopic data for B indicated that it was a form of cis,mer-Re(CO)(2)(P(2)P')X, but not the same as the major product. Compound C is cis,fac-Re(CO)(2)(P(2)P')X, and compound D was shown to be fac-[Re(CO)(3)(P(2)P')]X. The crystal structures of cis,mer-Re(CO)(2)(P(2)P')Cl(I) and cis,mer-Re(CO)(2)(P(2)P')Cl(II) show

  13. MER vistas: ground-truth for Earth-based radar

    NASA Technical Reports Server (NTRS)

    Haldemann, Albert F.; Larsen, Kristopher W.; Jurgens, Raymond F.; Golombek, Matthew P.; Slade, Martin A.

    2004-01-01

    Earth-based delay-Doppler radar observations of Mars with four receiving stations were carried out during the Mars oppositions of 2001 and 2003 in support of Mars Exploration Rover landing site selection. This interferometric planetary radar technique has demonstrated radar mapping of Mars with a 5 km spatial resolution.

  14. Discovery of 12-mer peptides that bind to wood lignin.

    PubMed

    Yamaguchi, Asako; Isozaki, Katsuhiro; Nakamura, Masaharu; Takaya, Hikaru; Watanabe, Takashi

    2016-01-01

    Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin. PMID:26903196

  15. Antibody Response and Disease Severity in Healthcare Worker MERS Survivors

    PubMed Central

    Khalid, Imran; Ahmed, Waleed A.; Dada, Ashraf M.; Bayumi, Daniyah T.; Malic, Laut S.; Althawadi, Sahar; Ignacio, Kim; Alsalmi, Hanadi S.; Al-Abdely, Hail M.; Wali, Ghassan Y.; Qushmaq, Ismael A.; Alraddadi, Basem M.; Perlman, Stanley

    2016-01-01

    We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease. PMID:27192543

  16. Strategic analysis for the MER Cape Verde approach

    USGS Publications Warehouse

    Gaines, D.; Belluta, P.; Herman, J.; Hwang, P.; Mukai, R.; Porter, D.; Jones, B.; Wood, E.; Grotzinger, J.; Edgar, L.; Hayes, A.; Hare, T.; Squyres, S.

    2009-01-01

    The Mars Exploration Rover Opportunity has recently completed a two year campaign studying Victoria Crater. The campaign culminated in a close approach of Cape Verde in order to acquire high resolution imagery of the exposed stratigraphy in the cliff face. The close approach to Cape Verde provided significant challenges for every subsystem of the rover as the rover needed to traverse difficult, uncharacterised terrain and approach a cliff face with the potential of blocking out solar energy and communications with Earth. In this paper we describe the strategic analyses performed by the science and engineering teams so that we could successfully achieve the science objectives while keeping the rover safe. ??2009 IEEE.

  17. Discovery of 12-mer peptides that bind to wood lignin

    PubMed Central

    Yamaguchi, Asako; Isozaki, Katsuhiro; Nakamura, Masaharu; Takaya, Hikaru; Watanabe, Takashi

    2016-01-01

    Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin. PMID:26903196

  18. Strategic Analysis for the MER Cape Verde Approach

    NASA Technical Reports Server (NTRS)

    Gaines, Daniel; Belluta, Paolo; Herman, Jennifer; Hwang, Pauline; Mukai, Ryan; Porter, Dan; Jones, Byron; Wood, Eric; Grotzinger, John; Edgar, Lauren; Hayes, Alex; Hare, Trent; Squyres, Steve

    2009-01-01

    The Mars Exploration Rover Opportunity has recently completed a two year campaign studying Victoria Crater. The campaign culminated in a close approach of Cape Verde in order to acquire high resolution imagery of the exposed stratigraphy in the cliff face. The close approach to Cape Verde provided significant challenges for every subsystem of the rover as the rover needed to traverse difficult, uncharacterised terrain and approach a cliff face with the potential of blocking out solar energy and communications with Earth. In this paper we describe the strategic analyses performed by the science and engineering teams so that we could successfully achieve the science objectives while keeping the rover safe.

  19. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells

    PubMed Central

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M.

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450–463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  20. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    PubMed

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  1. Synthesis and Structure of [DB24C8)Na][Cd(SCN)3. Formation of a novel linear Cd...Cd...Cd chain with a mer-CdN3S3 coordination confirmation and new coiled [(DB24C8)Na]+ cation.

    PubMed

    Zhang, H; Wang, X; Zelmon, D E; Teo, B K

    2001-03-26

    We report herein a novel coordination solid, [(DB24C8)Na][Cd(SCN)3] (6) (DB24C8 denotes dibenzo-24-crown-8), which exhibits a new type of [Cd(SCN)3-]infinity chain with two unusual stereochemical characteristics: (1) a mer-CdN3S3 coordination and (2) a linear Cd chain with a Cd...Cd...Cd angle of 180 degrees. In addition, the [(DB24C8)Na]+ monocation adopts a new structural type-a coiled structure-for the combination of crown ether DB24C8 and alkali metal Na+. The title compound crystallizes in a monoclinic unit cell of C2/c space group symmetry with lattice parameters a = 16.110(8) A, b = 20.380(5) A, c = 11.01(1) A, beta = 119.87(3) degrees, and Z = 4. The arrangement of the [Cd(SCN)3-](infinity) chains in the crystal lattice in the title compound is approximately hexagonal, creating triangular channels which are filled with [(DB24C8)Na]+ monocations. It was previously reasoned by us that the coiled [(DB24C8)Na]+ monocation, which lacks inversion or mirror symmetries, should enhance the tendency for the formation of the noncentrosymmetric space group of the title crystal, making it a potential second-order nonlinear optical crystal. Interestingly, however, the title compound crystallizes in a centrosymmetric space group (C2/c) and gives rise to no second harmonic generation (SHG). Previously known [Cd(SCN)3-](infinity) chains adopt fac-CdN3S3 coordination and a zigzag Cd chain configuration with a Cd...Cd...Cd angle of 165 degrees. The zigzag chains can align in either parallel or antiparallel fashion, resulting in efficient or no SHG effects, respectively. The linear Cd.Cd.Cd chain configuration observed in the title compound, on the other hand, makes it indistinguishable between parallel and antiparallel alignments. It is concluded that, to ensure the formation of noncentrosymmetric space groups, it is necessary to employ optically pure chiral cations as spacers and/or controllers. Furthermore, to enhance the nonlinear optical responses, [Cd(SCN)3-]infinity

  2. DEVELOPMENT AND SELECTION OF TECHNOLOGIES FOR MERCURY MANAGEMENT ON U.S. DEPARTMENT OF ENERGY SITES: THE MER01-MER04 AND MERCURY SPECIATION DEMONSTRATIONS

    SciTech Connect

    Morris, Michael I.; Hulet, Greg A.

    2003-02-27

    The U.S. Department of Energy's (DOE's) Transuranic and Mixed Waste Focus Area (TMFA), funded from fiscal year (FY) 1996 though FY 2002, was tasked with finding solutions for the mixed waste treatment problems of the DOE complex. During TMFA's initial technical baseline development process, three of the top four technology deficiencies identified were the need for amalgamation, stabilization, and separation/removal technologies for the treatment of mercury-contaminated mixed waste. The Mercury Working Group (HgWG), a selected group of representatives from DOE sites with significant mercury waste inventories, assisted TMFA in soliciting, identifying, initiating, and managing efforts to address these areas. Solicitations and contract awards were made to the private sector to demonstrate both the amalgamation and stabilization processes using both actual mixed wastes and surrogate samples. The goal was to develop separation and removal processes that will meet DOE's needs. This paper discusses the technology selection process, development activities, and the accomplishments of TMFA through these various activities.

  3. Antibodies against MERS Coronavirus in Dromedary Camels, Kenya, 1992–2013

    PubMed Central

    Corman, Victor M.; Jores, Joerg; Meyer, Benjamin; Younan, Mario; Liljander, Anne; Said, Mohammed Y.; Gluecks, Ilona; Lattwein, Erik; Bosch, Berend-Jan; Drexler, Jan Felix; Bornstein, Set; Müller, Marcel A.

    2014-01-01

    Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance. PMID:25075637

  4. Diagnosing Vincent van Gogh, an expedition from the sources to the present "mer à boire".

    PubMed

    Voskuil, Piet

    2013-08-01

    The paintings and writings of Vincent van Gogh are widely admired for their great artistic value. This makes it interesting for doctors and patient groups to mold van Gogh's disease into a figurehead of their own specialty or illness. The recent article of ter Borg and Kasteleijn (2012) [1] in this Journal had a welcome approach by placing the diagnoses given in his lifetime in a historical and cultural context. In this article, the author will explore the diagnosis of epilepsy, adding more details without jumping quickly to conclusions. Apart from the information of eyewitnesses, special efforts are made to look critically at the medical sources as well as to investigate the original family chronicles. There is no easy access to that information. The Dutch vocabulary in the family notes made it tempting, for earlier scholars in this field, to easily link all kinds of attacks in family members to the original diagnosis of epilepsy. A part of the archives of the Willem Arntszhuis Utrecht describing the last days of Vincent's brother Theo, so far published only in Dutch (Voskuil, 2009 [16]), is included here. To integrate all this information, interdisciplinary research in a nonmutually excluding, but complementary, synthesis of today's knowledge is the most fruitful way to understand Vincent's behavior and its disturbances while continuing to admire his beautiful art.

  5. Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015.

    PubMed

    Kim, Dae-Won; Kim, You-Jin; Park, Sung Han; Yun, Mi-Ran; Yang, Jeong-Sun; Kang, Hae Ji; Han, Young Woo; Lee, Han Saem; Kim, Heui Man; Kim, Hak; Kim, A-Reum; Heo, Deok Rim; Kim, Su Jin; Jeon, Jun Ho; Park, Deokbum; Kim, Joo Ae; Cheong, Hyang-Min; Nam, Jeong-Gu; Kim, Kisoon; Kim, Sung Soon

    2016-01-01

    An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

  6. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...: Substances Limitation Condensation polymer of toluene sulfonamide and formaldehyde 0.15 pct maximum. (c... Sieve No. 10 is extracted with 250 mil of deionized water or reagent grade n-heptane at...

  7. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...: Substances Limitation Condensation polymer of toluene sulfonamide and formaldehyde 0.15 pct maximum. (c... Sieve No. 10 is extracted with 250 mil of deionized water or reagent grade n-heptane at...

  8. Distinct Igneous APXS Rock Compositions on Mars from Pathfinder, MER and MSL

    NASA Technical Reports Server (NTRS)

    Gellert, Ralf; Arvidson, Raymond; Clark, Benton, III; Ming, Douglas W.; Morris, Richard V.; Squyres, Steven W.; Yen, Albert S.

    2015-01-01

    The alpha particle x-ray spectrometer (APXS) on all four Mars Rovers returned geochemical data from about 1000 rocks and soils along the combined traverses of over 50 kilometers. Here we discuss rocks likely of igneous origin, which might represent source materials for the soils and sediments identified along the traverses. Adirondack-type basalts, abundant in the plains of Gusev Crater, are primitive, olivine bearing basalts. They resemble in composition the basaltic soils encountered at all landing sites, except the ubiquitous elevated S, Cl and Zn in soils. They have been postulated to represent closely the average Martian crust composition. The recently identified new Martian meteorite Black Beauty has similar overall geochemical composition, very distinct from the earlier established SNC meteorites. The rim of the Noachian crater Endeavour, predating the sulfate-bearing Burns formation at Meridiani Planum, also resembles closely the composition of Adirondack basalts. At Gale Crater, the MSL Curiosity rover identified a felsic rock type exemplified by the mugearitic float rock JakeM, which is widespread along the traverse at Gale. While a surprise at that time, possibly related more evolved, alkaline rocks had been previously identified on Mars. Spirit encountered the Wishstone rocks in the Columbia Hills with approx. 6% Na2O+K2O, 15 % Al2O3 and low 12% FeO. Pathfinder rocks with elevated K and Na and >50% SiO2 were postulated to be andesitic. Recently Opportunity encountered the rock JeanBaptisteCharbonneau with >15% Al2O3, >50% SiO2 and approx. 10% FeO. A common characteristic all these rocks is the very low abundance of Cr, Ni and Zn, and an Fe/Mn ratio of about 50, indicating an unaltered Fe mineralogy. Beside these likely igneous rock types, which occurred always in several rocks, a few unique rocks were encountered, e.g. Bounce Rock, a pyroxene-bearing ejecta rock fragment resembling the Shergottite EETA 79001B meteorite. The APXS data can be used to relate the findings of all 4 landing sites, constrain the water to rock ratio of sediments or imply source rock provenance. Beyond that the capability to quantify important volatile elements like P, S, Cl, and Br have provided new insights into the chemistry and the environment present during the formation of the sediments.

  9. Multispectral Properties of Fine-grained Materials at Gusev and Meridiani from MER/Pancam Observations

    NASA Astrophysics Data System (ADS)

    Bell, J. F.

