Marco Polo: near Earth object sample return mission

Marco Polo is a joint European-Japanese mission of sample return from a Near Earth Object. The Marco Polo proposal was submitted to ESA on July 2007 in the framework of the Cosmic Vision 2015-2025 context, and on October 2007 passed the first evaluation process. The primary objectives of this mission is to visit a primitive NEO, belonging to a class that cannot be related to known meteorite types, to characterize it at multiple scales, and to bring samples back to Earth. Marco Polo will give us the first opportunity for detailed laboratory study of the most primitive materials that formed the planets. This will allow us to improve our knowledge on the processes which governed the origin and early evolution of the Solar System, and possibly of the life on Earth

A cryogenic liquid-mirror telescope on the moon to study the early universe

We have studied the feasibility and scientific potential of zenith observing liquid mirror telescopes having 20 to 100 m diameters located on the moon. They would carry out deep infrared surveys to study the distant universe and follow up discoveries made with the 6 m James Webb Space Telescope (JWST), with more detailed images and spectroscopic studies. They could detect objects 100 times fainter than JWST, observing the first, high-red shift stars in the early universe and their assembly into galaxies. We explored the scientific opportunities, key technologies and optimum location of such telescopes. We have demonstrated critical technologies. For example, the primary mirror would necessitate a high-reflectivity liquid that does not evaporate in the lunar vacuum and remains liquid at less than 100K: We have made a crucial demonstration by successfully coating an ionic liquid that has negligible vapor pressure. We also successfully experimented with a liquid mirror spinning on a superconducting bearing, as will be needed for the cryogenic, vacuum environment of the telescope. We have investigated issues related to lunar locations, concluding that locations within a few km of a pole are ideal for deep sky cover and long integration times. We have located ridges and crater rims within 0.5 degrees of the North Pole that are illuminated for at least some sun angles during lunar winter, providing power and temperature control. We also have identified potential problems, like lunar dust. Issues raised by our preliminary study demand additional in-depth analyses. These issues must be fully examined as part of a scientific debate we hope to start with the present article.Comment: 35 pages, 11 figures. To appear in Astrophysical Journal June 20 200

Marco Polo: A near Earth object sample return mission

From Introduction: MARCO POLO is a joint European-Japanese sample return mission to a Near-Earth Object. In late 2007 this mission was selected by ESA, in the framework of COSMIC VISION 2015-2025, for an assessment scheduled to last until mid 2009. This Euro-Asian mission will go to a primitive Near-Earth Object (NEO), such as a C or D type asteroid. The spacecraft will rendezvous with the object, and over an extended period scientifically characterize it at multiple scales and bring samples back to Earth for detailed scientific investigation

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity

Attenuation and Restoration of Severe Acute Respiratory Syndrome Coronavirus Mutant Lacking 2'-O-Methyltransferase Activity

The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern respiratory syndrome CoV (MERS-CoV) underscores the importance of understanding critical aspects of CoV infection and pathogenesis. Despite significant insights into CoV cross-species transmission, replication, and virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification of SARS-CoV NSP16 as a viral 2′-O-methyltransferase (2′-O-MTase) led to the possibility of utilizing this pathway to both attenuate SARS-CoV infection and develop novel therapeutic treatment options. Mutations were introduced into SARS-CoV NSP16 within the conserved KDKE motif and effectively attenuated the resulting SARS-CoV mutant viruses both in vitro and in vivo. While viruses lacking 2′-O-MTase activity had enhanced sensitivity to type I interferon (IFN), they were not completely restored in their absence in vivo. However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2′-O RNA, resulted in restored replication and virulence of the dNSP16 mutant virus. Finally, using the mutant as a live-attenuated vaccine showed significant promise for possible therapeutic development against SARS-CoV. Together, the data underscore the necessity of 2′-O-MTase activity for SARS-CoV pathogenesis and identify host immune pathways that mediate this attenuation. In addition, we describe novel treatment avenues that exploit this pathway and could potentially be used against a diverse range of viral pathogens that utilize 2′-O-MTase activity to subvert the immune system

Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus

Cross-hemispheric transport of Central African biomass burning pollutants: implications for downwind ozone production

