222 results on '"S Baatout"'
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2. PO-1000: Effect of X-rays and carbon ions on cell survival and expression of Hh pathway genes in cancer cells
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Sofie Isebaert, A. Gonnissen, K. Konings, M. Moreels, A. Suetens, Karin Haustermans, and S. Baatout
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chemistry ,Oncology ,Radiology Nuclear Medicine and imaging ,Cancer cell ,chemistry.chemical_element ,Radiology, Nuclear Medicine and imaging ,Hematology ,Molecular biology ,Carbon ,Gene ,Cell survival ,Ion - Published
- 2016
- Full Text
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3. Augmentation of the number of nucleolar organizer regions in human megakaryocyte cell lines after induction of polyploidization by a microtubule inhibitor
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Silver Staining ,Clinical Biochemistry ,Cell ,Cell Count ,Microtubules ,Biochemistry ,Polyploidy ,Blood cell ,chemistry.chemical_compound ,Megakaryocyte ,Leukemia, Megakaryoblastic, Acute ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Nucleolus Organizer Region ,Tumor Cells, Cultured ,medicine ,Protein biosynthesis ,Humans ,Colchicine ,Genetics ,biology ,Proteins ,food and beverages ,General Medicine ,Molecular biology ,medicine.anatomical_structure ,Tubulin ,chemistry ,Cell culture ,biology.protein ,Nucleolus organizer region ,Megakaryocytes ,Cell Nucleolus - Abstract
Megakaryocyte polyploidization is an advantageous and regulated mechanism that leads to an increase in platelet production. In megakaryocytic cell lines, polyploidization can be obtained by using colchicine, an inhibitor of the tubulin spindle. The nucleolar organizer regions (AgNORs) are parts of nucleolar DNA transcribed into ribosomal RNA and are detected by the silver-staining technique. Their number is proportional to protein synthesis.To estimate protein synthesis in polyploid megakaryocytes, AgNORs are measured in three cell lines with megakaryocyte properties (DAMI, HEL and K562) after a 4-day culture in the presence or absence of colchicine. The mean number of AgNORs per cell was 16+/-4 (mean+/-SEM), 24+/-3 and 14+/-3 for DAMI, HEL and K-562 cell lines respectively. The addition of colchicine (10 ng mL[-1]) significantly increased the number of AgNORs per cell (DAMI 556%, HEL 338% and K-562 300% of controls, P0.05 using the t-test). Moreover, the number of nucleoles per cell after the addition of colchicine was augmented significantly (DAMI 246%; HEL 237% and K-562 148% of controls, P0.05 using the t-test). The total protein content estimated by Bradford's method increased significantly to 226%, 215% and 304% of controls in DAMI, HEL and K562 respectively (P005 using the t-test). After treatment with colchicine, the endomitotic index (EI) [mean of (log2 DNA content expressed in N)-1] measured by flow cytometry (and reflecting ploidy) increased to 234%, 255% and 301%, respectively, in DAMI, HEL and K-562 cell lines (P0.05 using the t-test). Concomitantly, the number of AgNORs per unit of DNA increased in the DAMI and HEL cell lines (P0.05 using the t-test) from 48+/-8 and 39+/-5, respectively, to 79+/-11 and 61+/-10. In contrast, the number of nucleoles and the total protein content per endomitotic index were not affected by colchicine (P0.05 using the t-test), but the number of nucleoles per endomitotic index of DAMI cells was affected.The increase in the number of the NORs induced by an agent known to stimulate polyploidization of megakaryocytic cell lines suggests that polyploidization occurs by a proportional increase in protein synthesis per DNA unit.
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- 1998
4. Cytogenetic effects of X-rays in the guinea pig female germ cells. I. The immature oocyte
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P, Jacquet, L, de Saint-Georges, J, Buset, S, Baatout, J, Vankerkom, and L, Baugnet-Mahieu
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Chromosome Aberrations ,Male ,X-Rays ,Health, Toxicology and Mutagenesis ,Guinea Pigs ,Dose-Response Relationship, Radiation ,Meiosis ,Animals, Newborn ,Pregnancy ,Oocytes ,Genetics ,Animals ,Humans ,Female ,Metaphase - Abstract
In female mammals, the immature oocyte is the germ cell most at risk, from the genetic point of view. We have previously shown that ovaries of newborn guinea pigs contain a great majority of immature oocytes and small numbers of maturing oocytes. At this time, all immature oocytes are in a typical diplotene stage, comparable to that of the human resting oocyte. Furthermore, the LD50 of the guinea pig oocytes is about 4 Gy, like that of human oocytes. Consequently, performing genetic studies on guinea pig oocytes irradiated just after birth constitutes a very useful approach to predict the mutational response of the human resting oocyte. Female guinea pigs were X-irradiated with 1 or 2 Gy within 24 h of birth, and their meiotically competent oocytes were collected and cultured to the metaphase I stage, 1 year after treatment, ensuring that all oocytes were at the immature stage at the time of irradiation. The proportion of oocytes that showed chromosome aberrations (breaks, fragments or interchanges) was only 1-2% Gy(-1). Although not definitive, these results provide support for a low risk in women from an exposure of the immature oocyte to low doses of radiation.
- Published
- 1997
5. Thrombopoietin
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S. Baatout
- Subjects
Mpl Ligand ,Physiology (medical) ,Hemostasis ,Biological property ,Immunology ,Regulator ,Platelet ,Hematology ,Biology ,Receptor ,Thrombopoietin - Abstract
The regulator of platelet count is believed to be thrombopoîetin (mpl ligand). It is thought to act on the megakaryocytic lineage affecting the proliferation of committed cells, the maturation of megakaryocytes and the blood platelet levels by activation of its receptor (the c-mpl). Recently, it has been purified and sequenced. Thrombopoîetin offers potential applications for treatment of thrombocytopenia.