    2005-12-01

    The Mars Exploration Rover Panoramic Camera (Pancam) instruments have acquired more than 41,000 and 37,000 multispectral images, respectively, from the rovers' landing sites and traverse paths within Gusev crater and Meridiani Planum as of early September 2005. The images have a resolution of from a few millimeters per pixel near the rover to a few meters per pixel for features near the horizon, and provide detailed information on the geology and morphology of the locations visited by the rovers. The 400 to 1000 nm spectral range of the color data also provides a limited amount of mineralogic information about iron-bearing phases, for selection of in situ analysis targets and comparison to and augmentation of more detailed compositional and mineralogic results from other rover instruments. These images include ten 360 degree panoramas acquired at Gusev and five 360 degree panoramas acquired at Meridiani. These panoramas were acquired using a subset of Pancam filters chosen to allow spectral parameterizations to be generated that provide maximal color unit discrimination within the available downlinked data volume and power constraints at the time of each observation. The images also include more than sixty limited color panoramas spanning at least 90 degrees of azimuth, and hundreds of 11-color multispectral spot observations of specific targets using all of the Pancam geology filters. Analysis of the large panoramas provides an assessment of the local-scale spectral diversity of each rover study site. Here we assess the nature of fine-grained materials at each site with results from the geographically-broad but spectrally-limited large panoramic color surveys, including the most recent data, augmented by much more narrowly-targeted full-color multispectral spot results. Fine-grained color units at Gusev include bright dust, bright and dark soils on planar surfaces (e.g., hollows) and in aeolian bedforms, dark dust created during Rock Abrasion Tool (RAT) grinding, and "white" subsurface soils in the Columbia Hills exposed by the rover wheels. Similar bright dust and dark soil units are seen at Meridiani, suggesting that they are a global unit. Other fine-grained units seen at Meridiani include several classes of the ubiquitous mm-scale spherules, mm- to sub-mm scale rock clasts, and bright dust generated by RAT grindings into the sulfur-rich sedimentary outcrop rocks.

  10. Characterization of Rock Types at Meridiani Planum, Mars using MER 13-Filter Pancam Spectra

    NASA Technical Reports Server (NTRS)

    Nuding, D. L.; Cohen, B. A.

    2009-01-01

    The Mars Exploration Rover Opportunity has traversed more than 13 km across Meridiani Planum, finding evidence of ancient aqueous environments that, in the past, may have been suitable for life. Meridiani bedrock along the rover traverse is a mixture in composition and bulk mineralogy between a sulfate-rich sedimentary rock and hematite spherules ("blueberries"). On top of the bedrock, numerous loose rocks exist. These rocks consist of both local bedrock and "cobbles" of foreign origin. The cobbles provide a window into lithologic diversity and a chance to understand other types of martian rocks and meteorites. This study was also an attempt to establish a method to expand upon those of Mini-TES to remotely identify rocks of interest to make efficient use of the rover s current resources.

  11. Initial Results from the MER Athena Science Investigation at Gusev Crater and Meridiani Planum

    NASA Astrophysics Data System (ADS)

    Squyres, S.

    2004-05-01

    The Mars Exploration Rover Spirit landed in Gusev Crater on January 4 (UTC), 2004. It was followed 21 days later by the rover Opportunity, which landed on Meridiani Planum. The landing site at Gusev crater lies on a flat, rock-strewn plain. The rock at Gusev that has been studied best to date has been named Adirondack. In its surface texture, Adirondack appears to be dense, fine-grained and sand-blasted. Three sets of measurements have been made on Adirondack with the full set of payload instruments: one of the natural rock surface, one of the same location after being brushed by the RAT, and one of the same location after removal of 2-3 mm of rock by the RAT. The concentration of presumably dust-borne elements like sulfur and chlorine diminished significantly with brushing, and diminished dramatically with grinding. All of the observations of Adirondack are consistent with it being an essentially unweathered olivine and magnetite-bearing, low-silica basalt. The only soil at Gusev that has been investigated in detail so far is one dominated by fairly coarse (100-300 micron) grains that have the appearance and behavior of well-cemented agglomerates. APXS spectra of this soil are similar to those of soils found at the Viking and Pathfinder sites. Mössbauer spectra show two ferrous doublets and a ferric doublet, with the stronger ferrous doublet assigned to olivine. Mini-TES spectra have been acquired for soils surrounding the the Spirit landing site, and show spectra nearly identical to globally averaged soil viewed by the TES instrument on Mars Global Surveyor. This includes identification of a small amount (a few percent) of carbonate. The landing site at Meridiani Planum lies inside an impact crater that is roughly 20 meters in diameter. The lander came to rest on soil that fills most of the crater. An outcrop of layered bedrock is exposed on the crater wall. The landing site was selected partly because coarse gray hematite was expected to be present on the basis of orbital data. Mini-TES data have confirmed the presence of this hematite in the soil. The soil within the crater has several components. Microscopic images of undisturbed surface soil show that one component is fine (~100 micron) sand. Mössbauer spectra of the sand show two ferrous doublets (one of them due to olivine), a ferric doublet, and a weak magnetic sextet. APXS and Mini-TES data on this sand are consistent with a composition dominated by basalt. Another component of the soil consists of coarse (several mm) granules. These range in shape from subangular to rounded to remarkably spherical. In some locations, granules have been pressed down into the soil by the impact of the landers airbags. At those locations the concentration of hematite as determined by Mini-TES is sharply reduced, suggesting that at least some of the granules are hematite-bearing. The bedrock outcrop is finely laminated, with typical layer thicknesses of only a few mm. The texture of the outcrop as viewed in miroscopic images suggests that it is fine-grained, with well-expressed structure that is revealed by varying degrees of mechanical abrasion of layers of varying induration. Initial APXS results on this fine-grained matrix indicate sulfur concentrations significantly higher than any observed elsewhere on Mars. Embedded within the outcrop and weathering out of it are highly spherical granules with diameters of several mm. The visible to near-IR spectral properties of these embedded spherical granules, as determined by Pancam, are distinctly different from those of the matrix in which they are embedded.

  12. Sequencing by hybridization with the generic 6-mer oligonucleotide microarray : an advanced scheme for data processing.

    SciTech Connect

    Chechetkin, V. R.; Turygin, A. Y.; Proudnikov, D. Y.; Prokopenko, D. V.; Kirillov, E. V.; Mirzabekov, A. D.; Biochip Technology Center; Russian Academy of Sciences

    2000-08-01

    DNA sequencing by hybridization was carried out with a microarray of all 4{sup 6} = 4,096 hexadeoxyribonucleotides (the generic microchip). The oligonucleotides immobilized in 100 x 100 x 20-{mu}m polyacrylamide gel pads of the generic microchip were hybridized with fluorescently labeled ssDNA, providing perfect and mismatched duplexes. Melting curves were measured in parallel for all microchip duplexes with a fluorescence microscope equipped with CCD camera. This allowed us to discriminate the perfect duplexes formed by the oligonucleotides, which are complementary to the target DNA. The DNA sequence was reconstructed by overlapping the complementary oligonucleotide probes. We developed a data processing scheme to heighten the discrimination of perfect duplexes from mismatched ones. The procedure was united with a reconstruction of the DNA sequence. The scheme includes the proper definition of a discriminant signal, preprocessing, and the variational principle for the sequence indicator function. The effectiveness of the procedure was confirmed by sequencing, proofreading, and nucleotide polymorphism (mutation) analysis of 13 DNA fragments from 31 to 70 nucleotides long.

  13. Blockade of MerTK Activation by AMPK Inhibits RPE Cell Phagocytosis.

    PubMed

    Qin, Suofu

    2016-01-01

    Timely removal of shed photoreceptor outer segments by retinal pigment epithelial cells (RPE) plays a key role in biological renewal of these highly peroxidizable structures and in maintenance of retina health. How environmental stress cause RPE cell dysfunction is undefined however. AMP-activated protein kinase (AMPK), a heterotrimer of a catalytic α subunit and regulatory β and γ subunits, maintains energy homeostasis by limiting energy utilization and/or promoting energy production when energy supply is compromised. Intriguingly, AMPK has been shown to be important in functions of RPE cells. In this mini-review, the role and mechanisms of AMPK in controlling RPE cell phagocytosis are discussed.

  14. Terrestrial Analogue Field Thermal Emission Spectroscopy: Applications to the MER Mini-TES

    NASA Astrophysics Data System (ADS)

    Greenhagen, B. T.; Kirkland, L. E.; Herr, K. C.

    2002-12-01

    The 2003 Mars Exploration Rover science strategy is to identify promising targets using the visible/near-infrared imaging Pancam and the thermal infrared spectrometer Mini-TES. The rover would then traverse to those targets for more detailed examination. Team members will select sites using target morphology and color from Pancam, and interpretations of the mineralogy using Mini-TES. This strategy requires low ambiguity, near real-time interpretations of Mini-TES data. Field spectrometer measurements from a rover perspective differ significantly from both laboratory and airborne measurements. Thus field testing using instrumentation similar to the Mini-TES is required to develop and test methods. We will discuss our field testing research toward that end, with a focus on smooth rock coatings. Researchers desire to detect and characterize smooth rock coatings on Mars, if present. In July 2002, we measured field data of a varnished desert pavement, using equipment that measures very similarly to the Mini-TES. Desert varnish may provide information on the environmental conditions, and interests exobiologists because it may be biologically mediated. Downwelling radiance can affect the spectral character by imparting the spectral character of the downwelling radiance onto the measured target spectrum. The contribution differs from the airborne, laboratory, and field perspectives, and with the surface texture. Downwelling radiance is the thermal energy radiated onto a target by all objects in the hemisphere, including surrounding materials and atmospheric gases and aerosols. Smooth (specular) targets reflect light at the angle of incidence (line-sight), while diffuse targets reflect downwelling radiance integrated from the entire hemisphere. Because even smooth rock coatings are not entirely smooth, they have both diffuse and specular components. Typically the diffuse downwelling component is measured using a high reflectance, rough-surfaced target with a known spectral signature. This is then used to compensate the geologic target for the downwelling component. This assumes that both the downwelling target and the geologic material have the same diffuse and line-site reflected downwelling radiance contributions. This works well for diffuse targets. However, smooth targets have a significant specular component, and the measurement and conversion protocols for these materials are currently poorly understood. The 2003 Mars rover does not carry a diffuse, high-reflectance target for Mini-TES. Thus the diffuse downwelling radiance will have to be estimated from line-sight sky measurements. Development and testing of this procedure and an improved understanding of the required measurement protocols and uncertainties will require field testing. We use Fourier transform infrared interferometers (M100). The M100 raster scans in two dimensions at 25 Hz, and it records the viewing angles with the data. The field of view is 20 or 8 mrad (Mini-TES) vs. 9 mrad (M100); spectral sampling interval 10 vs. 2 wavenumbers; spectral range 5-25 vs. 7.5-13.5 microns; and mast height 1.4 vs. 2-3 meters for the Mini-TES vs. M100, respectively.

  15. La conquête des mers siluriennes par les Spiriferida (Brachiopoda)

    NASA Astrophysics Data System (ADS)

    Gourvennec, Rémy

    1999-11-01

    The spiriferid brachiopods appeared in the Late Ordovician (Middle Ashgill) in southeastern Asia and then spread throughout the world during the Silurian. The strategies of expansion of the group and the changes in its diversity during this period are discussed here.

  16. Hematite at Meridiani Planum, Mars, Investigated by Simultaneous Fitting of MER Mossbauer Spectra

    NASA Technical Reports Server (NTRS)

    Fleischer, I.; Agresti, D. G.; Klingelhoefer, G.; Morris, Richard V.

    2010-01-01

    The Mars Exploration Rover Opportunity encountered sedimentary outcrop rocks at its landing site. Spherules with diameters in the millimeter range were found to weather from the outcrop rocks. With Opportunity s miniaturised M ssbauer spectrometer MIMOS II, hematite was detected in spherules and in the outcrop matrix [1,2]. Figure 1 shows the target Berry Bowl, where brushed outcrop and an accumulation of spherules could be investigated on sols 46 and 48 of Opportunity s mission. Hematite undergoes a transition from a weakly ferromagnetic above to an antiferromagnetic state below the Morin temperature (T(sub M) approx.265 K for chemically pure, crystalline hematite). The magnetic hyperfine splitting (B(sub hf)) shows a general decrease with increasing temperature and a drop of approx.0.8 T at T(sub M). The quadrupole splitting ((Delta)EQ) changes its sign at T(sub M), with negative values above and positive values below the transition. Crystallinity and particle size influence the magnitude and temperature dependence of the magnetic splitting and the quadrupole splitting [3].

  17. An Extended Kalman filter (EKF) for Mars Exploration Rover (MER) entry, descent, and landing reconstruction

    NASA Technical Reports Server (NTRS)

    Lisano, M. E.

    2003-01-01

    This paper describes the design and initial test results of an extended Kalman filter that has been developed at Jet Propulsion Laboratory (JPL) for post-flight reconstruction of the trajectory and attitude history of a spacecraft entering a planetary atmosphere and descending upon a parachute.

  18. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... temperature for 2 h.1 Minimum 10 pct solution viscosity at 25 °C (77 °F) is 10cP. 1 3. Acrylonitrile/styrene... average molecular weight, and solution viscosity, titled: “Determination of Residual Acrylonitrile and Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric...

  19. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... viscosity, titled: “Determination of Residual Acrylonitrile and Styrene Monomers-Gas Chromatographic... deionized water or reagent grade n-heptane at reflux temperature for 2 h.1 Minimum 10 pct solution viscosity... Copolymers,” and “Analytical Method for 10% Solution Viscosity of Tyril,” which are incorproated by...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... temperature for 2 h.1 Minimum 10 pct solution viscosity at 25 °C (77 °F) is 10cP. 1 3. Acrylonitrile/styrene... average molecular weight, and solution viscosity, titled: “Determination of Residual Acrylonitrile and Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric...

