Hindlimb unloading, a physiological model of microgravity, modifies the murine bone marrow IgM repertoire in a similar manner as aging but less strongly.

BACKGROUND: The spaceflight environment is an extreme environment that affects the immune system of approximately 50% of astronauts. With planned long-duration missions, such as the deployment of the Lunar Gateway and possible interplanetary missions, it is mandatory to determine how all components of the immune system are affected, which will allow the establishment of countermeasures to preserve astronaut health. However, despite being an important component of the immune system, antibody-mediated humoral immunity has rarely been investigated in the context of the effects of the space environment. It has previously been demonstrated that 30 days aboard the BION-M1 satellite and 21 days of hindlimb unloading (HU), a model classically used to mimic the effects of microgravity, decrease murine B lymphopoiesis. Furthermore, modifications in B lymphopoiesis reported in young mice subjected to 21 days of HU were shown to be similar to those observed in aged mice (18-22 months). Since the primary antibody repertoire composed of IgM is created by V(D) J recombination during B lymphopoiesis, the objective of this study was to assess the degree of similarity between changes in the bone marrow IgM repertoire and in the V(D)J recombination process in 2.5-month-old mice subjected to 21 days of HU and aged (18 months) mice. RESULTS: We found that in 21 days, HU induced changes in the IgM repertoire that were approximately 3-fold less than those in aged mice, which is a rapid effect. Bone remodeling and epigenetics likely mediate these changes. Indeed, we previously demonstrated a significant decrease in tibial morphometric parameters from day 6 of HU and a progressive reduction in these parameters until day 21 of HU, and it has been shown that age and microgravity induce epigenetic changes. CONCLUSION: These data reveal novel immune changes that are akin to advanced aging and underline the importance of studying the effects of spaceflight on antibody-mediated humoral immunity.

Next generation of astronauts or ESA astronaut 2.0 concept and spotlight on immunity.

Although we have sent humans into space for more than 50 years, crucial questions regarding immune response in space conditions remain unanswered. There are many complex interactions between the immune system and other physiological systems in the human body. This makes it difficult to study the combined long-term effects of space stressors such as radiation and microgravity. In particular, exposure to microgravity and cosmic radiation may produce changes in the performance of the immune system at the cellular and molecular levels and in the major physiological systems of the body. Consequently, abnormal immune responses induced in the space environment may have serious health consequences, especially in future long-term space missions. In particular, radiation-induced immune effects pose significant health challenges for long-duration space exploration missions with potential risks to reduce the organism's ability to respond to injuries, infections, and vaccines, and predispose astronauts to the onset of chronic diseases (e.g., immunosuppression, cardiovascular and metabolic diseases, gut dysbiosis). Other deleterious effects encountered by radiation may include cancer and premature aging, induced by dysregulated redox and metabolic processes, microbiota, immune cell function, endotoxin, and pro-inflammatory signal production1,2. In this review, we summarize and highlight the current understanding of the effects of microgravity and radiation on the immune system and discuss knowledge gaps that future studies should address.

Long-duration head-down tilt bed rest confirms the relevance of the neutrophil to lymphocyte ratio and suggests coupling it with the platelet to lymphocyte ratio to monitor the immune health of astronauts.

The identification of safe and easily-determined-inflight biomarkers to monitor the immune system of astronauts is mandatory to ensure their well-being and the success of the missions. In this report, we evaluated the relevance of two biomarkers whose determination could be easily implemented in a spacecraft in the near future by using bedridden volunteers as a ground-based model of the microgravity of spaceflight. Our data confirm the relevance of the neutrophil to lymphocyte ratio (NLR) and suggest platelet to lymphocyte ratio (PLR) monitoring to assess long-lasting immune diseases. We recommend coupling these ratios to other biomarkers, such as the quantification of cytokines and viral load measurements, to efficiently detect immune dysfunction, determine when countermeasures should be applied to promote immune recovery, prevent the development of disease, and track responses to treatment.

Monitoring of freshwater toxins in European environmental waters by using novel multi-detection methods.

Monitoring the quality of freshwater is an important issue for public health. In the context of the European project µAqua, 150 samples were collected from several waters in France, Germany, Ireland, Italy, and Turkey for 2 yr. These samples were analyzed using 2 multitoxin detection methods previously developed: a microsphere-based method coupled to flow-cytometry, and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The presence of microcystins, nodularin, domoic acid, cylindrospermopsin, and several analogues of anatoxin-a (ATX-a) was monitored. No traces of cylindrospermopsin or domoic acid were found in any of the environmental samples. Microcystin-LR and microcystin-RR were detected in 2 samples from Turkey and Germany. In the case of ATX-a derivatives, 75% of samples contained mainly H2 -ATX-a and small amounts of H2 -homoanatoxin-a, whereas ATX-a and homoanatoxin-a were found in only 1 sample. These results confirm the presence and wide distribution of dihydro derivatives of ATX-a toxins in European freshwaters. Environ Toxicol Chem 2017;36:645-654. © 2016 SETAC.