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- 1997
6. SP-0610: Gene expression alterations to carbon ion and X-irradiation
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K. Konings, M. Moreels, and S. Baatout
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Carbon ion ,Oncology ,Radiology Nuclear Medicine and imaging ,Chemistry ,Gene expression ,Radiology, Nuclear Medicine and imaging ,Hematology ,Irradiation ,Molecular biology - Published
- 2016
7. PAEDIATRIC COMPUTED TOMOGRAPHY AND SUBSEQUENT CANCER: SETTING UP OF THE EUROPEAN PROJECT EPI-CT
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MO Bernier, I Thierry-Chef, Michael Hauptmann, E Cardis, Pearce, A Kesminiene, C Maccia, and S Baatout
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine ,General Earth and Planetary Sciences ,Cancer ,Computed tomography ,Radiology ,Ionising radiation exposure ,medicine.disease ,business ,General Environmental Science ,Paediatric patients - Abstract
Background and Aims The growing use of computed tomography (CT) scans for paediatric patients raises the question of a possible impact of ionising radiation exposure on leukaemia and other cancers....
- Published
- 2011
8. Annual meeting of the American Association for Cancer Research 12-16 April 1997, San Diego, CA, USA
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S Baatout
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Gerontology ,Genetics ,Molecular Medicine ,Biology ,Molecular Biology - Published
- 1998
9. The importance of cytoskeleton proteins in megakaryocyte spreading and platelet formation
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S Baatout
- Subjects
Blood Platelets ,Cellular differentiation ,Cell ,Cell Differentiation ,Hematology ,Biology ,In vitro ,Cell biology ,medicine.anatomical_structure ,Oncology ,Megakaryocyte ,Cytoplasm ,Immunology ,Cell Adhesion ,medicine ,Animals ,Humans ,Platelet ,sense organs ,skin and connective tissue diseases ,Cytoskeleton ,Cell adhesion ,Megakaryocytes - Abstract
The release of platelets into the circulation is preceded by considerable morphologic change of the parent megakaryocyte. The cell extends cytoplasmic processes into the venous sinusoids, which develop constrictions at intervals, revealing putative platelets. The pattern of cytoskeletal distribution changes during the spread of megakaryocytes in vitro. In this review, an attempt was made to summarize the data of the literature concerning the changes in the cytoskeletal pattern of megakaryocytes during their spreading and platelet formation.
- Published
- 1996
10. Space flight effects on bacterial physiology
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N M E J, Leys, L, Hendrickx, P, De Boever, S, Baatout, and M, Mergeay
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Bioreactors ,Bacteria ,Weightlessness ,Biofilms ,Gene Expression Regulation, Bacterial ,Space Flight ,Bacterial Physiological Phenomena ,Cosmic Radiation ,Weightlessness Simulation ,DNA Damage ,Signal Transduction - Abstract
The study of bacterial behavior under space flight conditions is highly important for the early detection of changes in bacterial communities and bacteria with medical, environmental, or life support consequences for survival of the crew in closed space environments. Although many species of prokaryotes have been studied in ground simulation facilities or have been flown in space flights, at present only few hard research data are available to predict the effects of cosmic radiation, microgravity, vibration and hypervelocity on microbial behavior in space flight. The results that are available tend to be fragmentary and often lack a classical, controlled experimental context to interpret them. Thus, many basic questions concerning the effects of space on microbial behavior have yet to be resolved.
- Published
- 2004
11. Cytometric methods to analyze radiation effects
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S, Baatout and H, Derradji
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Chromosome Aberrations ,Eukaryotic Cells ,Micronucleus Tests ,Cell Cycle ,Cytological Techniques ,Animals ,Humans ,Apoptosis ,Comet Assay ,Cytophotometry ,DNA ,Flow Cytometry ,In Situ Hybridization, Fluorescence - Abstract
Here, we review the most relevant cytometric methods currently used to analyze ionizing radiation effects. Particular interest has been devoted to the following methods: chromosomal aberrations, micronucleus assay, fluorescence in situ hybridization chromosome painting, comet assay, comet-FISH assay as well as flow cytometry.
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- 2004
12. Human megakaryocyte polyploidization is associated with a decrease in GPIIIA expression
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Polyploidy ,Purpura, Thrombocytopenic ,Antigens, CD ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Integrin beta3 ,Humans ,Platelet Membrane Glycoproteins ,Flow Cytometry ,Megakaryocytes ,Polycythemia Vera - Abstract
Megakaryocytes are platelet forming cells and are characterized by polyploidization, a phenomenon by which nuclear division occurs without corresponding cytoplasmic separation. Among the markers allowing to identify megakaryocytes, glycoprotein (GP) IIIa with GPIb and GPIIb are the most important. Using GPIIIa as a marker to recognize megakaryocytes in the bone marrow, we have estimated GPIIIa expression by flow cytometry in megakaryocyte populations from normal individuals and from patients with chronic myelogenous leukemia, immune thrombocytopenic purpura or polycythemia vera. We showed that the expression of GPIIIa is decreasing during megakaryocyte polyploidization in normal and pathological situations.