  1. Preliminary epidemiologic assessment of MERS-CoV outbreak in South Korea, May–June 2015

    PubMed Central

    Cowling, Benjamin J; Park, Minah; Fang, Vicky J; Wu, Peng; Leung, Gabriel M; Wu, Joseph T

    2015-01-01

    South Korea is experiencing the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula, with 166 laboratory-confirmed cases, including 24 deaths as of 19 June 2015. We estimated that the mean incubation period was 6.7 days and the mean serial interval 12.6 days. We found it unlikely that infectiousness precedes symptom onset. Based on currently available data, we predict an overall case fatality risk of 21.3% (95% credible interval: 14%–31%). PMID:26132767

  2. 76 FR 2920 - Notice of Correction to Notice of Realty Action: Competitive Online Auction of Public Lands in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    .... The individual patents, when issued, will contain a mineral reservation to the United States for oil, gas, sodium, potassium, and all saleable minerals. FOR FURTHER INFORMATION CONTACT: Manuela Johnson...

  3. Large deviation approach to the generalized random energy model

    NASA Astrophysics Data System (ADS)

    Dorlas, T. C.; Dukes, W. M. B.

    2002-05-01

    The generalized random energy model is a generalization of the random energy model introduced by Derrida to mimic the ultrametric structure of the Parisi solution of the Sherrington-Kirkpatrick model of a spin glass. It was solved exactly in two special cases by Derrida and Gardner. A complete solution for the thermodynamics in the general case was given by Capocaccia et al. Here we use large deviation theory to analyse the model in a very straightforward way. We also show that the variational expression for the free energy can be evaluated easily using the Cauchy-Schwarz inequality.

  4. CD8 T-cell responses against the immunodominant Theileria parva peptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes.

    PubMed

    Connelley, Timothy K; Li, Xiaoying; MacHugh, Niall; Colau, Didier; Graham, Simon P; van der Bruggen, Pierre; Taracha, Evans L; Gill, Andy; Morrison, William Ivan

    2016-10-01

    Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249-59 and Tp1214-224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide-MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298-106 ), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249-59 -reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250-59 represents a distinct epitope and that tetramers produced with Tp50-59 and Tp49-59 show no cross-reactivity. The Tp249-59 and Tp250-59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide-MHC I complexes adopt structurally different conformations and Tcell receptor β sequence analysis showed that Tp249-59 and Tp250-59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249-59 and Tp250-59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214-224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249-59 epitope response was generally more dominant than the Tp250-59 response and confirmed that the Tp298-106 response was subdominant.

  5. CD8 T-cell responses against the immunodominant Theileria parva peptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes.

    PubMed

    Connelley, Timothy K; Li, Xiaoying; MacHugh, Niall; Colau, Didier; Graham, Simon P; van der Bruggen, Pierre; Taracha, Evans L; Gill, Andy; Morrison, William Ivan

    2016-10-01

    Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249-59 and Tp1214-224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide-MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298-106 ), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249-59 -reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250-59 represents a distinct epitope and that tetramers produced with Tp50-59 and Tp49-59 show no cross-reactivity. The Tp249-59 and Tp250-59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide-MHC I complexes adopt structurally different conformations and Tcell receptor β sequence analysis showed that Tp249-59 and Tp250-59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249-59 and Tp250-59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214-224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249-59 epitope response was generally more dominant than the Tp250-59 response and confirmed that the Tp298-106 response was subdominant. PMID:27317384

  6. Proglacial sediment supply and channel evolution of the Arveyron of the Mer de Glace since the early 20th c.

    NASA Astrophysics Data System (ADS)

    Berthet, Johan; Astrade, Laurent

    2015-04-01

    Glacier retreat in the Alps, from the end of the Little Ice Age (LIA) to now, has released large sediment-covered areas. Those rock debris are potential massive sediment supply which could increase proglacial stream activity and worry river managers and authorities. However, because of the ice shrinkage, proglacial hydrographic pattern in the headwater is evolving. The connexion between morainic sediments and proglacial streams is thus moving. The goal of our study is to understand the evolution of sediment sources and their level of connectivity with the proglacial streams located on the French side of the Mont-Blanc massif (Chamonix Valley). We have used the Connectivity Index (IC) wich is a geostatistic method based on lidar DEM for assessing the probability for the sediment- covered areas to be connected to a certain outlet. Then, we have kept only the IC which could be supplied by the potential glacial meltwater with the LIA and 2008 glacier extension. Unfortunately, available lidar DEM does not cover the entire study area. Nevertheless, it is sufficient to get partial or full results on different glacier types: valley glacier, cirque glacier, etc. Results are checked using the mapping of - active or not - gullies and through the analyse of the large historical picture collection available in which it is possible to identify the past active sediment sources. Results show some explicit processes such as the contraction of the sediment sources inside morainic vallums whereas the outer moraine side was active during the LIA. Generally, results suggest a disconnection trend between sediment sources and the trunk valley. These results seem to be confirmed by a general tendency of decreasing activity of proglacial streams which is observed in the Chamonix valley. Even if this method shows some bias, it represents an interesting semi-quantitative and geographic approach to assess past proglacial sediment sources thanks to glacier extensions. It is also possible to imagine other applications using this method such as isolated the IC from the lithology or the nature of sediment sources.

  7. 1.25 Å resolution structure of an RNA 20-mer that binds to the TREX2 complex.

    PubMed

    Valkov, Eugene; Stewart, Murray

    2015-10-01

    The 1.25 Å resolution H32:R crystal structure of a 20 nt ribonucleotide that binds to the TREX-2 complex with high affinity shows a double-stranded RNA duplex arranged along a crystallographic 31 axis in which the antiparallel chains overlap by 18 nucleotides and are related by a crystallographic twofold axis. The duplex shows C-A, U-U and C-C noncanonical base pairings together with canonical Watson-Crick A-U and G-C pairs and a G-U wobble.

  8. Single molecule analysis of DNA wrapping and looping by a circular 14mer wheel of the bacteriophage 186 CI repressor.

    PubMed

    Wang, Haowei; Dodd, Ian B; Dunlap, David D; Shearwin, Keith E; Finzi, Laura

    2013-06-01

    The lytic-lysogenic decision in bacteriophage 186 is governed by the 186 CI repressor protein in a unique way. The 186 CI is proposed to form a wheel-like oligomer that can mediate either wrapped or looped nucleoprotein complexes to provide the cooperative and competitive interactions needed for regulation. Although consistent with structural, biochemical and gene expression data, many aspects of this model are based on inference. Here, we use atomic force microscopy (AFM) to reveal the various predicted wrapped and looped species, and new ones, for CI regulation of lytic and lysogenic transcription. Automated AFM analysis showed CI particles of the predicted dimensions on the DNA, with CI multimerization favoured by DNA binding. Measurement of the length of the wrapped DNA segments indicated that CI may move on the DNA, wrapping or releasing DNA on either side of the wheel. Tethered particle motion experiments were consistent with wrapping and looping of DNA by CI in solution, where in contrast to λ repressor, the looped species were exceptionally stable. The CI regulatory system provides an intriguing comparison with that of nucleosomes, which share the ability to wrap and release similar sized segments of DNA. PMID:23620280

  9. mer-Triaqua­(1,10-phenanthroline-κ2 N,N′)(sulfato-κO)magnesium(II)

    PubMed Central

    Zhu, Ling; Huang, Jing; Han, Si-Ying; An, Zhe

    2008-01-01

    In the title compound, [Mg(SO4)(C12H8N2)(H2O)3], the MgII centre exhibits a slightly distorted octa­hedral coordination environment defined by two N atoms from a 1,10-phenanthroline mol­ecule, one O atom from a sulfate dianion and three meridionally arranged O atoms from coordinated water mol­ecules. The crystal structure involves intra- and intermolecular O—H⋯O hydrogen bonds. PMID:21202220

  10. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as...), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, or available for... Paint Branch Pkwy., College Park, MD 20740, or available for inspection at the National Archives...

  11. Comparing Apollo and Mars Exploration Rover (MER) Operations Paradigms for Human Exploration During NASA Desert-Rats Science Operations

    NASA Technical Reports Server (NTRS)

    Yingst, R. A.; Cohen, B. A.; Ming, D. W.; Eppler, D. B.

    2011-01-01

    NASA's Desert Research and Technology Studies (D-RATS) field test is one of several analog tests that NASA conducts each year to combine operations development, technology advances and science under planetary surface conditions. The D-RATS focus is testing preliminary operational concepts for extravehicular activity (EVA) systems in the field using simulated surface operations and EVA hardware and procedures. For 2010 hardware included the Space Exploration Vehicles, Habitat Demonstration Units, Tri-ATHLETE, and a suite of new geology sample collection tools, including a self-contained GeoLab glove box for conducting in-field analysis of various collected rock samples. The D-RATS activities develop technical skills and experience for the mission planners, engineers, scientists, technicians, and astronauts responsible for realizing the goals of exploring planetary surfaces.

  12. In vivo quantifying molecular specificity of Cy5.5-labeled cyclic 9-mer peptide probe with dynamic fluorescence imaging

    PubMed Central

    Dai, Yunpeng; Yin, Jipeng; Huang, Yu; Chen, Xueli; Wang, Guodong; Liu, Yajun; Zhang, Xianghan; Nie, Yongzhan; Wu, Kaichun; Liang, Jimin

    2016-01-01

    We quantified molecular specificity of Cy5.5-GX1 in vivo with dynamic fluorescence imaging to better understand its kinetic properties. According to whether or not free GX1 was injected and when it was injected, twelve of BGC-823 xenografted mice were randomly divided into three groups and underwent a 60 minute dynamic fluorescence scanning. Combined with a principal-component analysis, the binding potential (Bp) of the probe was determined by both Logan graphical analysis with reference tissue model (GARTM) and Lammertsma simplified reference tissue model (SRTM). The sum of the pharmacokinetic rate constants (SKRC) was quantified by the Gurfinkel exponential model (GEXPM). Cy5.5-GX1 specifically targeted tumor both in vitro and in vivo. We obtained similar quantification results of Bp (GARTM Bp = 0.582 ± 0.2655, SRTM Bp = 0.618 ± 0.2923), and obtained a good linear relation between the Bp value and the SKRC value. Our results indicate that the SKRC value is more suitable for an early-stage kinetic data analysis, and the Bp value depicts kinetic characteristics under the equilibrium state. Dynamic fluorescence imaging in conjunction with various kinetic models are optimal tools to quantify molecular specificity of the Cy5.5-GX1 probe in vivo. PMID:27446643

  13. Rigorous Photogrammetric Processing of HiRISE Stereo Images for Topographic and Geomorphologic Analysis at MER landing sites

    NASA Astrophysics Data System (ADS)

    Li, R.; di, K.; Hwangbo, J.; Chen, Y.

    2007-12-01

    High-precision topographic information is critical to Mars surface exploration. Such information can be derived from both orbital and ground rover data. The availability of HiRISE stereo images makes a great progress in high resolution imaging and topographic and morphological information derivation. This presentation gives the necessary rigorous photogrammetric model for HiRISE stereo image processing and results achieved at the Mars Exploration Rover mission sites. HiRISE is a push-broom imaging sensor. For short segments of the orbital trajectory, 2nd-order polynomials can be used to model change in the exterior orientation (EO) parameters with respect to time. Since all of the 14 CCD lines (10 red, 2 blue-green and 2 NIR) share the same EO parameters at a specific time, only one set of polynomial parameters is needed to model the EO parameters for all the CCD arrays. The orbit's initial position and pointing angles are provided in the SPICE kernels. For any given ephemeris time, the EO parameters can be retrieved by interpolating the spacecraft's trajectory and pointing vectors. Based on the developed rigorous sensor model, we have developed a method for bundle adjustment (BA) of HiRISE stereo images that removes or reduces measurement inconsistency and improves mapping precision. We have also developed a hierarchical stereo matching process. Based on the original images, an image pyramid with 5 levels is constructed by sub-sampling of each previous level. Interest points are generated by Foerstner operator at every image scale. Matching starts from the images of the lowest resolution; results are transferred to the next higher level, with more interest points being extracted and matched. After matching the highest resolution images, evenly distributed matched interest points are selected as tie points between the stereo images. In the end, grid points (4-pixel spacing) are defined and matched to generate a DTM of the terrain. Using the HiRISE images TRA_000873_1780 and PSP_001414_1780 of Victoria Crater, 136 evenly distributed tie points and 135 check points were automatically selected for BA. Before BA, the mean residual in the along- track direction was 24.6 pixels with a standard deviation of 0.77 pixel, and the mean residual in the cross-track direction was 0.017 pixel with a standard deviation of 0.23 pixel. After BA, the mean residual in the along-track and cross-track directions are 0.30 pixel and 0.0047 pixel, respectively, with standard deviations of 0.37 pixel and 0.024 pixel. This improved precision ensures the high quality of topographic and morphological information to be derived. Currently, we are processing a stereo pair of HiRISE images that cover Husband Hill and the Home Plate area. The presentation should provide more detailed information and results.

  14. In vivo quantifying molecular specificity of Cy5.5-labeled cyclic 9-mer peptide probe with dynamic fluorescence imaging.

