90 research outputs found
Solar X-ray Flare Hazards on the Surface of Mars
Putative organisms on the Martian surface would be exposed to potentially
high doses of ionizing radiation during strong solar X-ray flares. We
extrapolate the observed flare frequency-energy release scaling relation to
releases much larger than seen so far for the sun, an assumption supported by
observations of flares on other solar- and subsolar-mass main sequence stars.
We calculate the surficial reprocessed X-ray spectra using a Monte Carlo code
we have developed. Biological doses from indirect genome damage are calculated
for each parameterized flare spectrum by integration over the X-ray opacity of
water. We estimate the mean waiting time for solar flares producing a given
biological dose of ionizing radiation on Mars and compare with lethal dose data
for a wide range of terrestrial organisms. These timescales range from decades
for significant human health risk to 0.5 Myr for D. radiodurans lethality. Such
doses require total flare energies of 10^33--10^38 erg, the lower range of
which has been observed for other stars. Flares are intermittent bursts, so
acute lethality will only occur on the sunward hemisphere during a sufficiently
energetic flare, unlike low-dose-rate, extended damage by cosmic rays. We
estimate the soil and CO_2 ice columns required to provide 1/e shielding as
4--9 g cm^-2, depending on flare mean energy and atmospheric column density.
Topographic altitude variations give a factor of two variation in dose for a
given flare. Life in ice layers that may exist ~ 100 g cm^-2 below the surface
would be well protected.Comment: To be published in Planetary and Space Science; 33 pages, 3 figure
Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis
Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors
Risks due to X-ray Flares during Astronaut Extravehicular Activity
Solar hard X-ray flares can expose astronauts on lunar and deep space
extravehicular activities (EVAs) to dangerous acute biological doses. We
combine calculations of radiative transfer through shielding materials with
subsequent transfer through tissue to show that hazardous doses, taken as >=
0.1 Gy, should occur with a probability of about 10% per 100 hours of
accumulated EVA inside current spacesuits. The rapid onset and short duration
of X-ray flares and the lack of viable precursor events require strategies for
quick retreat, in contrast to solar proton events, which usually take hours to
deliver significant fluence and can often be anticipated by flares or other
light-speed precursors. Our results contrast with the view that only particle
radiation poses dangers for human space exploration. Heavy-element shields
provide the most efficient protection from X-ray flares, since X-rays produce
no significant secondary radiation. We calculate doses due to X-ray flares
behind aluminum shields and estimate the required shield masses to accompany
EVA rovers.Comment: 8 pages, 2 figures; to be published in Space Weathe
Novel HIV-1 Knockdown Targets Identified by an Enriched Kinases/Phosphatases shRNA Library Using a Long-Term Iterative Screen in Jurkat T-Cells
HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA) library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies
Insights into household transmission of SARS-CoV-2 from a population-based serological survey
Understanding the risk of infection from household- and community-exposures and the transmissibility of asymptomatic infections is critical to SARS-CoV-2 control. Limited previous evidence is based primarily on virologic testing, which disproportionately misses mild and asymptomatic infections. Serologic measures are more likely to capture all previously infected individuals. We apply household transmission models to data from a cross-sectional, household-based population serosurvey of 4,534 people ≥5 years from 2,267 households enrolled April-June 2020 in Geneva, Switzerland. We found that the risk of infection from exposure to a single infected household member aged ≥5 years (17.3%,13.7-21.7) was more than three-times that of extra-household exposures over the first pandemic wave (5.1%,4.5-5.8). Young children had a lower risk of infection from household members. Working-age adults had the highest extra-household infection risk. Seropositive asymptomatic household members had 69.4% lower odds (95%CrI,31.8-88.8%) of infecting another household member compared to those reporting symptoms, accounting for 14.5% (95%CrI, 7.2-22.7%) of all household infections
CRYSTAL STRUCTURE OF THE C89A_C113A GMP SYNTHETASE INACTIVE DOUBLE MUTANT FROM PLASMODIUM FALCIPARUM
Structure of the PL6 family alginate lyase Patl3640 from Pseudoalteromonas atlantica T6c in complex with 4-deoxy-L-erythro-5-hexoseulose uronic acid
Structure of the PL6 family alginate lyase Patl3640 from Pseudoalteromonas atlantica T6c
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