- Published
- 2000
13. The G and F contents in megakaryocyte cell lines after stimulation with phorbol myristate acetate
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Humans ,Tetradecanoylphorbol Acetate ,Flow Cytometry ,Megakaryocytes ,Actins ,Cells, Cultured - Abstract
Megakaryocyte polyploidization responds to platelet demand and results from the lack of cytoplasmic separation while the nucleus keeps dividing. In order to investigate the role of actin in the megakaryocyte polyploidization, phorbol myristate acetate (PMA, 5 x 10(-9) M), a differentiation marker known to induce megakaryocyte polyploidization, was added to human megakaryocytic cell lines (DAMI and HEL) and G, F and total actins were estimated by DNase I inhibition. After four days of culture in the presence of PMA, G actin contents in pg per 10(6) cells were 13.0 pg +/- 2.8 and 1.0 pg +/- 0.1 for unstimulated DAMI and HEL cells. F actin contents per 10(6) cells were 5.8 pg +/- 1.5 and 0.1 pg +/- 0.0 for DAMI and HEL cells. Addition of PMA for four days to culture significantly increased G actin contents (235% and 268% of controls) and F actin contents (234% and 394%), for DAMI and HEL cell lines, respectively (p0.05 by t-test). In contrast, G/F actin ratio was not affected (p0.05 by t-test) by PMA. DAMI cells from each ploidy classes were then sorted on an ELITE Coulter and assayed for actin content. While total actin, G actin and F actin per cell increased in polyploid cells cultured with PMA, there was a reduction in G, F and total actin contents per diploid equivalent when cells became polyploid. In conclusion, megakaryocyte polyploidization of these cell lines is not related to an unbalance between G and F actins but would be rather due at least partly to a defect in total actin production that could lead to a prevention of the formation of the constriction ring in telophase.
- Published
- 2000
14. Protein content and number of nucleolar organizer regions are enhanced during phorbol ester-induced differentiation of cultured human megakaryocytic cells
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Nucleolus Organizer Region ,Humans ,Tetradecanoylphorbol Acetate ,Cell Differentiation ,Platelet Membrane Glycoproteins ,Megakaryocytes ,Cells, Cultured - Abstract
In order to investigate the protein synthesis in megakaryocyte polyploidization, phorbol myristate acetate (PMA, 5 x 10(-9) M), a differentiation marker known to induce megakaryocyte polyploidization, was added to human megakaryocytic cell lines (DAMI, HEL and K562) and the expression of platelet/megakaryocytic integrins, the numbers of nucleolar organizer regions (AgNORs) and the total protein content were estimated. Following exposure of PMA, the expression of the platelet membrane glycoprotein GPIIIa and thrombospondin and transferrin receptors was augmented in the three cell lines. The number of AgNORs shifted from 16.4 +/- 4.3, 24.4 +/- 2.5 and 13.6 +/- 3.1 for unstimulated cells to 20.0 +/- 5.3, 38.7 +/- 7.9 and 16.8 +/- 2.3 for PMA-treated DAMI, HEL and K562 cells, respectively. Furthermore, after treatment with PMA, the numbers of AgNORs clusters or nucleoles increased significantly to 179%, 238% and 154% of controls in DAMI, HEL and K562 cell lines, respectively. Finally, addition of PMA culture for four days, significantly increased the protein contents to 153%, 171% and 254% of controls for DAMI, HEL and K562 cell lines, respectively (p0.05 by t-test). In conclusion, the increase in the total protein content and in the number of AgNORs by PMA, suggests that PMA-induced-megakaryocyte polyploidization occurs by enhanced protein production.
- Published
- 2000
15. Interaction between protein kinase C and actin in megakaryocyte polyploidization
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Polyploidy ,Cytochalasin B ,Leukemia, Megakaryoblastic, Acute ,Carcinogens ,Tumor Cells, Cultured ,Humans ,Tetradecanoylphorbol Acetate ,Microscopy, Phase-Contrast ,Flow Cytometry ,Megakaryocytes ,Actins ,Cell Division ,Protein Kinase C - Abstract
Megakaryocytes undergo a peculiar and irreversible program by which they become polyploid through repeated cycles of DNA synthesis without concomitant cell division. In order to study the possible concomitant role of protein kinase C and actin in megakaryocyte polyploidization, three cell lines (DAMI, HEL and K562), expressing some properties of the megakaryocytic lineage and known to differentiate into the megakaryocytic pathway in the presence of phorbol esters, were cultivated in the presence of phorbol myristate acetate alone (PMA, 5 x 10(-9) M, activator of protein kinase C, PKC) or concomitantly with cytochalasin B (2 micrograms/ml, inhibitor of actin polymerization). We have previously shown that DAMI, HEL and K562 cells in which actin polymerization was inhibited by cytochalasin B, acquired megakaryocytic properties in the way that they became polyploid, acquired a megakaryocytic phenotype and arrested proliferation (4). After four days of culture in the presence of PMA and cytochalasin B, the number of polyploid cells (estimated by flow cytometry) increased in comparison with control or PMA-treated cells. However, it was lower than in cytochalasin B-treated cells. Indeed, control cells predominantly diploid (2N) became polyploid with the appearance of 8N, 16N and 32N cells after addition of PMA, cytochalasin B or PMA + cytochalasin B. The endomitotic index (EI, as described in 5) which corresponds to the mean of (¿log2 DNA content expressed in N¿-1) was 0.5 +/- 0.1, 0.7 +/- 0.1 and 0.3 +/- 0.1 in control DAMI, HEL and K562 cells, respectively. The EI increased to 0.9 +/- 0.2; 1.0 +/- 0.2 and 0.4 + 0.1 in cells treated with PMA and to 1.6 +/- 0.3; 1.4 +/- 0, and 0.9 +/- 0.2 when PMA was added concomitantly to cytochalasin B. Total DNA estimated from the cell content and the percentage of cells present at each ploidy stage did not change in cytochalasin B-treated cells in comparison to control conditions. However, treatment of DAMI, HEL and K562 cells with PMA alone or concomitantly with cytochalasin B revealed that the total DNA content significantly decreased in these conditions. At last, treatment of the three cell lines with PMA alone or concomitantly with cytochalasin B for 4 days caused a complete inhibition of proliferation. In conclusion, the concomitant addition of PMA and cytochalasin B to the three cell lines lead to an augmentation of cell ploidy and to a cessation of proliferation. However, we did not observe any synergistic effect of the two compounds. The possible interaction between actin and protein kinase C is discussed in the paper.