    PubMed

    Dai, Yunpeng; Yin, Jipeng; Huang, Yu; Chen, Xueli; Wang, Guodong; Liu, Yajun; Zhang, Xianghan; Nie, Yongzhan; Wu, Kaichun; Liang, Jimin

    2016-04-01

    We quantified molecular specificity of Cy5.5-GX1 in vivo with dynamic fluorescence imaging to better understand its kinetic properties. According to whether or not free GX1 was injected and when it was injected, twelve of BGC-823 xenografted mice were randomly divided into three groups and underwent a 60 minute dynamic fluorescence scanning. Combined with a principal-component analysis, the binding potential (Bp) of the probe was determined by both Logan graphical analysis with reference tissue model (GARTM) and Lammertsma simplified reference tissue model (SRTM). The sum of the pharmacokinetic rate constants (SKRC) was quantified by the Gurfinkel exponential model (GEXPM). Cy5.5-GX1 specifically targeted tumor both in vitro and in vivo. We obtained similar quantification results of Bp (GARTM Bp = 0.582 ± 0.2655, SRTM Bp = 0.618 ± 0.2923), and obtained a good linear relation between the Bp value and the SKRC value. Our results indicate that the SKRC value is more suitable for an early-stage kinetic data analysis, and the Bp value depicts kinetic characteristics under the equilibrium state. Dynamic fluorescence imaging in conjunction with various kinetic models are optimal tools to quantify molecular specificity of the Cy5.5-GX1 probe in vivo. PMID:27446643

  15. Estimation of the whitefly Bemisia tabaci genome size based on k-mer and flow cytometry analyses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whiteflies, Bemisia tabaci (Hemiptera: Aleyrodidae), are one of the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 500 crop plants worldwide and inflict severe economic losses, mainly through the transmission of pathogenic viruses. Surprisingl...

  16. Genome Sequence of Photobacterium halotolerans MELD1, with Mercury Reductase (merA), Isolated from Phragmites australis.

    PubMed

    Mathew, Dony Chacko; Mathew, Gincy Marina; Gicana, Ronnie Gicaraya; Huang, Chieh-Chen

    2015-06-04

    Here, we present the whole-genome sequence of Photobacterium halotolerans strain, MELD1, isolated from the roots of a terrestrial plant Phragmites australis grown in soil heavily contaminated with mercury and dioxin. The genome provides further insight into the adaptation of bacteria to the toxic environment from where it was isolated.

  17. Aporphine alkaloids from the leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and their cytotoxic and antibacterial activities.

    PubMed

    Omar, Hanita; Hashim, Najihah Mohd; Zajmi, Asdren; Nordin, Noraziah; Abdelwahab, Siddiq Ibrahim; Azizan, Ainnul Hamidah Syahadah; Hadi, A Hamid A; Ali, Hapipah Mohd

    2013-07-29

    The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC₅₀ values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC₅₀ values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3.

  18. 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

    ... and all documents entered into this docket is available on the World Wide Web at http://www... published on April 11, 2000 (65 FR 19477-78). By Order of the Maritime Administrator. Dated: August 9,...

  19. Strength and deformability of light-toned layered deposits observed by MER Opportunity: Eagle to Erebus craters, Mars

    NASA Astrophysics Data System (ADS)

    Okubo, Chris H.

    2007-10-01

    Quantifying host rock deformation is vital to understanding the geologic evolution and productivity of subsurface fluid reservoirs. In support of on-going characterization of fracture controlled fluid flow through the light-toned layered deposits on Mars, key parameters of strength and deformability are derived from Microscopic Imager and Rock Abrasion Tool data collected by the Mars Exploration Rover Opportunity in Meridiani Planum. Analysis of 21 targets of light-toned layered deposits yields a median apparent porosity of 0.25. Additional physical parameters for each target are derived from these porosity measurements. The median value of unconfined compressive strength is 11.23 MPa, Young's modulus is 1.86 GPa, and the brittle-ductile transition pressure is 8.77 MPa.

  20. Field Reconnaissance Geologic Mapping of the Columbia Hills, Mars: Results from MER Spirit and MRO HiRISE Observations

    USGS Publications Warehouse

    Crumpler, L.S.; Arvidson, R. E.; Squyres, S. W.; McCoy, T.; Yingst, A.; Ruff, S.; Farrand, W.; McSween, Y.; Powell, M.; Ming, D. W.; Morris, R.V.; Bell, J.F.; Grant, J.; Greeley, R.; DesMarais, D.; Schmidt, M.; Cabrol, N.A.; Haldemann, A.; Lewis, Kevin W.; Wang, A.E.; Schroder, C.; Blaney, D.; Cohen, B.; Yen, A.; Farmer, J.; Gellert, Ralf; Guinness, E.A.; Herkenhoff, K. E.; Johnson, J. R.; Klingelhofer, G.; McEwen, A.; Rice, J. W.; Rice, M.; deSouza, P.; Hurowitz, J.

    2011-01-01

    Chemical, mineralogic, and lithologic ground truth was acquired for the first time on Mars in terrain units mapped using orbital Mars Reconnaissance Orbiter's High Resolution Imaging Science Experiment (MRO HiRISE) image data. Examination of several dozen outcrops shows that Mars is geologically complex at meter length scales, the record of its geologic history is well exposed, stratigraphic units may be identified and correlated across significant areas on the ground, and outcrops and geologic relationships between materials may be analyzed with techniques commonly employed in terrestrial field geology. Despite their burial during the course of Martian geologic time by widespread epiclastic materials, mobile fines, and fall deposits, the selective exhumation of deep and well-preserved geologic units has exposed undisturbed outcrops, stratigraphic sections, and structural information much as they are preserved and exposed on Earth. A rich geologic record awaits skilled future field investigators on Mars. The correlation of ground observations and orbital images enables construction of a corresponding geologic reconnaissance map. Most of the outcrops visited are interpreted to be pyroclastic, impactite, and epiclastic deposits overlying an unexposed substrate, probably related to a modified Gusev crater central peak. Fluids have altered chemistry and mineralogy of these protoliths in degrees that vary substantially within the same map unit. Examination of the rocks exposed above and below the major unconformity between the plains lavas and the Columbia Hills directly confirms the general conclusion from remote sensing in previous studies over past years that the early history of Mars was a time of more intense deposition and modification of the surface. Although the availability of fluids and the chemical and mineral activity declined from this early period, significant later volcanism and fluid convection enabled additional, if localized, chemical activity.

  1. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... viscosity of the matrix copolymer in butyrolactone is not less than 0.5 deciliter/gram at 35 °C, as determined by the method titled “Molecular Weight of Matrix Copolymer by Solution Viscosity,” which is... copolymer articles is not more than 11 ppm as determined by a gas chromatographic method...

  2. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... viscosity of the matrix copolymer in butyrolactone is not less than 0.5 deciliter/gram at 35 °C, as determined by the method titled “Molecular Weight of Matrix Copolymer by Solution Viscosity,” which is... copolymer articles is not more than 11 ppm as determined by a gas chromatographic method...

  3. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... viscosity of the matrix copolymer in butyrolactone is not less than 0.5 deciliter/gram at 35 °C, as determined by the method titled “Molecular Weight of Matrix Copolymer by Solution Viscosity,” which is... copolymer articles is not more than 11 ppm as determined by a gas chromatographic method...

  4. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... viscosity of the matrix copolymer in butyrolactone is not less than 0.5 deciliter/gram at 35 °C, as determined by the method titled “Molecular Weight of Matrix Copolymer by Solution Viscosity,” which is... copolymer articles is not more than 11 ppm as determined by a gas chromatographic method...

  5. Local initiatives: USAID / Peru supports national legislation on domestic violence.

    PubMed

    1997-01-01

    This brief article describes the activities of USAID-funded groups that promote gender equality and the protection of women and children against domestic violence in Peru. The Peruvian legislature passed Public Law 26260 in 1993, which addresses the issue of domestic violence. The Movimiento Mujers Peruanas Manuela Ramos received support from USAID to develop a registration, protection, redress, and referral system for women who suffer domestic violence. A campaign was conducted that used leaflets and radio and television to educate women about the new law and their rights under it. USAID also supported the Ombudsman's Office for Women. This office instituted a national study on domestic violence that will provide a database for monitoring reductions in domestic violence expected from the new law and the campaign. ReproSalud has a reproductive health project that USAID is funding. This group as well as 18 other groups function under an umbrella group, the Manuela Ramos. The target is poor women living in disadvantaged rural and urban areas, who are at greater risk of domestic violence. Manuela Ramos conducted participatory, qualitative research that helps women rank their reproductive health needs. All 18 organizations found domestic violence to be a reproductive health problem. One organization identified it as the most serious problem, and one that contributes to complications during delivery. Manuela Ramos works to make men more aware of the negative impact that domestic violence has on women.

  6. Solvent–amino acid interaction energies in three-dimensional-lattice Monte Carlo simulations of a model 27-mer protein: Folding thermodynamics and kinetics

    PubMed Central

    Leonhard, Kai; Prausnitz, John M.; Radke, Clayton J.

    2004-01-01

    Amino acid residue–solvent interactions are required for lattice Monte Carlo simulations of model proteins in water. In this study, we propose an interaction-energy scale that is based on the interaction scale by Miyazawa and Jernigan. It permits systematic variation of the amino acid–solvent interactions by introducing a contrast parameter for the hydrophobicity, Cs, and a mean attraction parameter for the amino acids, ω. Changes in the interaction energies strongly affect many protein properties. We present an optimized energy parameter set for best representing realistic behavior typical for many proteins (fast folding and high cooperativity for single chains). Our optimal parameters feature a much weaker hydrophobicity contrast and mean attraction than does the original interaction scale. The proposed interaction scale is designed for calculating the behavior of proteins in bulk and at interfaces as a function of solvent characteristics, as well as protein size and sequence. PMID:14739322

  7. X-ray Crystal Structure of a Locked Nucleic Acid (LNA) Duplex Composed of a Palindromic 10-mer DNA Strand Containing One LNA Thymine Monomer

    SciTech Connect

    Egli, M.; Minasov, G.; Teplova, M.; Kumar, R.; Wengel, J.

    2010-03-05

    Locked nucleic acid (LNA), a recently introduced nucleic acid analogue with a bicyclic 2'-O,4'-C-methylene linked furanose sugar, exhibits enhanced affinities for DNA and RNA relative to the corresponding oligodeoxyribonucleotides and oligoribonucleotides; we report the first crystal structure of an LNA unit incorporated in an oligonucleotide duplex. The structure at 1.4 {angstrom} resolution of the DNA-LNA decamer duplex with one LNA thymine monomer per strand provides a detailed view of the conformation and hydration of locked nucleic acid residues in a duplex A-form. Our study provides a first look at the conformational properties of LNA in a crystal structure at relatively high resolution. The main characteristics of the structure are the standard A-type conformation induced by LNA residues and the capacity of the 2'-oxygen that is part of the bicyclic sugar framework to engage in a least two hydrogen bonds to water molecules. Circular dichroism spectra (CD) of LNA-LNA duplexes in solution indicated that such duplexes appear to adopt a conformation that closely resembles the A-form geometry of RNA-RNA duplexes. However, these spectra also manifested subtle differences between the two species (data not shown). The present analysis of a duplex with only a single LNA residue per strand does not provide any insight into potential conformational differences between LNA and RNA duplexes. Attempts to determine a crystal structure of a completely modified LNA-LNA duplex are underway.

  8. Role of the semi-conserved histidine residue in the light-sensing domain of LitR, a MerR-type photosensory transcriptional regulator.

    PubMed

    Takano, Hideaki; Mise, Kou; Maruyama, Takafumi; Hagiwara, Kenta; Ueda, Kenji

    2016-08-01

    The LitR/CarH protein family transcriptional regulator is a new type of photoreceptor based on the function of adenosyl B12 (AdoB12) as a light-sensitive ligand. Here, we studied a semi-conserved histidine residue (His132) in the light-sensing (AdoB12-binding) domain at the C-terminus of LitR from a thermophilic Gram-negative bacterium, Thermus thermophilus HB27. The in vivo mutation of His132 within LitR caused a reduction in the rate of carotenoid production in response to illumination. BIAcore analysis revealed that the illuminated-LitRH132A possesses high DNA-binding activity compared to the wild-type protein. The subunit structure analysis showed that LitRH132A performed an incomplete subunit dissociation. The ability of LitRH132A to associate with AdoB12 was reduced compared with that of the wild-type protein in an equilibration dialysis experiment. Overall, these results suggest that His132 of LitR is involved in the association with AdoB12 as well as the light-sensitive DNA-binding activity based on oligomer dissociation. PMID:27283316

  9. Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites.

    PubMed

    Munch, Henrik K; Nygaard, Jesper; Christensen, Niels Johan; Engelbrekt, Christian; Østergaard, Mads; Porsgaard, Trine; Hoeg-Jensen, Thomas; Zhang, Jingdong; Arleth, Lise; Thulstrup, Peter W; Jensen, Knud J

    2016-02-12

    Controlled self-assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal-ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2'-bipyridine (bipy) ligand to HI, yielding HI-bipy, enabled Zn(II)-binding hexamers to SA into trimers of hexamers, [[HI-bipy]6]3, driven by octahedral coordination to a Fe(II)  ion. The structures were studied in solution by small-angle X-ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe(II) than Zn(II)  ions, enabling control of the hexamer formation with Zn(II) and the formation of trimers of hexamers with Fe(II)  ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine. PMID:26762534

  10. Sterically (un)encumbered mer-tridentate N-heterocyclic carbene complexes of titanium(iv) for the copolymerization of cyclohexene oxide with CO2.

    PubMed

    Hessevik, Julie; Lalrempuia, Ralte; Nsiri, Hajar; Törnroos, Karl W; Jensen, Vidar R; Le Roux, Erwan

    2016-10-01

    Titanium(iv) complexes bearing an unsubstituted tridentate bis(phenolate) N-heterocyclic carbene (NHC) were synthesized and structurally identified. While sterically unencumbered NHC-Ti(iv) complexes bearing chloro and alkoxy co-ligands tend to dimerize in solution and in solid-state, the use of a bulky aryloxy as co-ligand favors the monomeric species. Upon activation by onium salts, all these complexes were found to be highly selective towards the copolymerization of cyclohexene oxide (CHO) with CO2 under mild conditions (PCO2 < 1 bar), albeit the sterically unencumbered NHC-Ti(iv) complexes are less stable and active than their structural analogues bearing bulkier substituents.