Pollutant plumes with enhanced concentrations of trace gases and aerosols were observed over the southern coast of West Africa during August 2006 as part of the AMMA wet season field campaign. Plumes were observed both in the mid and upper troposphere. In this study we examined the origin of these pollutant plumes, and their potential to photochemically produce ozone (O3) downwind over the Atlantic Ocean. Their possible contribution to the Atlantic O3 maximum is also discussed. Runs using the BOLAM mesoscale model including biomass burning carbon monoxide (CO) tracers were used to confirm an origin from central African biomass burning fires. The plumes measured in the mid troposphere (MT) had significantly higher pollutant concentrations over West Africa compared to the upper tropospheric (UT) plume. The mesoscale model reproduces these differences and the two different pathways for the plumes at different altitudes: transport to the north-east of the fire region, moist convective uplift and transport to West Africa for the upper tropospheric plume versus north-west transport over the Gulf of Guinea for the mid-tropospheric plume. Lower concentrations in the upper troposphere are mainly due to enhanced mixing during upward transport. Model simulations suggest that MT and UT plumes are 16 and 14 days old respectively when measured over West Africa. The ratio of tracer concentrations at 600 hPa and 250 hPa was estimated for 14–15 August in the region of the observed plumes and compares well with the same ratio derived from observed carbon dioxide (CO2) enhancements in both plumes. It is estimated that, for the period 1–15 August, the ratio of Biomass Burning (BB) tracer concentration transported in the UT to the ones transported in the MT is 0.6 over West Africa and the equatorial South Atlantic. Runs using a photochemical trajectory model, CiTTyCAT, initialized with the observations, were used to estimate in-situ net photochemical O3 production rates in these plumes during transport downwind of West Africa. The mid-troposphere plume spreads over altitude between 1.5 and 6 km over the Atlantic Ocean. Even though the plume was old, it was still very photochemically active (mean net O3 production rates over 10 days of 2.6 ppbv/day and up to 7 ppbv/day during the first days) above 3 km especially during the first few days of transport westward. It is also shown that the impact of high aerosol loads in the MT plume on photolysis rates serves to delay the peak in modelled O3 concentrations. These results suggest that a significant fraction of enhanced O3 in mid-troposphere over the Atlantic comes from BB sources during the summer monsoon period. According to simulated occurrence of such transport, BB may be the main source for O3 enhancement in the equatorial south Atlantic MT, at least in August 2006. The upper tropospheric plume was also still photochemically active, although mean net O3 production rates were slower (1.3 ppbv/day). The results suggest that, whilst the transport of BB pollutants to the UT is variable (as shown by the mesoscale model simulations), pollution from biomass burning can make an important contribution to additional photochemical production of O3 in addition to other important sources such as nitrogen oxides (NOx) from lightning

Folyóirat vagy gyűjteményes kötet? (Csokonai Diétai Magyar Múzsája)

BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Individual influenza A virus mRNAs show differential dependence on cellular NXF1/TAP for their nuclear export

The influenza A virus RNA-dependent RNA polymerase produces capped and polyadenylated mRNAs in the nucleus of infected cells that resemble mature cellular mRNAs, but are made by very different mechanisms. Furthermore, only two of the 10 viral protein-coding mRNAs are spliced: most are intronless, while two contain unremoved introns. The mechanism(s) by which any of these mRNAs are exported from the nucleus is uncertain. To probe the involvement of the primary cellular mRNA export pathway, we treated cells with siRNAs against NXF1, Aly or UAP56, or with the drug 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB), an inhibitor of RNA polymerase II phosphorylation previously shown to inhibit nuclear export of cellular mRNA as well as influenza virus segment 7 mRNAs. Depletion of NXF1 or DRB treatment had similar effects, inhibiting the nuclear export of several of the viral mRNAs. However, differing degrees of sensitivity were seen, depending on the particular segment examined. Intronless HA mRNA and spliced M2 or unspliced M1 transcripts (all encoding late proteins) showed a strong requirement for NXF1, while intronless early gene mRNAs, especially NP mRNA, showed the least dependency. Depletion of Aly had little effect on viral mRNA export, but reduction of UAP56 levels strongly inhibited trafficking and/or translation of the M1, M2 and NS1 mRNAs. Synthesis of NS2 from the spliced segment 8 transcript was, however, resistant. We conclude that influenza A virus co-opts the main cellular mRNA export pathway for a subset of its mRNAs, including most but not all late gene transcripts