- Published
- 2000
16. Analysis of megakaryocytes by flow cytometry
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Adult ,Male ,Ploidies ,Adolescent ,Antigens, CD ,Integrin beta3 ,Humans ,Female ,Platelet Membrane Glycoproteins ,Middle Aged ,Flow Cytometry ,Megakaryocytes ,Aged - Abstract
A flow cytofluorometric measurement of megakaryocyte ploidy has been adapted from Tomer's method. Briefly, bone marrow is aspirated through a medium containing theophyllin, prostaglandin-E1 and other antiaggregant agents. Megakaryocytes-enriched buffy coats are recovered. Megakaryocytes are then stained for GP IIIa coupled with FITC and for DNA (propidium iodide). A Becton Dickinson FACScan flow cytometer is used for measuring the ploidy distribution of GP IIIa positive cells. The method we developed presents several advantages. Firstly, the time required is greatly decreased in comparison with other studies. Secondly, the washing steps are limited in number allowing a diminution of the cell loss. Thirdly, the method ensures a better megakaryocyte preservation. Finally, selection of megakaryocytes by ploidy and expression of GP IIIa can be made easily because of the simultaneity of the two stainings as well as by the use of a precise gating on the flow cytometer. Based on these results, we conclude that the present method provides a better means for the isolation and analysis of human normal megakaryocytes. This technique has been applied to the analysis of megakaryocyte populations from patients with abnormal platelet counts. In chronic myeloid leukemia patients, analysis of ploidy distribution shows a shift toward the low ploidy while in patients with immune thrombocytopenic purpura, polycythemia vera and essential thrombocythemia the ploidy distributions are shifted toward the high ploidy.
- Published
- 1999
17. Endomitotic index of megakaryocytes measured by flow cytometry helps to diagnose hematological disorders with abnormal platelet counts
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Adult ,Male ,Purpura, Thrombocytopenic, Idiopathic ,Ploidies ,Adolescent ,Platelet Count ,Middle Aged ,Flow Cytometry ,Hematologic Diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Mitotic Index ,Humans ,Female ,Megakaryocytes ,Polycythemia Vera ,Aged ,Thrombocythemia, Essential - Abstract
Platelet production is a regulated phenomenon. Indeed, megakaryocyte volume is inversely correlated to the platelet count not only in normal individuals and immune thrombocytopenic purpura patients, but also, and surprisingly, in chronic myeloid leukemia patients. Patients with polycythemia vera and essential thrombocythemia are located outside this regression line. Herein, we describe morphometrical data confirmed by the flow cytometric measurement of the megakaryocyte endomitotic index (EI). The EI is a value which reflects the mean ploidy of megakaryocytes and corresponds to the mean of (¿log2 DNA content expressed in N¿-1). In this study, the megakaryocyte endomitotic index of 14 normal individuals was compared to those of chronic myeloid leukemia (CML) patients (n = 16), immune thrombocytopenic purpura (ITP) patients (n = 11), essential thrombocythemia (ET) patients (n = 10) and polycythemia vera (PV) patients (n = 12). The megakaryocyte EI was significantly lower in CML patients than in normal individuals. In contrast, in ET, PV and ITP patients, megakaryocyte EI was higher than in normal individuals. An inverse relationship between the endomitotic index estimated by flow cytometry and the mean megakaryocyte volume performed by morphometry was observed in normal individuals, CML and ITP patients. In conclusion, the endomitotic index is higher in ITP, ET and PV patients and lower in CML patients when compared to normal individuals and is an interesting tool which can help to diagnose rapidly hematological disorders with abnormal platelet counts.
- Published
- 1998
18. Induction and enhancement of normal human megakaryocyte polyploidization are concomitant with perturbation in the actin metabolism
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
- Subjects
Polyploidy ,Humans ,Bone Marrow Cells ,RNA, Messenger ,Megakaryocytes ,Actins ,Cell Division ,Cell Line ,Cell Size - Abstract
Megakaryocyte polyploidization results from the lack of cytoplasmic separation while the nucleus keeps dividing.To investigate the role of actin in the megakaryocyte polyploidization, three human cell lines with megakaryocytic properties (DAMI, HEL and K562) were incubated in the presence of cytochalasin B, an inhibitor of actin polymerization. These data were then compared with normal megakaryocytes.Compared with control conditions, cells cultured in the presence of cytochalasin B revealed an augmentation of cell size and ploidy and an arrest of cell proliferation. The expression of platelet membrane glycoproteins Ib, IIb/IIIa, IIIa and thrombospondin and transferrin receptors was augmented after treatment with cytochalasin B. Physiologically, the role of actin in inducing polyploidization could be related to an imbalance between G- and F-actins. To test this hypothesis, we measured G-, F- and total actin in cytochalasin B-treated cells. Actin was found to be increased significantly in cytochalasin B-treated DAMI and HEL cell lines. In contrast, the G/F-actin ratio was not affected by cytochalasin B. To confirm these actin changes in physiological megakaryocytopoiesis, G- and F-actin contents were then estimated in normal megakaryocytes. The G- and F-actin contents of megakaryocytes from eight normal patients exponentially decreased from 2 to 128n, whereas the total actin content per cell kept increasing. The G/F ratio was unaffected.Polyploidization of human megakaryocytes results from either a diminution of actin synthesis or an increased actin turnover, which in turn possibly abrogates the formation of the actin cleavage furrow in telophasis.