Two-Year Monitoring of Water Samples from Dam of Iskar and the Black Sea, Bulgaria, by Molecular Analysis: Focus on Mycobacterium spp.

The coast of the Bulgarian Black Sea is a popular summer holiday destination. The Dam of Iskar is the largest artificial dam in Bulgaria, with a capacity of 675 million m3. It is the main source of tap water for the capital Sofia and for irrigating the surrounding valley. There is a close relationship between the quality of aquatic ecosystems and human health as many infections are waterborne. Rapid molecular methods for the analysis of highly pathogenic bacteria have been developed for monitoring quality. Mycobacterial species can be isolated from waste, surface, recreational, ground and tap waters and human pathogenicity of nontuberculose mycobacteria (NTM) is well recognized. The objective of our study was to perform molecular analysis for key-pathogens, with a focus on mycobacteria, in water samples collected from the Black Sea and the Dam of Iskar. In a two year period, 38 water samples were collected-24 from the Dam of Iskar and 14 from the Black Sea coastal zone. Fifty liter water samples were concentrated by ultrafiltration. Molecular analysis for 15 pathogens, including all species of genus Mycobacterium was performed. Our results showed presence of Vibrio spp. in the Black Sea. Rotavirus A was also identified in four samples from the Dam of Iskar. Toxigenic Escherichia coli was present in both locations, based on markers for stx1 and stx2 genes. No detectable amounts of Cryptosporidium were detected in either location using immunomagnetic separation and fluorescence microscopy. Furthermore, mass spectrometry analyses did not detect key cyanobacterial toxins. On the basis of the results obtained we can conclude that for the period 2012-2014 no Mycobacterium species were present in the water samples. During the study period no cases of waterborne infections were reported.

Health risk assessment related to waterborne pathogens from the river to the tap.

A two-year monitoring program of Cryptosporidium parvum oocysts, Giardia duodenalis cysts, Escherichia coli, Clostridium perfringens spores and adenovirus was conducted in three large rivers in France used for recreational activities and as a resource for drinking water production. Fifty-liter river water and one thousand-liter tap water samples were concentrated using hollow-fiber ultrafiltration and analyzed by molecular biology or laser-scanning cytometry. In order to evaluate watershed land use influence on microorganism concentration changes, occurrence and seasonality of microorganisms were studied. The highest concentrations of protozoan parasites and C. perfringens were found for one of the three sites, showing a high proportion of agricultural territories, forests and semi-natural environments, which may be partly attributable to soil leaching due to rainfall events. On the contrary, the highest concentrations of adenoviruses were found at the two other sites, probably due to strong urban activities. Health risk assessment was evaluated for each waterborne pathogen regarding exposure during recreational activities (for a single or five bathing events during the summer). The calculated risk was lower than 0.5% for parasites and varied from 1% to 42% for adenovirus. A theoretical assessment of microorganism removal during the drinking water treatment process was also performed, and it showed that an absence of microorganisms could be expected in finished drinking water. This hypothesis was confirmed since all tested tap water samples were negative for each studied microorganism, resulting in a risk for drinking water consumption lower than 0.01% for parasites and lower than 0.5% for adenovirus.

Acidophilic microbial communities catalyzing sludge bioleaching monitored by fluorescent in situ hybridization.

Biological autotrophic sulfur oxidation processes have been proposed to remove heavy metals from wastewater treatment sludge by bioleaching. We made a characterization of the microbial population in batch and continuous sludge bioleaching reactors using fluorescent in situ hybridization of fluorescently-labeled oligonucleotidic probes targeting rRNA in a 'top to bottom approach'. Batch incubations of sludge with 0.2% (w/v) elemental sulfur resulted in a pH value of 5. Alpha-Proteobacteria hybridizing with probe ALF1b were dominant in this incubation. Members of the Acidophilium-group (hybridizing with probe Acdp821) of Nitrospira/Leptospirillum phylum (Ntspa712 probe) and from the archaeal domain (ARCH915) were also detected. When sludge was incubated with 1% elemental sulfur in batch or continuous reactor experiments, final pH values were always below 2. Active microbial communities consisted almost exclusively of gamma-Proteobacteria (hybridizing with probe GAM42a). However, further hybridization experiments with probe Thio820 targeting Acidithiobacillus ferroxidans and Acidithiobacillus thioxidans gave negative results. A new probe, named THIO181, encompassing all known members of the genus was designed. Hybridization perfomed with THIO181 and GAM42a showed a perfect co-localization of the hybridization signals. Further hybridization experiments with probe THIO181 and THC642, specific for the species Acidithiobacillus caldus, confirmed that this bacteria was largely responsible for the sulfur oxidation reaction in our acidophilic sludge bioleaching reactors.