  11. Transposon tagging of a male-sterility, female-sterility gene, St8, revealed that the meiotic MER3 DNA helicase activity is essential for fertility in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion fr...

  12. Weathering of Basaltic Rocks from the Gusev Plains up into the Columbia Hills from the Perspective of the MER Mossbauer Spectrometer

    NASA Technical Reports Server (NTRS)

    Schroeder, C.; Klingelhoefer, G.; Morris, R. V.; Rodionov, D. S.; deSouza, P. A.; Ming, D. W.; Yen, A. S.; Gellert, R.; Bell, J. F., III

    2005-01-01

    Rocks on the ejecta blanket of Bonneville crater and along Spirit s traverse over the Gusev plains towards the Columbia Hills are angular and strewn across the surface. They have a basaltic composition [1,2], and their Mossbauer spectra are dominated by an olivine doublet [1]. The ubiquitous presence of abundant olivine in rocks and in surrounding soil suggests that physical rather than chemical weathering processes currently dominate the plains at Gusev crater [1]. However, MB spectra of rocks and outcrops in the Columbia Hills suggest more aggressive alteration processes have occurred. Ascending into the hills, Spirit encountered outcrop and rocks exhibiting layered structures. Some scattered rocks at the foot of the Columbia Hills appeared "rotten" or highly altered by physical and/or chemical processes (fig. 1). Mossbauer spectra of those rocks show a decrease in olivine accompanied by an increase in the Fe-oxides magnetite, hematite, and nanophase Fe3+ -oxides (fig. 2), suggesting that chemical weathering processes in the presence of water have altered these rocks and outcrops.

  13. Exploration of structure-activity relationships at the two C-terminal residues of potent 11mer Glucagon-Like Peptide-1 receptor agonist peptides via parallel synthesis.

    PubMed

    Haque, Tasir S; Martinez, Rogelio L; Lee, Ving G; Riexinger, Douglas G; Lei, Ming; Feng, Ming; Koplowitz, Barry; Mapelli, Claudio; Cooper, Christopher B; Zhang, Ge; Huang, Christine; Ewing, William R; Krupinski, John

    2010-07-01

    We report the identification of potent agonists of the Glucagon-Like Peptide-1 receptor (GLP-1R) via evaluation of two positional scanning libraries and a two-dimensional focused library, synthesized in part on SynPhase Lanterns. These compounds are 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of biphenylalanine (Bip) at the two C-terminal positions. Typical activities of the most potent peptides in this class are in the picomolar range in an in vitro functional assay using human GLP-1 receptor.

  14. Identification of potent 11mer glucagon-like peptide-1 receptor agonist peptides with novel C-terminal amino acids: Homohomophenylalanine analogs.

    PubMed

    Haque, Tasir S; Lee, Ving G; Riexinger, Douglas; Lei, Ming; Malmstrom, Sarah; Xin, Li; Han, Songping; Mapelli, Claudio; Cooper, Christopher B; Zhang, Ge; Ewing, William R; Krupinski, John

    2010-05-01

    We report the identification of potent agonists of the Glucagon-Like Peptide-1 Receptor (GLP-1R). These compounds are short, 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of homohomophenylalanine (hhPhe) at the C-terminal position. Typically the functional activity of the more potent peptides in this class is in the low picomolar range in an in vitro cAMP assay, with one example demonstrating excellent in vivo activity in an ob/ob mouse model of diabetes.

  15. IAU Colloquium on UV and X-ray Spectroscopy of Astrophysical and Laboratory Plasmas, 102nd, Beaulieu-sur-Mer, France, Sept. 9-11, 1987, Proceedings

    NASA Astrophysics Data System (ADS)

    Bely-Dubau, F.; Faucher, P.

    1988-03-01

    The present conference discusses the solar physics results of Spacelab 2, spectroscopic methods for electron density determination, microcalorimeters for X-ray spectroscopy, spectral observations of the XUV astronomical background radiation, XUV lasers, spectroscopic diagnoses of tokamaks, nonthermal X-ray spectra from a tokamak, and space- and time-resolved plasma diagnostics in laser-produced plasmas. Also discussed are the application in atomic physics of coupled differential equations, the interpretation of unresolved hyperfine and/or Zeeman structures in stellar spectra, atomic physics for hot plasmas, IUE satellite-based UV astronomy contributions, plasma shifts of ion lines, and the use of Ti, Si, C, Be, and LiF in soft X-ray optics.

  16. Cyanide-bridged Fe(III)-Mn(III) bimetallic complexes with dimeric and chain structures constructed from a newly made mer-Fe tricyanide: structures and magnetic properties.

    PubMed

    Kim, Jae Il; Kwak, Hyun Young; Yoon, Jung Hee; Ryu, Dae Won; Yoo, In Young; Yang, Namgeun; Cho, Beong Ki; Park, Je-Geun; Lee, Hyosug; Hong, Chang Seop

    2009-04-01

    Four cyanide-linked Fe(III)-Mn(III) complexes were prepared by reacting Mn Schiff bases with a new molecular precursor (PPh(4))[Fe(qcq)(CN)(3)] [1; qcq = 8-(2-quinolinecarboxamido)quinoline anion]. They include a dimeric molecule, [Fe(qcq)(CN)(3)][Mn(3-MeOsalen)(H(2)O)] x 2 H(2)O [2 x 2 H(2)O; 3-MeOsalen = N,N'-ethylenebis(3-methoxysalicylideneiminato) dianion], and three 1D zigzag chains, [Fe(qcq)(CN)(3)][Mn(5-Clsalen)] x 3 H(2)O [3 x 2 MeOH; 5-Clsalen = N,N'-ethylenebis(5-chlorosalicylideneiminato) dianion], [Fe(qcq)(CN)(3)][Mn(5-Brsalen)] x 2 MeOH [4 x 2 MeOH; 5-Brsalen = N,N'-ethylenebis(5-bromosalicylideneiminato) dianion], and Fe(qcq)(CN)(3)][Mn(salen)].MeCN x H(2)O [5 x MeCN; salen = N,N'-ethylenebis(salicylideneiminato) dianion]. The complexes consist of extensive hydrogen bonding and pi-pi stacking interactions, generating multidimensional structures. Magnetic studies demonstrate that antiferromagnetic couplings are operative between Fe(III) and Mn(III) centers bridged by cyanide ligands. On the basis of an infinite chain model, magnetic coupling parameters of 2-5 range from -9.3 to -14.1 cm(-1). A long-range order is observed at 2.3 K for 3 and 2.2 K for 4, while compound 5 shows spin glass behavior possibly coupled with magnetic ordering.

  17. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    PubMed

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw; Potempa, Jan; Riise, Erik

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18) by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15), shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48). Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  18. Structural Studies of Apo Nosl, an Accessory Protein of the Nitrous Oxide Reductase System: Insights from Structural Homology with MerB, a Mercury Resistance Protein

    SciTech Connect

    Taubner, Lara M.; McGuirl, Michele A.; Dooley, David M.; Copie, Valerie

    2006-09-19

    The formation of the unique catalytic tetranuclear copper cluster (CuZ) of nitrous oxide reductase, N2OR, requires the coexpression of a multiprotein assembly apparatus encoded by the nosDFYL operon. NosL, one of the proteins encoded by this transcript, is a 20 kDa lipoprotein of the periplasm that has been shown to bind copper(I), although its function has yet to be detemined. Cu(I) EXAFS data collected on the holo protein demonstrated that features of the copper binding site are consistent with a role for this protein as a metallochaperone, a class of metal ion transporters involved in metal resistance, homeostasis, and metallocluster biosynthesis. To test this hypothesis and to gain insight into other potential functional roles for this protein in the N2OR system, the three-dimensional solution structure of apo NosL has been solved by solution NMR methods. The structure of apo NosL consists of two relatively independent homologous domains that adopt an unusual topology.

  19. Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015.

    PubMed

    Al Hammadi, Zulaikha M; Chu, Daniel K W; Eltahir, Yassir M; Al Hosani, Farida; Al Mulla, Mariam; Tarnini, Wasim; Hall, Aron J; Perera, Ranawaka A P M; Abdelkhalek, Mohamed M; Peiris, J S M; Al Muhairi, Salama S; Poon, Leo L M

    2015-12-01

    In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.

  20. Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites.

    PubMed

    Munch, Henrik K; Nygaard, Jesper; Christensen, Niels Johan; Engelbrekt, Christian; Østergaard, Mads; Porsgaard, Trine; Hoeg-Jensen, Thomas; Zhang, Jingdong; Arleth, Lise; Thulstrup, Peter W; Jensen, Knud J

    2016-02-12

    Controlled self-assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal-ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2'-bipyridine (bipy) ligand to HI, yielding HI-bipy, enabled Zn(II)-binding hexamers to SA into trimers of hexamers, [[HI-bipy]6]3, driven by octahedral coordination to a Fe(II)  ion. The structures were studied in solution by small-angle X-ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe(II) than Zn(II)  ions, enabling control of the hexamer formation with Zn(II) and the formation of trimers of hexamers with Fe(II)  ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.

  1. Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015

    PubMed Central

    Al Hammadi, Zulaikha M.; Chu, Daniel K.W.; Eltahir, Yassir M.; Al Hosani, Farida; Al Mulla, Mariam; Tarnini, Wasim; Hall, Aron J.; Perera, Ranawaka A.P.M.; Abdelkhalek, Mohamed M.; Peiris, J.S.M.

    2015-01-01

    In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries. PMID:26584223

  2. [Treatment of fractures of the mandibular condyle. Experiences at the Department of Oral Medicine and Maxillofacial Surgery at Toulon-La-Seyne/Mer].

    PubMed

    Ribault, J Y; Lestage, F; Gacon, J; Vittel, P; Roubaudi, G; Pernice, L; Jeannenot, J; Laroche, D; Fourestier, J

    1997-11-01

    The fractures of the gnathic condyle are constantly increasing due to the violent impact on the chine. The functional treatment is essential for good results whereas the restitution of a functional joint, i.e. teeth that engage into one another, is satisfactory for the patient as it can also justify a possible surgical reduction in such cases when significant shifts of fragments resulting from the fractures are present.

  3. Traceurs sédimentaires des variations du niveau marin et de la mousson sud-est asiatique depuis 450 ka en mer de Chine du Sud

    NASA Astrophysics Data System (ADS)

    Boulay, Sébastien; Colin, Christophe; Trentesaux, Alain

    2008-06-01

    In order to reconstruct the past variations of the Southeast Asian monsoon intensity and estimate the sedimentary system reactivity to climatic changes in Southeast Asia over the last 450 kyr, mineralogical and sedimentological analyses have been performed on the terrigenous fraction of the South China Sea sediment. End-member modelling coupled with grain size data discriminates three end-members that determine the nature and intensity of the main sediment transport vectors. Low sea-level stands are characterized by sediment reworking that allows transportation of a coarse end-member (20-40 μm) to the deep-basin. By contrast, the other end-members (4-6 μm; 9-13 μm) are controlled by the shoreline position (sea level) and/or by changes of the rivers capacity transport (monsoon). Finally, aeolian input to the northern margin of the South China Sea can be considered negligible compared to the massive fluvial input and the reworking of the sediments.

  4. Strategy for the In Situ Search of Evaporite and Carbonate Deposits in Gusev Crater Within the 2003 MER A Landing Ellipse

    NASA Technical Reports Server (NTRS)

    Grin, E. A.; Cabrol, N. A.; Leone, G.; Orofino, V.

    2002-01-01

    Topographic profiles and MOC images suggest that the flat floor of Gusev results from sediment deposition in the absence of strong sublacustrine currents. This setting is favorable to preserve undisturbed sedimentary sequences and identify carbonates and evaporites in the landing ellipse. Additional information is contained in the original extended abstract.

  5. Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea.

