Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System.

International audienceHuman coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G758 to RRSR↓R758), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies

Chemical characteristics of air from differing source regions during the Pacific Exploratory Mission‐Tropics A (PEM‐Tropics A)

Ten‐day backward trajectories are used to determine the origins of air parcels arriving at airborne DC‐8 chemical measurement sites during NASA\u27s Pacific Exploratory Mission‐Tropics A (PEM‐T) that was conducted during August‐October 1996. Those sites at which the air had a common geographical origin and transport history are grouped together, and statistical measures of chemical characteristics are computed. Temporal changes in potential temperature are used to determine whether trajectories experience a significant convective influence during the 10‐day period. Those trajectories that do not experience a significant convective influence are divided into four geographical categories depending on their origins and paths. Air parcels originating over Africa and South America are characterized by enhanced mixing ratios of O3, CO, HNO3, and PAN. The backward trajectories travel at high altitudes (∼10–11 km), covering long distances due to strong upper‐tropospheric westerly winds. The observed enhancement of combustion‐related species is attributed to biomass burning from distant sources to the west, extending even to South America. The relatively large value of Be‐7 probably is due either to less efficient removal of aerosols from upper tropospheric air or to small stratospheric contributions. Aged marine parcels are found to have relatively small concentrations of burning‐related species. Although these trajectories arrive at a wide range of aircraft altitudes, they do not pass over a land mass during the preceding 10‐day period. Air passing over Australia but no other land mass exhibits a combustion signature; however, photochemical product species such as O3 and PAN are less enhanced than in the long‐range transport category. These trajectories travel shorter distances and are at lower altitudes (∼5–8 km) than those reaching Africa and/or South America. The combustion influence on these parcels is attributed to biomass burning emissions injected over Australia. That burning is less widespread than in Africa and South America. Finally, trajectories originating over Southeast Asia appear to receive a weak combustion influence. However, compared to Africa and South America, Southeast Asia has a relatively small incidence of biomass burning. There is little combustion input from Australia due to the high transport altitudes compared to the lower heights of the convection. The Southeast Asian parcels exhibit the greatest NOx to ∑NOi ratio of any category, perhaps due to lightning. Parcels experiencing a significant convective influence also are examined. Most of these parcels pass through widespread, persistent convection along either the South Pacific Convergence Zone or Intertropical Convergence Zone approximately 5 days prior to arriving at the aircraft locations. Thus the category mostly represents marine convection. Mixing ratios of peroxides and acids in the convective category are found to be smaller than in parcels not experiencing convection. Small mixing ratios of Be‐7 and Pb‐210 suggest particle removal by precipitation

Improving regional ozone modeling through systematic evaluation of errors using the aircraft observations during the International Consortium for Atmospheric Research on Transport and Transformation

During the operational phase of the ICARTT field experiment in 2004, the regional air quality model STEM showed a strong positive surface bias and a negative upper troposphere bias (compared to observed DC-8 and WP-3 observations) with respect to ozone. After updating emissions from NEI 1999 to NEI 2001 (with a 2004 large point sources inventory update), and modifying boundary conditions, low-level model bias decreases from 11.21 to 1.45 ppbv for the NASA DC-8 observations and from 8.26 to −0.34 for the NOAA WP-3. Improvements in boundary conditions provided by global models decrease the upper troposphere negative ozone bias, while accounting for biomass burning emissions improved model performance for CO. The covariances of ozone bias were highly correlated to NOz, NOy, and HNO3 biases. Interpolation of bias information through kriging showed that decreasing emissions in SE United States would reduce regional ozone model bias and improve model correlation coefficients. The spatial distribution of forecast errors was analyzed using kriging, which identified distinct features, which when compared to errors in postanalysis simulations, helped document improvements. Changes in dry deposition to crops were shown to reduce substantially high bias in the forecasts in the Midwest, while updated emissions were shown to account for decreases in bias in the eastern United States. Observed and modeled ozone production efficiencies for the DC-8 were calculated and shown to be very similar (7.8) suggesting that recurring ozone bias is due to overestimation of NOx emissions. Sensitivity studies showed that ozone formation in the United States is most sensitive to NOx emissions, followed by VOCs and CO. PAN as a reservoir of NOx can contribute to a significant amount of surface ozone through thermal decomposition

Sources of upper tropospheric HO\u3csub\u3e\u3cem\u3ex\u3c/em\u3e\u3c/sub\u3e over the South Pacific Convergence Zone: A case study

A zero‐dimensional (0‐D) model has been applied to study the sources of hydrogen oxide radicals (HOx = HO2 + OH) in the tropical upper troposphere during the Pacific Exploratory Mission in the tropics (PEM‐Tropics B) aircraft mission over the South Pacific in March–April 1999. Observations made across the Southern Pacific Convergence Zone (SPCZ) and the southern branch of the Intertropical Convergence Zone (ITCZ) provided the opportunity to contrast the relative contributions of different sources of HOx, in a nitrogen oxide radical (NOx)‐limited regime, in relatively pristine tropical air. The primary sources of HOx vary significantly along the flight track, in correlation with the supply of water vapor. The latitudinal variation of HOx sources is found to be controlled also by the levels of NOx and primary HOx production rates P(HOx). Budget calculations in the 8‐ to 12‐km altitude range show that the reaction O(1D) + H2O is a major HOx source in the cloud region traversed by the aircraft, including SPCZ and the southern branch of the ITCZ. Production from acetone becomes significant in drier region south of 20°S and can become dominant where water vapor mixing ratios lie under 200 ppmv. Over the SPCZ region, in the cloud outflow, CH3 OOH transported by convection accounts for 22% to 64% of the total primary source. Oxidation of methane amplifies the primary HOx source by 1–1.8 in the dry regions

