Small satellites for space science : A COSPAR scientific roadmap

This is a COSPAR roadmap to advance the frontiers of science through innovation and international collaboration using small satellites. The world of small satellites is evolving quickly and an opportunity exists to leverage these developments to make scientific progress. In particular, the increasing availability of low-cost launch and commercially available hardware provides an opportunity to reduce the overall cost of science missions. This in turn should increase flight rates and encourage scientists to propose more innovative concepts, leading to scientific breakthroughs. Moreover, new computer technologies and methods are changing the way data are acquired, managed, and processed. The large data sets enabled by small satellites will require a new paradigm for scientific data analysis. In this roadmap we provide several examples of long-term scientific visions that could be enabled by the small satellite revolution. For the purpose of this report, the term “small satellite” is somewhat arbitrarily defined as a spacecraft with an upper mass limit in the range of a few hundred kilograms. The mass limit is less important than the processes used to build and launch these satellites. The goal of this roadmap is to encourage the space science community to leverage developments in the small satellite industry in order to increase flight rates, and change the way small science satellites are built and managed. Five recommendations are made; one each to the science community, to space industry, to space agencies, to policy makers, and finally, to COSPAR

Defective oligomerization of arylsulfatase A as a cause of its instability in lysosomes and metachromatic leukodystrophy

Bulow von R, Schmidt B, Dierks T, et al. Defective oligomerization of arylsulfatase A as a cause of its instability in lysosomes and metachromatic leukodystrophy. JOURNAL OF BIOLOGICAL CHEMISTRY. 2002;277(11):9455-9461.In one of the most common mutations causing metachromatic leukodystrophy, the P426L-allele of arylsulfatase A (ASA), the deficiency of ASA results from its instability in lysosomes. Inhibition of lysosomal cysteine proteinases protects the P426L-ASA and restores the sulfatide catabolism in fibroblasts of the patients. P426L-ASA, but not wild type ASA, was cleaved by purified cathepsin L at threonine 421 yielding 54- and 9-kDa fragments. X-ray crystallography at 2.5-Angstrom resolution showed that cleavage is not due to a difference in the protein fold that would expose the peptide bond following threonine 421 to proteases. Octamerization, which depends on protonation of Glu-424, was impaired for P426L-ASA. The mutation lowers the pH for the octamer/ dimer equilibrium by 0.6 pH units from pH 5.8 to 5.2. A second oligomerization mutant (ASA-A464R) was generated that failed to octamerize even at pH 4.8. A464R-ASA was degraded in lysosomes to catalytically active 54-kDa intermediate. In cathepsin L-deficient fibroblasts, degradation of P426L-ASA and A464R-ASA to the 54-kDa fragment was reduced, while further degradation was blocked. This indicates that defective oligomerization of ASA allows degradation of ASA to a catalytically active 54-kDa intermediate by lysosomal cysteine proteinases, including cathepsin L. Further degradation of the 54-kDa intermediate critically depends on cathepsin L and is modified by the structure of the 9-kDa cleavage product

Source attribution of community-acquired cases of Legionnaires’ disease–results from the German LeTriWa study

Introduction Sources of infection of most cases of community-acquired Legionnaires’ disease (CALD) are unknown. Objective Identification of sources of infection of CALD. Setting Berlin; December 2016–May 2019. Participants Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls. Main outcome measure Percentage of cases of CALD with attributed source of infection. Methods Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)). Results Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25–93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed. Conclusion Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.Peer Reviewe