    PubMed

    Lee, Hyukmin; Ki, Chang-Seok; Sung, Heungsup; Kim, Sinyoung; Seong, Moon-Woo; Yong, Dongeun; Kim, Jae-Seok; Lee, Mi-Kyung; Kim, Mi-Na; Choi, Jong-Rak; Kim, Jeong-Ho

    2016-03-01

    The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual. PMID:27104019

  6. Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea

    PubMed Central

    Sung, Heungsup; Kim, Sinyoung; Seong, Moon-Woo; Yong, Dongeun; Kim, Jae-Seok; Lee, Mi-Kyung; Choi, Jong-Rak; Kim, Jeong-Ho

    2016-01-01

    The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual. PMID:27104019

  7. Pointers from the Americas.

    PubMed

    Aragon-choudhury, P

    1992-01-01

    During a sharing session which took place at a conference sponsored by the Philippine Institute for Social Studies and Action in 1991, Peruvian Victoria Villanueva and US citizen Margaret Ann Schuller discussed their work. Schuller reported on her upcoming book entitled "Freedom from Violence: Women's Strategies Around the World." In addition to proposing a definition of violence against women, the book will include 12 case studies from Malaysia, Bolivia, Mexico, India, Pakistan, Thailand, Sri Lanka, Brazil, Zimbabwe, Chile, Africa, and Alaska describing how national organizations of women are dealing with the problem. An important advance is the development of a framework to look at the connection which exists between violence and health issues. Villanueva described the work of the Movimiento Manuela Ramos, which was organized informally to deal with reproductive rights and abortion and has since expanded to parent groups of women who defend legal and medical cases as paid paralegals. Manuela Ramos uses popular media, traditional drama, and even state television to publicize its issues. Manuela Ramos has accomplished important work on rape, unsafe abortion, and maternal mortality, but most importantly, the women involved with the organization have had the opportunity to develop their self-esteem. PMID:12288567

  8. Pointers from the Americas.

    PubMed

    Aragon-choudhury, P

    1992-01-01

    During a sharing session which took place at a conference sponsored by the Philippine Institute for Social Studies and Action in 1991, Peruvian Victoria Villanueva and US citizen Margaret Ann Schuller discussed their work. Schuller reported on her upcoming book entitled "Freedom from Violence: Women's Strategies Around the World." In addition to proposing a definition of violence against women, the book will include 12 case studies from Malaysia, Bolivia, Mexico, India, Pakistan, Thailand, Sri Lanka, Brazil, Zimbabwe, Chile, Africa, and Alaska describing how national organizations of women are dealing with the problem. An important advance is the development of a framework to look at the connection which exists between violence and health issues. Villanueva described the work of the Movimiento Manuela Ramos, which was organized informally to deal with reproductive rights and abortion and has since expanded to parent groups of women who defend legal and medical cases as paid paralegals. Manuela Ramos uses popular media, traditional drama, and even state television to publicize its issues. Manuela Ramos has accomplished important work on rape, unsafe abortion, and maternal mortality, but most importantly, the women involved with the organization have had the opportunity to develop their self-esteem.

  9. Understanding and Enhancing the Use of Multiple External Representations in Chemistry Education

    ERIC Educational Resources Information Center

    Corradi, David; Elen, Jan; Clarebout, Geraldine

    2012-01-01

    Theories on learning with Multiple External Representations (MER) claim that low prior knowledge learners in science have difficulties using MER, which are seen as necessary to achieve a conceptual understanding. In two experiments, we analyze the mechanisms underlying the learning of chemistry with MER. Our first experiment focuses on how MER can…

  10. Inhibition of proprotein convertases abrogates processing of the middle eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity.

    PubMed

    Gierer, Stefanie; Müller, Marcel A; Heurich, Adeline; Ritz, Daniel; Springstein, Benjamin L; Karsten, Christina B; Schendzielorz, Alexander; Gnirß, Kerstin; Drosten, Christian; Pöhlmann, Stefan

    2015-03-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S-transfected and MERS-CoV-infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S-dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.

  11. A new coordination tetra­mer of copper(I) iodide and benzyl­dimethyl­amine: tetra-μ3-iodido-tetra­kis[(benzyl­dimethyl­amine-κN)copper(I)

    PubMed Central

    Yang, Shuying; Li, Yuebao; Cui, Yujie; Pan, Jianguo

    2009-01-01

    The title compound, [Cu4I4(C9H13N)4], has a distorted cubane-like [Cu4I4] core structure. Each CuI atom is tetra­hedrally coordinated by three I atoms and one N atom of an benzyl­dimethyl­amine ligand. Each I atom acts as a μ3-ligand, linking three CuI atoms. The Cu—I bond distances vary between 2.6328 (7) and 2.7121 (6) Å, while the Cu—N bond distances vary between 2.107 (3) and 2.122 (3) Å. PMID:21583366

  12. The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

    PubMed

    Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

    2009-04-01

    Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

  13. On the origin of framboidal pyrite in sediments of the Suakin Deep (Red Sea)Sur l'origine de la pyrite framboïdale dans les sédiments de la fosse Suakin (mer Rouge)

    NASA Astrophysics Data System (ADS)

    Pierret, Marie-Claire; Blanc, Gérard; Clauer, Norbert

    2000-01-01

    Suakin Deep is one of the southern depressions of the Red Sea, with sediments containing up to 20 % of pyrite. Although metalliferous sediments result from hydrothermal activity in most deeps, those of Suakin have different characteristics. Pyrite is framboïdal and the REE patterns of its sediments are similar to those of biodetrital sediments. The sediments seem to be of biodetritic origin and to have undergone diagenetic changes without hydrothermal activity.

  14. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

    NASA Technical Reports Server (NTRS)

    Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.; Sarma, R. H.

    1997-01-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex between the anti HIV-1 gag ribozyme and its abortive DNA substrate manifests in the detection of a continuous track of A.T base pairs; this suggests that the interaction between the ribozyme and its DNA substrate is stronger than the one observed in the case of the free ribozyme where the bases in stem I and stem III regions interact strongly with the ribozyme core region (Sarma, R. H., et al. FEBS Letters 375, 317-23, 1995). The complex formation provides certain guidelines in the design of suitable therapeutic ribozymes. If the residues in the ribozyme stem regions interact with the conserved core, it may either prevent or interfere with the formation of a catalytically active tertiary structure.

  15. Les possibilités et limitations de l'atomisation électrothermique en spectrométrie d'absorption atomique lors de l'analyse directe des metaux lourds dans l'eau de mer

    NASA Astrophysics Data System (ADS)

    Hoenig, M.; Wollast, R.

    This work shows the analytical possibilities of an electrothermal atomizer for the direct determination of trace metals in sea-water. The high background signals generated by the matrix perturb in particular volatile elements because of the low decomposition temperature allowed. In the case of cadmium, addition of ascorbic acid to the sample permits the modification of the atomization mechanism and the reduction of the optimum temperature. Under these conditions, absorption peak of the cadmium precedes the background absorption and consequently the analysis is no longer limited by the magnitude of the matrix signal: the determination of cadmium concentrations far below the μg -1 level is easily possible. Although the direct determination of the other elements should be in principle less disturbed by the background, the analytical performance is poorer than for cadmium. Limits of determination of the order from 0.1 to 1 μg -1 can be reached for chromium, copper and manganese. Lead and nickel appeared to be the most difficult elements; their direct determination is only possible in polluted coastal or estuarine waters. The injection of the sample as an aerosol into hot graphite tube showed to be well adapted to this kind of investigations. The simultaneous visualization of specific and background signals allows interpretations which until now were impossible with commercially available apparatus.

  16. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments.

    PubMed

    Ojha, R P; Dhingra, M M; Sarma, M H; Myer, Y P; Setlik, R F; Shibata, M; Kazim, A L; Ornstein, R L; Rein, R; Turner, C J; Sarma, R H

    1997-10-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex between the anti HIV-1 gag ribozyme and its abortive DNA substrate manifests in the detection of a continuous track of A.T base pairs; this suggests that the interaction between the ribozyme and its DNA substrate is stronger than the one observed in the case of the free ribozyme where the bases in stem I and stem III regions interact strongly with the ribozyme core region (Sarma, R. H., et al. FEBS Letters 375, 317-23, 1995). The complex formation provides certain guidelines in the design of suitable therapeutic ribozymes. If the residues in the ribozyme stem regions interact with the conserved core, it may either prevent or interfere with the formation of a catalytically active tertiary structure. PMID:9399149

  17. Functions, Evolution, and Application of the Supramolecular Machines of Hg Detoxification

    SciTech Connect

    Miller, Susan M.

    2009-11-27

    The bacterial mercury resistance (mer) operon functions in Hg biogeochemistry and bioremediation by converting reactive inorganic [Hg(II)] and organic [RHg(I)] mercurials to relatively inert monoatomic mercury vapor, Hg(0). Its genes regulate expression (MerR, MerD, MerOP), import Hg(II) (MerT, MerP, and MerC), and demethylate (MerB) and reduce (MerA) mercurials. We focus on how these components interact with each other and with the host cell to allow cells to survive and detoxify Hg compounds. Understanding how this ubiquitous detoxification system fits into the biology and ecology of its bacterial host is essential to guide interventions that support and enhance Hg remediation. At a more basic level, studies of interactions between the metal ion trafficking proteins in this pathway provide insights into general mechanisms used by proteins in pathways involved in trafficking of other metal ions in cells of all types of organisms, including pathways for essential metal ions such as Cu and Zn and other toxic metal ions such as Cd. In this project we focused on investigations of proteins from mer operons found in gamma-proteobacteria with specific objectives to use biophysical and biochemical approaches to detect and define (1) interactions between the structural components of the key detoxifying mer operon enzyme, mercuric ion reductase (MerA), (2) interactions between the components of MerA and the other mer operon enzyme, organomercurial lyase (MerB), and (3) to investigate the structure and interactions of integral membrane transport proteins, MerT and MerC, with MerA.

  18. The Functions of Multiple Representations.

    ERIC Educational Resources Information Center

    Ainsworth, Shaaron

    1999-01-01

    Discusses multiple representations and multimedia learning environments; describes a functional taxonomy of MERs (multiple external representations); and considers how MERs are used to support cognitive processes in learning and problem solving with computers. (Contains 41 references.) (Author/LRW)

  19. Geochemical Anomalies and Rock Coatings on Mars: Significance to MSR

    NASA Astrophysics Data System (ADS)

    Clark, B. C.; Gellert, R.

    2016-08-01

    Mars rover missions [Spirit (MER-A), Opportunity (MER-B), Curiosity (MSL)] have discovered unexpected geochemical extremes from aqueous alteration. Coatings and certain trace elements show large enrichment's well beyond magmatic differentiation.

  20. Teaching Medical Informatics Skills During a Clinical Clerkship

    PubMed Central

    Codish, Shlomi; Leibowitz, Akiva; Weinreb, Baruch

    2005-01-01

    Medical students use many forms of medical electronic resources (MER) during clinical clerkships. Such resources may be inaccurate, irrelevant or inappropriate, yet most medical students do not receive guidance on the use of MER. During the earliest clinical clerkship we gave a series of seminars and assignments on the use of MER. These were well accepted and were followed by increased knowledge in the use of MER. PMID:16779216

  1. Mercury Reduction and Methyl Mercury Degradation by the Soil Bacterium Xanthobacter autotrophicus Py2

    PubMed Central

    Petrus, Amanda K.; Rutner, Colin; Liu, Songnian; Wang, Yingjiao

    2015-01-01

    Two previously uncharacterized potential broad-spectrum mercury (Hg) resistance operons (mer) are present on the chromosome of the soil Alphaproteobacteria Xanthobacter autotrophicus Py2. These operons, mer1 and mer2, contain two features which are commonly found in mer operons in the genomes of soil and marine Alphaproteobacteria, but are not present in previously characterized mer operons: a gene for the mercuric reductase (MerA) that encodes an alkylmercury lyase domain typical of those found on the MerB protein, and the presence of an additional gene, which we are calling merK, with homology to glutathione reductase. Here, we demonstrate that Py2 is resistant to 0.2 μM inorganic mercury [Hg(II)] and 0.05 μM methylmercury (MeHg). Py2 is capable of converting MeHg and Hg(II) to elemental mercury [Hg(0)], and reduction of Hg(II) is induced by incubation in sub toxic concentrations of Hg(II). Transcription of the merA genes increased with Hg(II) treatment, and in both operons merK resides on the same polycistronic mRNA as merA. We propose the use of Py2 as a model system for studying the contribution of mer to Hg mobility in soil and marine ecosystems. PMID:26341208

  2. Final Report - Molecular Mechanisms of Bacterial Mercury Transformation - UCSF

    SciTech Connect

    Miller, Susan M.

    2014-04-24

    The bacterial mercury resistance (mer) operon functions in Hg biogeochemistry and bioremediation by converting reactive inorganic Hg(II) and organic [RHg(II)]1+ mercurials to relatively inert monoatomic mercury vapor, Hg(0). Its genes regulate operon expression (MerR, MerD, MerOP), import Hg(II) (MerT, MerP, and MerC), and demethylate (MerB) and reduce (MerA) mercurials. We focus on how these components interact with each other and with the host cell to allow cells to survive and detoxify Hg compounds. Understanding how this ubiquitous detoxification system fits into the biology and ecology of its bacterial host is essential to guide interventions that support and enhance Hg remediation. In the current overall project we focused on two aspects of this system: (1) investigations of the energetics of Hg(II)-ligand binding interactions, and (2) both experimental and computational approaches to investigating the molecular mechanisms of Hg(II) acquisition by MerA and intramolecular transfer of Hg(II) prior to reduction within the MerA enzyme active site. Computational work was led by Prof. Jeremy Smith and took place at the University of Tennessee, while experimental work on MerA was led by Prof. Susan Miller and took place at the University of California San Francisco.

  3. Identification of Information Types and Sources by the Public for Promoting Awareness of Middle East Respiratory Syndrome Coronavirus in Saudi Arabia

    ERIC Educational Resources Information Center

    Hoda, Jradi

    2016-01-01

    Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of serious consequences caused by MERS Coronavirus (MERS-CoV). Saudi communities still lack awareness of available protective measures to prevent the transmission of the virus. It is necessary to explore the current information-seeking strategies and preferences for…

  4. Structural Biology of The sequestration & Transport of Heavy Metal Toxins: NMR Structure Determination of Proteins Containing the CYS-X-Y-Metal Binding Motif

    SciTech Connect

    Stanley J. Opella

    2004-03-10

    The support from the Department of Energy enabled us to initiate research on several proteins from the bacterial mercury detoxification system; in particular, we were able to determine the structures of MerP and related metal binding sequences. We have also worked on the membrane transport proteins MerF and MerT.