- Published
- 1998
19. Inhibition of tubulin polymerization in megakaryocyte cell lines leads to polyploidization which affects the metabolism of actin
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
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Cell Nucleus ,Polyploidy ,Cytoplasm ,Leukemia ,Ploidies ,Leukemia, Megakaryoblastic, Acute ,Tubulin ,Tumor Cells, Cultured ,Humans ,Colchicine ,Megakaryocytes ,Actins ,Cell Line - Abstract
Megakaryocyte polyploidization responds to platelet demand and results from the lack of cytoplasmic separation while the nucleus keeps dividing. In normal telophase, the plane of the actin constriction ring is determined by the tubulin spindle. In order to investigate the role of tubulin in the megakaryocyte polyploidization, two cell lines with megakaryocyte properties (DAMI and HEL) were incubated for 4 days in the presence or absence of colchicine (10 ng/ml), an inhibitor of the tubulin spindle. As compared to control conditions, cell cultured in the presence of colchicine reveal an augmentation of cell size, the apparition of multilobed nuclei and an increase in the cytoplasm basophilia, suggesting a megakaryocyte morphology. Furthermore, when cells are cultured in the presence of colchicine, diameters measured by morphometry augment from 17.4 microns +/- 1.7 to 34.5 microns +/- 2.0 and from 27.3 microns +/- 0.3 to 40.2 microns +/- 0.6 for DAMI and HEL cell lines, respectively (p0.05 by t-test). After four days of culture in the presence of colchicine, cells undergo arrest proliferation. Ploidy measured by flow cytometry, shows that control cells predominantly diploid (2N) become polyploid with the appearance of 8N, 16N and 32N cells after addition of colchicine. Moreover, the endomitotic index ¿mean of (log2 DNA content expressed in N)-l¿ increases significantly from 0.5 +/- 0.1 to 1.2 +/- 0.1 and from 0.6 +/- 0.1 to 1.4 +/- 0.0 after treatment with colchicine for the DAMI and HEL cell lines, respectively. To identify the nature of the molecules involved in this phenomenon, both forms of actin (monomeric, G- and polymerized, F-) were evaluated by a DNase I inhibition assay. G-actin contents in pg per 10(6) cells are 13.0 pg +/- 2.8 (m +/- SEM) and 1.0 pg +/- 0.1 for unstimulated DAMI and HEL cells. F-actin contents per 10(6) cells are 5.8 pg +/- 1.5 and 0.1 pg +/- 0.0 for DAMI and HEL cells. The addition of colchicine for four days of culture significantly increased the G-actin content (251% and 475% of controls) and F-actin content (170% and 619% of controls) for DAMI and HEL cell lines, respectively. In contrast, the G/F-actin ratio was not affected by colchicine. DAMI cells from each ploidy class were then sorted on an ELITE Coulter and assayed for actin content. While total actin, G-actin and F-actin per cell were augmented in polyploid cells cultured with colchicine, there was a reduction in G-, F- and total actin contents per diploid equivalent when cells become polyploid. In conclusion, these data suggest that inhibition of the tubulin spindle by colchicine induces polyploidization of megakaryocytes by a reduction of both forms of actin, possibly by preventing the actin constriction ring in the telophase.
- Published
- 1998
20. Inhibition of actin polymerization by cytochalasin B induces polyploidization and increases the number of nucleolar organizer regions in human megakaryocyte cell lines
- Author
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S, Baatout, B, Chatelain, P, Staquet, M, Symann, and C, Chatelain
- Subjects
Cell Nucleus ,Polyploidy ,Cytochalasin B ,Nucleolus Organizer Region ,Humans ,Megakaryocytes ,Actins ,Cell Division ,Cell Line - Abstract
Megakaryocyte polyploidization is an advantageous and regulated mechanism which leads to an increase in platelet production. In megakaryocyte cell lines, polyploidization can be obtained by using cytochalasin B, an inhibitor of the actin polymerization. The Nucleolar Organizer Regions (AgNORs) are parts of nucleolar DNA transcribed into ribosomal RNA. They are detected by silver staining technique and their number is proportional to protein synthesis. In order to estimate protein synthesis in polyploidizing megakaryocytes, AgNORs were measured in three cell lines with megakaryocyte properties (DAMI, HEL and K562) after a 4-day culture in the presence or absence of cytochalasin B, an inhibitor of the actin polymerization. The mean number of AgNORs per cell was 16.4 +/- 4.3 (m +/- SEM); 24.4 +/- 2.5 and 13.6 +/- 3.1 for DAMI, HEL and K-562 cell lines, respectively. The addition of cytochalasin B (2 micrograms/ml) increased significantly the number of AgNORs per cell (DAMI: 437%, HEL: 384% and K-562: 345% of controls, p0.05 by t-test). Moreover, the numbers of nucleoles per cell after addition of cytochalasin B were augmented significantly (DAMI: 258%, HEL: 271% and K-562: 264% of controls, p0.05 by t-test). The total protein content estimated by Bradford's method increased significantly to 938%, 326% and 388% of controls in DAMI, HEL and K562, respectively (p0.05 by t-test) in cells where actin was inhibited by cytochalasin B. In the presence of cytochalasin B, the endomitotic index (EI) [mean of (log2 DNA content expressed in N) 1] measured by flow cytometry increased to 368%, 207% and 538%, for DAMI, HEL and K-562 cell lines, respectively (p0.05 by t-test) after treatment with cytochalasin B. In contrast, the number of AgNORs per unit of DNA (EI) and the total protein content per unit of DNA did not change for DAMI, HEL and K-562 cell lines (p0.05 by t-test) after treatment with cytochalasin B. In conclusion, the increase in the number of the Nucleolar Organizer Regions by an agent known to stimulate polyploidization of megakaryocytic cell lines suggests that polyploidization occurs by enhanced protein production proportionally to DNA synthesis.