A case study of transport of tropical marine boundary layer and lower tropospheric air masses to the northern midlatitude upper troposphere

Low‐ozone (ppbv) air masses were observed in the upper troposphere in northern midlatitudes over the eastern United States and the North Atlantic Ocean on several occasions in October 1997 during the NASA Subsonic Assessment, Ozone and Nitrogen Oxide Experiment (SONEX) mission. Three cases of low‐ozone air masses were shown to have originated in the tropical Pacific marine boundary layer or lower troposphere and advected poleward along a warm conveyor belt during a synoptic‐scale disturbance. The tropopause was elevated in the region with the low‐ozone air mass. Stratospheric intrusions accompanied the disturbances. On the basis of storm track and stratospheric intrusion climatologies, such events appear to be more frequent from September through March than the rest of the year

Carboxylic acids in the rural continental atmosphere over the eastern United States during the Shenandoah Cloud and Photochemistry Experiment

The Shenandoah Cloud and Photochemistry Experiment (SCAPE) was conducted during September 1990 in the rural continental atmosphere at a mountain top site (1014 m) in Shenandoah National Park, Virginia. We report here the extensive set of trace gas measurements performed during clear sky periods of SCAPE, with particular focus on the carboxylic acids, formic, acetic, and pyruvic. Median mixing ratios were 5.4 and 2.1 parts per billion by volume (ppbv) for formic and acetic acid, respectively, and they did not exhibit the diurnal variation characteristic of low-elevation sites. Mixing ratios of formic acid often approached or exceeded 10 ppbv, which are the largest values yet reported for the nonurban troposphere. Over the rural eastern United States, formic and acetic acid appear to have significant nonphotochemical sources. Secondary production from suspected pathways appears to be relatively unimportant. The observed lack of correlation between formic and acetic acid with peroxide species argues against a significant source from permutation reactions of peroxy radicals. In addition, model calculations using the SCAPE data indicate minimal production of carboxylics from olefin/O3 oxidation reactions. The tight correlation (r2 = 0.88) between mixing ratios of formic and acetic acid is strongly suggestive of a commonality in their sources. The seasonal cycle of carboxylic acids in the atmosphere and precipitation over the eastern United States is evidence that combustion emissions are not a principal source of these species. It appears that direct biogenic emissions from vegetation and soils cannot be ruled out as important sources. In particular, the correlation between the seasonal variation of formic and acetic acid and the ambient temperature is consistent with a soil microbial source. Similar conclusions were reached for pyruvic acid, with its mixing ratio ranging 4–266 parts per trillion by volume (pptv) (median = 63) and most likely supported by biogenic emissions and possibly photochemical sources.Engineering and Applied Science

Search for Higgs Bosons in e+e- Collisions at 183 GeV

The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal

A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal

Large-scale ozone and aerosol distributions, air mass characteristics, and ozone fluxes over the western Pacific Ocean in late winter/early spring

Large‐scale measurements of ozone (O3) and aerosol distributions were made from the NASA DC‐8 aircraft during the Transport and Chemical Evolution over the Pacific (TRACE‐P) field experiment conducted in February–April 2001. Remote measurements were made with an airborne lidar to provide O3 and multiple‐wavelength aerosol backscatter profiles from near the surface to above the tropopause along the flight track. In situ measurements of O3, aerosols, and a wide range of trace gases were made onboard the DC‐8. Five‐day backward trajectories were used in conjunction with the O3 and aerosol distributions on each flight to indicate the possible origin of observed air masses, such as from biomass burning regions, continental pollution, desert regions, and oceanic regions. Average latitudinal O3 and aerosol scattering ratio distributions were derived from all flights west of 150°E, and these distributions showed the average latitude and altitude dependence of different dynamical and chemical processes in determining the atmospheric composition over the western Pacific. TRACE‐P (TP) showed an increase in the average latitudinal distributions of both O3 and aerosols compared to PEM‐West B (PWB), which was conducted in February–March 1994. O3, aerosol, and potential vorticity levels were used to identify nine air mass types and quantify their frequency of occurrence as a function of altitude. This paper discusses the characteristics of the different air mass types encountered during TP and compares them to PWB. These results confirmed that most of the O3 increase in TP was due to photochemistry. The average latitudinal eastward O3 flux in the western Pacific during TP was found to peak near 32°N with a total average O3 flux between 14 and 46°N of 5.2 Tg/day. The eastward total CO flux was calculated to be 2.2 Tg‐C/day with ∼6% estimated from Asia. The Asian flux of CO2 and CH4 was estimated at 4.9 and 0.06 Tg‐C/day