  5. CENP-B box and pJalpha sequence distribution in human alpha satellite higher-order repeats (HOR).

    PubMed

    Rosandić, Marija; Paar, Vladimir; Basar, Ivan; Gluncić, Matko; Pavin, Nenad; Pilas, Ivan

    2006-01-01

    Using our Key String Algorithm (KSA) to analyze Build 35.1 assembly we determined consensus alpha satellite higher-order repeats (HOR) and consensus distributions of CENP-B box and pJalpha motif in human chromosomes 1, 4, 5, 7, 8, 10, 11, 17, 19, and X. We determined new suprachromosomal family (SF) assignments: SF5 for 13mer (2211 bp), SF5 for 13mer (2214 bp), SF2 for 11mer (1869 bp), SF1 for 18mer (3058 bp), SF3 for 12mer (2047 bp), SF3 for 14mer (2379 bp), and SF5 for 17mer (2896 bp) in chromosomes 4, 5, 8, 10, 11, 17, and 19, respectively. In chromosome 5 we identified SF5 13mer without any CENP-B box and pJalpha motif, highly homologous (96%) to 13mer in chromosome 19. Additionally, in chromosome 19 we identified new SF5 17mer with one CENP-B box and pJalpha motif, aligned to 13mer by deleting four monomers. In chromosome 11 we identified SF3 12mer, homologous to 12mer in chromosome X. In chromosome 10 we identified new SF1 18mer with eight CENP-B boxes in every other monomer (except one). In chromosome 4 we identified new SF5 13mer with CENP-B box in three consecutive monomers. We found four exceptions to the rule that CENP-B box belongs to type B and pJalpha motif to type A monomers. PMID:17115329

  6. Serological Study of An Imported Case of Middle East Respiratory Syndrome and His Close Contacts in China, 2015.

    PubMed

    Wang, Wen Ling; Wang, Hui Juan; Deng, Yao; Song, Tie; Lan, Jia Ming; Wu, Gui Zhen; Ke, Chang Wen; Tan, Wen Jie

    2016-03-01

    The first imported Middle East respiratory syndrome (MERS) case in China was identified in May 2015. We determined the kinetics of antibody (IgG and IgM) and neutralizing antibodies against MERS-coronavirus (MERS-CoV) in this case before discharge. Moreover, no seroconversion was found among 53 close contacts by anti-MERS IgG antibody enzyme-linked immunosorbent assay (ELISA) of paired serum samples. These findings suggest that neither community nor nosocomial transmission of MERS-CoV occurred in China. PMID:27109133

  7. Professional tennis players' serve: correlation between segmental angular momentums and ball velocity.

    PubMed

    Martin, Caroline; Kulpa, Richard; Delamarche, Paul; Bideau, Benoit

    2013-03-01

    The purpose of the study was to identify the relationships between segmental angular momentum and ball velocity between the following events: ball toss, maximal elbow flexion (MEF), racket lowest point (RLP), maximal shoulder external rotation (MER), and ball impact (BI). Ten tennis players performed serves recorded with a real-time motion capture. Mean angular momentums of the trunk, upper arm, forearm, and the hand-racket were calculated. The anteroposterior axis angular momentum of the trunk was significantly related with ball velocity during the MEF-RLP, RLP-MER, and MER-BI phases. The strongest relationships between the transverse-axis angular momentums and ball velocity followed a proximal-to-distal timing sequence that allows the transfer of angular momentum from the trunk (MEF-RLP and RLP-MER phases) to the upper arm (RLP-MER phase), forearm (RLP-MER and MER-BI phases), and the hand-racket (MER-BI phase). Since sequence is crucial for ball velocity, players should increase angular momentums of the trunk during MEF-MER, upper arm during RLP-MER, forearm during RLP-BI, and the hand-racket during MER-BI.

  8. Using max entropy ratio of recurrence plot to measure electrocorticogram changes in epilepsy patients

    NASA Astrophysics Data System (ADS)

    Yan, Jiaqing; Wang, Yinghua; Ouyang, Gaoxiang; Yu, Tao; Li, Xiaoli

    2016-02-01

    A maximum entropy ratio (MER) method is firstly adapted to investigate the high-dimensional Electrocorticogram (ECoG) data from epilepsy patients. MER is a symbolic analysis approach for the detection of recurrence domains of complex dynamical systems from time series. Data were chosen from eight patients undergoing pre-surgical evaluation for drug-resistant temporal lobe epilepsy. MERs for interictal and ictal data were calculated and compared. A statistical test was performed to evaluate the ability of MER to separate the interictal state from the ictal state. MER showed significant changes from the interictal state into the ictal state, where MER was low at the ictal state and is significantly different with that at the interictal state. These suggest that MER is able to separate the ictal state from the interictal state based on ECoG data. It has the potential of detecting the transition between normal brain activity and the ictal state.

  9. Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections.

    PubMed

    Zumla, Alimuddin; Azhar, Esam I; Arabi, Yaseen; Alotaibi, Badriah; Rao, Martin; McCloskey, Brian; Petersen, Eskild; Maeurer, Markus

    2015-11-01

    Three years after its first discovery in Jeddah Saudi Arabia, the novel zoonotic pathogen of humans, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a major threat to global health security.(1) Sporadic community acquired cases of MERS continue to be reported from the Middle East. The recent nosocomial outbreaks in hospitals in Seoul, Korea and at the National Guard Hospital in Riyadh, Saudi Arabia indicate the epidemic potential of MERS-CoV. Currently there are no effective anti-MERS-CoV anti-viral agents or therapeutics and MERS is associated with a high mortality rate (40%) in hospitalised patients. A large proportion of MERS patients who die have a range of pulmonary pathology ranging from pneumonia to adult respiratory distress syndrome with multi-organ failure, compounded by co-morbidities, reflecting a precarious balance of interactions between the host-immune system and MERS-CoV. Whilst we wait for new MERS-CoV specific drugs, therapeutics and vaccines to be developed, there is a need to advance a range of Host-Directed Therapies. A range of HDTs are available, including commonly used drugs with good safety profiles, which could augment host innate and adaptive immune mechanisms to MERS-CoV, modulate excessive inflammation and reduce lung tissue destruction. We discuss the rationale and potential of using Host-Directed Therapies for improving the poor treatment outcomes associated with MERS. Carefully designed randomized controlled trials will be needed to determine whether HDTs could benefit patients with MERS. The recurrent outbreaks of MERS-CoV infections at hospitals in the Middle East present unique opportunities to conduct randomized clinical trials. The time has come for a more coordinated global response to MERS and a multidisciplinary global MERS-CoV response group is required to take forward priority research agendas. PMID:26365771

  10. High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea.

    PubMed

    Shin, Soo-Yong; Seo, Dong-Woo; An, Jisun; Kwak, Haewoon; Kim, Sung-Han; Gwack, Jin; Jo, Min-Woo

    2016-09-06

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: "MERS", " ("MERS (in Korean)"), " ("MERS symptoms (in Korean)"), and " ("MERS hospital (in Korean)"). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.

  11. Assessment of the risk posed to Singapore by the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea

    PubMed Central

    Zhang, Emma Xuxiao; Oh, Olivia Seen Huey; See, Wanhan; Raj, Pream; James, Lyn; Khan, Kamran

    2016-01-01

    Objective To assess the public health risk to Singapore posed by the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea in 2015. Methods The likelihood of importation of MERS cases and the magnitude of the public health impact in Singapore were assessed to determine overall risk. Literature on the epidemiology and contextual factors associated with MERS coronavirus infection was collected and reviewed. Connectivity between the Republic of Korea and Singapore was analysed. Public health measures implemented by the two countries were reviewed. Results The epidemiology of the 2015 MERS outbreak in the Republic of Korea remained similar to the MERS outbreaks in Saudi Arabia. In addition, strong infection control and response measures were effective in controlling the outbreak. In view of the air traffic between Singapore and MERS-affected areas, importation of MERS cases into Singapore is possible. Nonetheless, the risk of a serious public health impact to Singapore in the event of an imported case of MERS would be mitigated by its strong health-care system and established infection control practices. Discussion The MERS outbreak was sparked by an exported case from the Middle East, which remains a concern as the reservoir of infection (thought to be camels) continues to exist in the Middle East, and sporadic cases in the community and outbreaks in health-care settings continue to occur there. This risk assessment highlights the need for Singapore to stay vigilant and to continue enhancing core public health capacities to detect and respond to MERS coronavirus. PMID:27508087

  12. High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea.

    PubMed

    Shin, Soo-Yong; Seo, Dong-Woo; An, Jisun; Kwak, Haewoon; Kim, Sung-Han; Gwack, Jin; Jo, Min-Woo

    2016-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: "MERS", " ("MERS (in Korean)"), " ("MERS symptoms (in Korean)"), and " ("MERS hospital (in Korean)"). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS. PMID:27595921

  13. The Mercury Resistance Operon: From an Origin in a Geothermal Environment to an Efficient Detoxification Machine

    PubMed Central

    Boyd, Eric S.; Barkay, Tamar

    2012-01-01

    Mercuric mercury (Hg[II]) is a highly toxic and mobile element that is likely to have had a pronounced and adverse effect on biology since Earth’s oxygenation ∼2.4 billion years ago due to its high affinity for protein sulfhydryl groups, which upon binding destabilize protein structure and decrease enzyme activity, resulting in a decreased organismal fitness. The central enzyme in the microbial mercury detoxification system is the mercuric reductase (MerA) protein, which catalyzes the reduction of Hg(II) to volatile Hg(0). In addition to MerA, mer operons encode for proteins involved in regulation, Hg binding, and organomercury degradation. Mer-mediated approaches have had broad applications in the bioremediation of mercury-contaminated environments and industrial waste streams. Here, we examine the composition of 272 individual mer operons and quantitatively map the distribution of mer-encoded functions on both taxonomic SSU rRNA gene and MerA phylogenies. The results indicate an origin and early evolution of MerA among thermophilic bacteria and an overall increase in the complexity of mer operons through evolutionary time, suggesting continual gene recruitment and evolution leading to an improved efficiency and functional potential of the Mer detoxification system. Consistent with a positive relationship between the evolutionary history and topology of MerA and SSU rRNA gene phylogenies (Mantel R = 0.81, p < 0.01), the distribution of the majority of mer functions, when mapped on these phylograms, indicates an overall tendency to inherit mer-encoded functions through vertical descent. However, individual mer functions display evidence of a variable degree of vertical inheritance, with several genes exhibiting strong evidence for acquisition via lateral gene transfer and/or gene loss. Collectively, these data suggest that (i) mer has evolved from a simple system in geothermal environments to a widely distributed and more complex and efficient

  14. Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection

    PubMed Central

    Hajeer, Ali H.; Balkhy, Hanan; Johani, Sameera; Yousef, Mohammed Z.; Arabi, Yaseen

    2016-01-01

    BACKGROUND: Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia. AIM: We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit. METHODS: A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls. RESULTS: Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome. CONCLUSIONS: Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS. PMID:27512511

  15. Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Payne, Daniel C.; Iblan, Ibrahim; Alqasrawi, Sultan; Al Nsour, Mohannad; Rha, Brian; Tohme, Rania A.; Abedi, Glen R.; Farag, Noha H.; Haddadin, Aktham; Sanhouri, Tarek Al; Jarour, Najwa; Swerdlow, David L.; Jamieson, Denise J.; Pallansch, Mark A.; Haynes, Lia M.; Gerber, Susan I.; Al Abdallat, Mohammad Mousa

    2015-01-01

    We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing. PMID:24474813

  16. Stillbirth during infection with Middle East respiratory syndrome coronavirus.

    PubMed

    Payne, Daniel C; Iblan, Ibrahim; Alqasrawi, Sultan; Al Nsour, Mohannad; Rha, Brian; Tohme, Rania A; Abedi, Glen R; Farag, Noha H; Haddadin, Aktham; Al Sanhouri, Tarek; Jarour, Najwa; Swerdlow, David L; Jamieson, Denise J; Pallansch, Mark A; Haynes, Lia M; Gerber, Susan I; Al Abdallat, Mohammad Mousa

    2014-06-15

    We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing. PMID:24474813

  17. Middle East respiratory syndrome coronavirus: epidemiology and disease control measures

    PubMed Central

    Al-Tawfiq, Jaffar A; Memish, Ziad A

    2014-01-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection. PMID:25395865

  18. Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014

    PubMed Central

    Hastings, Deborah L.; Tokars, Jerome I.; Abdel Aziz, Inas Zakaria A.M.; Alkhaldi, Khulud Z.; Bensadek, Areej T.; Alraddadi, Basem M.; Jokhdar, Hani; Jernigan, John A.; Garout, Mohammed A.; Tomczyk, Sara M.; Oboho, Ikwo K.; Geller, Andrew I.; Arinaminpathy, Nimalan; Swerdlow, David L.

    2016-01-01

    During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks. PMID:27089550

  19. Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi

    PubMed Central

    Nguyen, Duc; Aden, Bashir; Al Bandar, Zyad; Al Dhaheri, Wafa; Abu Elkheir, Kheir; Khudair, Ahmed; Al Mulla, Mariam; El Saleh, Feda; Imambaccus, Hala; Al Kaabi, Nawal; Sheikh, Farrukh Amin; Sasse, Jurgen; Turner, Andrew; Abdel Wareth, Laila; Weber, Stefan; Al Ameri, Asma; Abu Amer, Wesal; Alami, Negar N.; Bunga, Sudhir; Haynes, Lia M.; Hall, Aron J.; Kallen, Alexander J.; Kuhar, David; Pham, Huong; Pringle, Kimberly; Tong, Suxiang; Whitaker, Brett L.; Gerber, Susan I.; Al Hosani, Farida Ismail

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013–May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities. PMID:26981708

  20. Middle East respiratory syndrome: obstacles and prospects for vaccine development

    PubMed Central

    Papaneri, Amy B.; Johnson, Reed F.; Wada, Jiro; Bollinger, Laura; Jahrling, Peter B.; Kuhn, Jens H.