- Published
- 1998
21. Permeafix: a useful tool to detect antigens and DNA in flow cytometry
- Author
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S, Baatout and N, Cheţa
- Subjects
Fixatives ,Tissue Fixation ,Staining and Labeling ,Humans ,DNA ,Antigens ,Organic Chemicals ,Flow Cytometry - Abstract
A new product called Permeafix has been developed for gentle fixation of cells and permeability of their membranes. This product is useful for the staining of intracellular antigens and parallel quantification of DNA content simultaneously with cell surface staining.
- Published
- 1997
22. Interleukin-6 and megakaryocytopoiesis: an update
- Author
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S. Baatout
- Subjects
Blood Platelets ,medicine.medical_specialty ,medicine.medical_treatment ,Biology ,Internal medicine ,medicine ,Animals ,Humans ,Platelet ,Thrombopoiesis ,Interleukin 6 ,Cells, Cultured ,Megakaryocytopoiesis ,Inflammation ,Thrombocytosis ,Hematology ,Interleukin-6 ,Anemia ,General Medicine ,Hematopoietic Stem Cells ,Cell biology ,Hematopoiesis ,Haematopoiesis ,Cytokine ,Immunology ,biology.protein ,Hematopoietic progenitor cells ,Megakaryocytes - Abstract
Interleukin-6 is a pleiotropic cytokine which shows a wide variety of biologic functions on various tissues and cells. Indeed, IL-6 acts not only on B cells but also on T cells, hepatocytes, hematopoietic progenitor cells, megakaryocytes, etc. In this review, I have attempted to summarize the new data concerning the effect of IL-6 on megakaryocytes and platelets.
- Published
- 1996
23. Centrosome dynamics during the meiotic progression in the mouse oocyte
- Author
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S, Baatout, P, Jacquet, L, de Saint-Georges, and L, Baugnet-Mahieu
- Subjects
Centrosome ,Meiosis ,Mice ,Oocytes ,Animals - Published
- 1996
24. Matrigel: a useful tool to study endothelial differentiation
- Author
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S, Baatout and N, Cheţa
- Subjects
Molecular Sequence Data ,Neovascularization, Physiologic ,Cell Differentiation ,Basement Membrane ,Extracellular Matrix ,Drug Combinations ,Mice ,Animals ,Proteoglycans ,Amino Acid Sequence ,Collagen ,Endothelium, Vascular ,Laminin ,Cell Division - Abstract
Matrigel is a matrix of a mouse basement membrane neoplasm. It represents a complex mixture of basement membrane proteins including laminin, type IV collagen, entactin/nitrogen and proteoheparan sulfate, but it also contains growth factors. Matrigel induces endothelial cells to differentiate as evidenced by both the morphologic changes and by the reduction in proliferation and, therefore, offers a convenient model to study biochemical and molecular events associated with angiogenesis. Further, Matrigel permits to study the roles of the extracellular matrix in angiogenesis.
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- 1996
25. Molecular basis to understand polyploidy
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S Baatout
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Genetics ,Range (biology) ,media_common.quotation_subject ,Cell Cycle ,fungi ,food and beverages ,Hematology ,Plants ,Biology ,Evolution, Molecular ,Polyploidy ,Loss of heterozygosity ,Polyploid ,Evolutionary biology ,Neoplasms ,Genotype ,Plant species ,Animals ,Humans ,Reproduction ,Allele ,Ploidy ,media_common - Abstract
Polyploidy which is defined as an increase in chromosome number by an exact multiple of the haploid chromosome number is a typical characteristic of plant species but can also be found in almost all organisms from protists to humans. In the plant kingdom, since the reproduction can occur vegetatively, polyploid cells have time to settle down from the evolution point of view as a stable genetic system. So, 30 to 70% of angiosperms, including many important crop plants, are estimated to have polyploidy in their lineages. The success of polyploid species in plants has been attributed to their ability to colonise a wider range of habitats and to survive better in unstable climates compared with their diploid progenitors, presumably due to increased heterozygosity and flexibility provided by the presence of additional alleles.
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- 1999
26. Joint research towards a better radiation protection—highlights of the Fifth MELODI Workshop.
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A M Aerts, N R E N Impens, S Baatout, M A Benotmane, J Camps, J M Dabin, H Derradji, N Horemans, M Moreels, T Perko, R Quintens, L Struelens, F Hardeman, B Grosche, J-R Jourdain, J Repussard, W Rühm, and T Schneider
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RADIATION protection ,RADIATION doses ,FUKUSHIMA Nuclear Accident, Fukushima, Japan, 2011 ,RADIATION & the environment ,RADIATION damage ,CONFERENCES & conventions - Abstract
MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future. [ABSTRACT FROM AUTHOR]
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- 2014
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27. Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS).
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Radstake WE, Parisi A, Miranda S, Gautam K, Vermeesen R, Rehnberg E, Tabury K, Coppes R, van Goethem MJ, Brandenburg S, Weber U, Fournier C, Durante M, Baselet B, and Baatout S
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- Humans, Radiation, Ionizing, Cells, Cultured, DNA Damage, Fibroblasts radiation effects, Fibroblasts metabolism, DNA Breaks, Double-Stranded radiation effects, Hydrocortisone pharmacology, DNA Repair
- Abstract
Without the protective shielding of Earth's atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities., (© 2024. The Author(s).)
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- 2024
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28. How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?
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Willis CRG, Calvaruso M, Angeloni D, Baatout S, Benchoua A, Bereiter-Hahn J, Bottai D, Buchheim JI, Carnero-Diaz E, Castiglioni S, Cavalieri D, Ceccarelli G, Chouker A, Cialdai F, Ciofani G, Coppola G, Cusella G, Degl'Innocenti A, Desaphy JF, Frippiat JP, Gelinsky M, Genchi G, Grano M, Grimm D, Guignandon A, Herranz R, Hellweg C, Iorio CS, Karapantsios T, van Loon J, Lulli M, Maier J, Malda J, Mamaca E, Morbidelli L, Osterman A, Ovsianikov A, Pampaloni F, Pavezlorie E, Pereda-Campos V, Przybyla C, Rettberg P, Rizzo AM, Robson-Brown K, Rossi L, Russo G, Salvetti A, Risaliti C, Santucci D, Sperl M, Tabury K, Tavella S, Thielemann C, Willaert R, Monici M, and Szewczyk NJ
- Abstract
Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, "Biology in Space and Analogue Environments", focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: "How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?" The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed., (© 2024. The Author(s).)
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- 2024
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29. Radiation Doses Received by Major Organs at Risk in Children and Young Adolescents Treated for Cancer with External Beam Radiation Therapy: A Large-scale Study from 12 European Countries.
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Diallo I, Allodji RS, Veres C, Bolle S, Llanas D, Ezzouhri S, Zrafi W, Debiche G, Souchard V, Fauchery R, Haddy N, Journy N, Demoor-Goldschmidt C, Winter DL, Hjorth L, Wiebe T, Haupt R, Robert C, Kremer L, Bardi E, Sacerdote C, Terenziani M, Kuehni CE, Schindera C, Skinner R, Winther JF, Lähteenmäki P, Byrn J, Jakab Z, Cardis E, Pasqual E, Tapio S, Baatout S, Atkinson M, Benotmane MA, Sugden E, Zaletel LZ, Ronckers C, Reulen RC, Hawkins MM, and de Vathaire F
- Abstract
Purpose: Childhood cancer survivors, in particular those treated with radiation therapy, are at high risk of long-term iatrogenic events. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. We aimed to set up a standardized organ dose table to help former patients and clinicians in charge of long-term follow-up clinics., Methods and Materials: We performed whole body dosimetric reconstruction for 2646 patients from 12 European countries treated between 1941 and 2006 (median, 1976). Most plannings were 2- or 3-dimensional. A total of 46% of patients were treated using Cobalt 60, and 41%, using a linear accelerator. The median prescribed dose was 27.2 Gy (IQ1-IQ3, 17.6-40.0 Gy). A patient-specific voxel-based anthropomorphic phantom with more than 200 anatomic structures or substructures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the treatment planning system dose calculation to the whole body, by type and localization of childhood cancer., Results: The integral dose and normal tissue doses to most of the 23 considered organs increased between the 1950s and 1970s and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability., Conclusions: The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, sex, age, and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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30. How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?
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Davis T, Tabury K, Zhu S, Angeloni D, Baatout S, Benchoua A, Bereiter-Hahn J, Bottai D, Buchheim JI, Calvaruso M, Carnero-Diaz E, Castiglioni S, Cavalieri D, Ceccarelli G, Choukér A, Cialdai F, Ciofani G, Coppola G, Cusella G, Degl'Innocenti A, Desaphy JF, Frippiat JP, Gelinsky M, Genchi G, Grano M, Grimm D, Guignandon A, Hahn C, Hatton J, Herranz R, Hellweg CE, Iorio CS, Karapantsios T, van Loon JJWA, Lulli M, Maier J, Malda J, Mamaca E, Morbidelli L, van Ombergen A, Osterman A, Ovsianikov A, Pampaloni F, Pavezlorie E, Pereda-Campos V, Przybyla C, Puhl C, Rettberg P, Rizzo AM, Robson-Brown K, Rossi L, Russo G, Salvetti A, Santucci D, Sperl M, Tavella S, Thielemann C, Willaert R, Szewczyk N, and Monici M
- Abstract
Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed., (© 2024. The Author(s).)
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- 2024
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31. Monitoring functional immune responses with a cytokine release assay: ISS flight hardware design and experimental protocol for whole blood cultures executed under microgravity conditions.
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Buchheim JI, Feuerecker M, Balsamo M, Vukich M, Van Walleghem M, Tabury K, Quintens R, Vermeesen R, Baselet B, Baatout S, Rattenbacher B, Antunes I, Ngo-Anh TJ, Crucian B, and Choukér A
- Abstract
Introduction: Long-term space missions trigger a prolonged neuroendocrine stress response leading to immune system dysregulation evidenced by susceptibility to infections, viral reactivation, and skin irritations. However, due to existing technical constraints, real-time functional immune assessments are not currently available to crew inflight. The in vitro cytokine release assay (CRA) has been effectively employed to study the stimulated cytokine response of immune cells in whole blood albeit limited to pre- and post-flight sessions. A novel two-valve reaction tube (RT) has been developed to enable the execution of the CRA on the International Space Station (ISS). Methods: In a comprehensive test campaign, we assessed the suitability of three materials (silicone, C-Flex, and PVC) for the RT design in terms of biochemical compatibility, chemical stability, and final data quality analysis. Furthermore, we thoroughly examined additional quality criteria such as safety, handling, and the frozen storage of antigens within the RTs. The validation of the proposed crew procedure was conducted during a parabolic flight campaign. Results: The selected material and procedure proved to be both feasible and secure yielding consistent and dependable data outcomes. This new hardware allows for the stimulation of blood samples on board the ISS, with subsequent analysis still conducted on the ground. Discussion: The resultant data promises to offer a more accurate understanding of the stress-induced neuroendocrine modulation of immunity during space travel providing valuable insights for the scientific community. Furthermore, the versatile nature of the RT suggests its potential utility as a testing platform for various other assays or sample types., Competing Interests: MB is employed and MaV was employed by Kayser Italia S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Buchheim, Feuerecker, Balsamo, Vukich, Van Walleghem, Tabury, Quintens, Vermeesen, Baselet, Baatout, Rattenbacher, Antunes, Ngo-Anh, Crucian and Choukér.)