    2016-01-01

    Summary The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates in vivo testing of candidate vaccines. Second, due to the low number of MERS cases, pharmaceutical companies have little incentive to pursue MERS vaccine production as the costs of clinical trials are high. In addition, the timeline from bench research to approved vaccine use is 10 years or longer. Using novel methods and cost-saving strategies, genetically engineered vaccines can be produced quickly and cost-effectively. Along with progress in MERS animal model development, these obstacles can be circumvented or at least mitigated. PMID:25864502

  1. Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment Epithelium-derived Factor*

    PubMed Central

    Kenealey, Jason; Subramanian, Preeti; Comitato, Antonella; Bullock, Jeanee; Keehan, Laura; Polato, Federica; Hoover, David; Marigo, Valeria; Becerra, S. Patricia

    2015-01-01

    The cytoprotective effects of pigment epithelium-derived factor (PEDF) require interactions between an as of a yet undefined region with a distinct ectodomain on the PEDF receptor (PEDF-R). Here we characterized the area in PEDF that interacts with PEDF-R to promote photoreceptor survival. Molecular docking studies suggested that the ligand binding site of PEDF-R interacts with the neurotrophic region of PEDF (44-mer, positions 78–121). Binding assays demonstrated that PEDF-R bound the 44-mer peptide. Moreover, peptide P1 from the PEDF-R ectodomain had affinity for the 44-mer and a shorter fragment within it, 17-mer (positions 98–114). Single residue substitutions to alanine along the 17-mer sequence were designed and tested for binding and biological activity. Altered 17-mer[R99A] did not bind to the P1 peptide, whereas 17-mer[H105A] had higher affinity than the unmodified 17-mer. Peptides 17-mer, 17-mer[H105A], and 44-mer exhibited cytoprotective effects in cultured retina R28 cells. Intravitreal injections of these peptides and PEDF in the rd1 mouse model of retinal degeneration decreased the numbers of dying photoreceptors, 17-mer[H105A] being most effective. The blocking peptide P1 hindered their protective effects both in retina cells and in vivo. Thus, in addition to demonstrating that the region composed of positions 98–114 of PEDF contains critical residues for PEDF-R interaction that mediates survival effects, the findings reveal distinct small PEDF fragments with neurotrophic effects on photoreceptors. PMID:26304116

  2. Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels.

    PubMed

    Widagdo, W; Raj, V Stalin; Schipper, Debby; Kolijn, Kimberley; van Leenders, Geert J L H; Bosch, Berend J; Bensaid, Albert; Segalés, Joaquim; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koopmans, Marion P; van den Brand, Judith M A; Haagmans, Bart L

    2016-05-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor--dipeptidyl peptidase 4 (DPP4)--is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission.

  3. Genomics and zoonotic infections: Middle East respiratory syndrome.

    PubMed

    Wernery, U; Lau, S K P; Woo, P C Y

    2016-04-01

    The emergence of Middle East respiratory syndrome (MERS) and the discovery of MERS coronavirus (MERS-CoV) in 2012 suggests that another SARS-like epidemic is occurring. Unlike the severe acute respiratory syndrome (SARS) epidemic, which rapidly disappeared in less than one year, MERS has persisted for over three years. More than 1,600 cases of MERS have been reported worldwide, and the disease carries a worryingly high fatality rate of >30%. A total of 182 MERS-CoV genomes have been sequenced, including 94 from humans and 88 from dromedary camels. The 182 genomes all share >99% identity, indicating minimal variation among MERS-CoV genomes. MERS-CoV is a lineage C Betacoronavirus (ßCoV). MERS-CoV genomes can be roughly divided into two clades: clade A, which contains only a few strains, and clade B, to which most strains belong. In contrast to ORF1ab and structural proteins, the putative proteins encoded by ORF3, ORF4a, ORF4b, ORF5 and ORF8b in the MERS-CoV genome do not share homology with any known host or virus protein, other than those of its closely related lineage C ßCoVs. Human and dromedary viral genomes have intermingled, indicating that multiple camel-to-human transmission events have occurred. The multiple origins of MERS-CoV suggest that the virus has been resident in dromedaries for many years. This is consistent with the detection of anti-MERS-CoV antibodies in dromedary camels as early as the 1980s. PMID:27217178

  4. Genomics and zoonotic infections: Middle East respiratory syndrome.

    PubMed

    Wernery, U; Lau, S K P; Woo, P C Y

    2016-04-01

    The emergence of Middle East respiratory syndrome (MERS) and the discovery of MERS coronavirus (MERS-CoV) in 2012 suggests that another SARS-like epidemic is occurring. Unlike the severe acute respiratory syndrome (SARS) epidemic, which rapidly disappeared in less than one year, MERS has persisted for over three years. More than 1,600 cases of MERS have been reported worldwide, and the disease carries a worryingly high fatality rate of >30%. A total of 182 MERS-CoV genomes have been sequenced, including 94 from humans and 88 from dromedary camels. The 182 genomes all share >99% identity, indicating minimal variation among MERS-CoV genomes. MERS-CoV is a lineage C Betacoronavirus (ßCoV). MERS-CoV genomes can be roughly divided into two clades: clade A, which contains only a few strains, and clade B, to which most strains belong. In contrast to ORF1ab and structural proteins, the putative proteins encoded by ORF3, ORF4a, ORF4b, ORF5 and ORF8b in the MERS-CoV genome do not share homology with any known host or virus protein, other than those of its closely related lineage C ßCoVs. Human and dromedary viral genomes have intermingled, indicating that multiple camel-to-human transmission events have occurred. The multiple origins of MERS-CoV suggest that the virus has been resident in dromedaries for many years. This is consistent with the detection of anti-MERS-CoV antibodies in dromedary camels as early as the 1980s.

  5. Development of FIAT-based Thermal Protection System Mass Estimating Relationships for NASA's Multi-Mission Earth Entry Concep

    NASA Technical Reports Server (NTRS)

    Sepka, Steven Andrew; Zarchi, Kerry Agnes; Maddock, Robert W.; Samareh, Jamshid A.

    2011-01-01

    Mass Estimating Relationships (MERs) have been developed for use in the Program to Optimize Simulated Trajectories II (POST2) as part of NASA's multi-mission Earth Entry Vehicle (MMEEV) concept. MERs have been developed for the thermal protection systems of PICA and of Carbon Phenolic atop Advanced Carbon-Carbon on the forebody and for SIRCA and Acusil II on the backshell. How these MERs were developed, the resulting equations, model limitations, and model accuracy are discussed herein.

  6. Development Of FIAT-Based Thermal Protection System Mass Estimating Relationships For NASA's Multi-Mission Earth Entry Concept

    NASA Technical Reports Server (NTRS)

    Sepka, Steven; Trumble, Kerry A.; Maddock, Robert W.; Samareh, Jamshid

    2012-01-01

    Mass Estimating Relationships (MERs) have been developed for use in the Program to Optimize Simulated Trajectories II (POST2) as part of NASA's multi-mission Earth Entry Vehicle (MMEEV) concept. MERs have been developed for the thermal protection systems of PICA and of Carbon Phenolic atop Advanced Carbon-Carbon on the forebody and for SIRCA and Acusil II on the backshell. How these MERs were developed, the resulting equations, model limitations, and model accuracy are discussed herein.

  7. Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013.

    PubMed

    Malik, Asim; El Masry, Karim Medhat; Ravi, Mini; Sayed, Falak

    2016-03-01

    As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin-peginterferon-α therapy.

  8. Laboratory Testing for Middle East Respiratory Syndrome Coronavirus, California, USA, 2013–2014

    PubMed Central

    Shahkarami, Mahtab; Yen, Cynthia; Glaser, Carol; Xia, Dongxiang; Watt, James

    2015-01-01

    Since Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged, the California Department of Public Health has coordinated efforts to identify possible cases in travelers to California, USA, from affected areas. During 2013–2014, the department investigated 54 travelers for MERS-CoV; none tested positive, but 32 (62%) of 52 travelers with suspected MERS-CoV had other respiratory viruses. PMID:26291839

  9. Mercury Resistance and Mercuric Reductase Activities and Expression among Chemotrophic Thermophilic Aquificae

    PubMed Central

    Freedman, Zachary; Zhu, Chengsheng

    2012-01-01

    Mercury (Hg) resistance (mer) by the reduction of mercuric to elemental Hg is broadly distributed among the Bacteria and Archaea and plays an important role in Hg detoxification and biogeochemical cycling. MerA is the protein subunit of the homodimeric mercuric reductase (MR) enzyme, the central function of the mer system. MerA sequences in the phylum Aquificae form the deepest-branching lineage in Bayesian phylogenetic reconstructions of all known MerA homologs. We therefore hypothesized that the merA homologs in two thermophilic Aquificae, Hydrogenobaculum sp. strain Y04AAS1 (AAS1) and Hydrogenivirga sp. strain 128-5-R1-1 (R1-1), specified Hg resistance. Results supported this hypothesis, because strains AAS1 and R1-1 (i) were resistant to >10 μM Hg(II), (ii) transformed Hg(II) to Hg(0) during cellular growth, and (iii) possessed Hg-dependent NAD(P)H oxidation activities in crude cell extracts that were optimal at temperatures corresponding with the strains' optimal growth temperatures, 55°C for AAS1 and 70°C for R1-1. While these characteristics all conformed with the mer system paradigm, expression of the Aquificae mer operons was not induced by exposure to Hg(II) as indicated by unity ratios of merA transcripts, normalized to gyrA transcripts for hydrogen-grown AAS1 cultures, and by similar MR specific activities in thiosulfate-grown cultures with and without Hg(II). The Hg(II)-independent expression of mer in the deepest-branching lineage of MerA from bacteria whose natural habitats are Hg-rich geothermal environments suggests that regulated expression of mer was a later innovation likely in environments where microorganisms were intermittently exposed to toxic concentrations of Hg. PMID:22773655

  10. Correlation Between UpToDate Searches and Reported Cases of Middle East Respiratory Syndrome During Outbreaks in Saudi Arabia.

    PubMed

    Thorner, Anna R; Cao, Bin; Jiang, Terrence; Warner, Amy J; Bonis, Peter A

    2016-01-01

    Background.  UpToDate is an online clinical decision support resource that is used extensively by clinicians around the world. Digital surveillance techniques have shown promise to aid with the detection and monitoring of infectious disease outbreaks. We sought to determine whether UpToDate searches for Middle East respiratory syndrome (MERS) could be used to detect and monitor MERS outbreaks in Saudi Arabia. Methods.  We analyzed daily searches related to MERS in Jeddah and Riyadh, Saudi Arabia during 3 outbreaks in these cities in 2014 and 2015 and compared them with reported cases during the same periods. We also compared UpToDate MERS searches in the affected cities to those in a composite of 4 negative control cities for the 2 outbreaks in 2014. Results.  UpToDate MERS searches during all 3 MERS outbreaks in Saudi Arabia showed a correlation to reported cases. In addition, UpToDate MERS search volume in Jeddah and Riyadh during the outbreak periods in 2014 was significantly higher than the concurrent search volume in the 4 negative control cities. In contrast, during the baseline periods, there was no difference between UpToDate searches for MERS in the affected cities compared with the negative control cities. Conclusions.  UpToDate search activity seems to be useful for detecting and monitoring outbreaks of MERS in Saudi Arabia.

  11. Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.

    PubMed Central

    Wainberg, M. A.; Deutsch, V.; Weiss, D. W.

    1976-01-01

    The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis. PMID:187207

  12. Instructional Developer as Content Specialist: Three Case Studies Utilizing the Instructional Development-Operations Research Model.

    ERIC Educational Resources Information Center

    Faust, Stephen M.

    1980-01-01

    Presents a 3-phase model (content research, specification, delivery) for instructional development-operations research and describes its application in developing courses in zoology, geology, and paleontology. (MER)

  13. KSC-03PD-1481

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - The overhead crane settles the Mars Exploration Rover 2 (MER-2) entry vehicle onto a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  14. KSC-03PD-1476

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - An overhead crane lifts the Mars Exploration Rover 2 (MER-2) entry vehicle from its stand to move it to a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  15. KSC-03PD-1479

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - Workers in the Payload Hazardous Servicing Facility help guide the Mars Exploration Rover 2 (MER- 2) entry vehicle toward a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  16. KSC-03PD-1425

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - The fairing for the Mars Exploration Rover 2 (MER-2/MER-A) arrives at Launch Complex 17-A, Cape Canaveral Air Force Station. It will be installed around the payload for protection during launch. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch date for MER-A is scheduled for June 5.

  17. KSC-03PD-1475

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - An overhead crane is in place to lift the Mars Exploration Rover 2 (MER-2) entry vehicle to move it to a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  18. KSC-03PD-1478

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - An overhead crane moves the Mars Exploration Rover 2 (MER-2) entry vehicle across the Payload Hazardous Servicing Facility toward a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  19. KSC-03PD-1477

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - An overhead crane moves the Mars Exploration Rover 2 (MER-2) entry vehicle across the Payload Hazardous Servicing Facility toward a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.

  20. KSC-03PD-1480

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. - With help from workers, the overhead crane lowers the Mars Exploration Rover 2 (MER-2) entry vehicle onto a spin table for a dry-spin test. The MER Mission consists of two identical rovers designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. Identical to each other, the rovers will land at different regions of Mars. Launch for MER-2 (MER-A) is scheduled for June 5.