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- 2024
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32. In utero exposure to ionizing radiation and metabolic regulation: perspectives for future multi- and trans-generation effects studies.
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Grison S, Braga-Tanaka II, Baatout S, and Klokov D
- Abstract
Purpose: The radiation protection community has been particularly attentive to the risks of delayed effects on offspring from low dose or low dose-rate exposures to ionizing radiation. Despite this, the current epidemiologic studies and scientific data are still insufficient to provide the necessary evidence for improving risk assessment guidelines. This literature review aims to inform future studies on multigenerational and transgenerational effects. It primarily focuses on animal studies involving in utero exposure and discusses crucial elements for interpreting the results. These elements include in utero exposure scenarios relative to the developmental stages of the embryo/fetus, and the primary biological mechanisms responsible for transmitting heritable or hereditary effects to future generations. The review addresses several issues within the contexts of both multigenerational and transgenerational effects, with a focus on hereditary perspectives., Conclusions: Knowledge consolidation in the field of Developmental Origins of Health and Disease (DOHaD) has led us to propose a new study strategy. This strategy aims to address the transgenerational effects of in utero exposure to low dose and low dose-rate radiation. Within this concept, there is a possibility that disruption of epigenetic programming in embryonic and fetal cells may occur. This disruption could lead to metabolic dysfunction, which in turn may cause abnormal responses to future environmental challenges, consequently increasing disease risk. Lastly, we discuss methodological limitations in our studies. These limitations are related to cohort size, follow-up time, model radiosensitivity, and analytical techniques. We propose scientific and analytical strategies for future research in this field.
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- 2024
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33. Correction: Sallam et al. DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy. Int. J. Mol. Sci. 2022, 23 , 16214.
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Sallam M, Mysara M, Benotmane MA, Tamarat R, Santos SCR, Crijns APG, Spoor D, Van Nieuwerburgh F, Deforce D, Baatout S, Guns PJ, Aerts A, and Ramadan R
- Abstract
Radia Tamarat and Susana Constantino Rosa Santos were not included as authors in the original publication [...].
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- 2023
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34. Lost in Space? Unmasking the T Cell Reaction to Simulated Space Stressors.
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Miranda S, Vermeesen R, Radstake WE, Parisi A, Ivanova A, Baatout S, Tabury K, and Baselet B
- Subjects
- Humans, Interleukin-2, Hydrocortisone, Carbon, Space Flight, Weightlessness
- Abstract
The space environment will expose astronauts to stressors like ionizing radiation, altered gravity fields and elevated cortisol levels, which pose a health risk. Understanding how the interplay between these stressors changes T cells' response is important to better characterize space-related immune dysfunction. We have exposed stimulated Jurkat cells to simulated space stressors (1 Gy, carbon ions/1 Gy photons, 1 µM hydrocortisone (HC), Mars, moon, and microgravity) in a single or combined manner. Pro-inflammatory cytokine IL-2 was measured in the supernatant of Jurkat cells and at the mRNA level. Results show that alone, HC, Mars gravity and microgravity significantly decrease IL-2 presence in the supernatant. 1 Gy carbon ion irradiation showed a smaller impact on IL-2 levels than photon irradiation. Combining exposure to different simulated space stressors seems to have less immunosuppressive effects. Gene expression was less impacted at the time-point collected. These findings showcase a complex T cell response to different conditions and suggest the importance of elevated cortisol levels in the context of space flight, also highlighting the need to use simulated partial gravity technologies to better understand the immune system's response to the space environment.
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- 2023
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35. Adequacy of in-mission training to treat tibial shaft fractures in mars analogue testing.
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Manon J, Saint-Guillain M, Pletser V, Buckland DM, Vico L, Dobney W, Baatout S, Wain C, Jacobs J, Comein A, Drouet S, Meert J, Casla IS, Chamart C, Vanderdonckt J, Cartiaux O, and Cornu O
- Subjects
- Humans, Astronauts, Utah, Space Flight methods, Fractures, Bone, Mars
- Abstract
Long bone fractures are a concern in long-duration exploration missions (LDEM) where crew autonomy will exceed the current Low Earth Orbit paradigm. Current crew selection assumptions require extensive complete training and competency testing prior to flight for off-nominal situations. Analogue astronauts (n = 6) can be quickly trained to address a single fracture pattern and then competently perform the repair procedure. An easy-to-use external fixation (EZExFix) was employed to repair artificial tibial shaft fractures during an inhabited mission at the Mars Desert Research Station (Utah, USA). Bone repair safety zones were respected (23/24), participants achieved 79.2% repair success, and median completion time was 50.04 min. Just-in-time training in-mission was sufficient to become autonomous without pre-mission medical/surgical/mechanical education, regardless of learning conditions (p > 0.05). Similar techniques could be used in LDEM to increase astronauts' autonomy in traumatic injury treatment and lower skill competency requirements used in crew selection., (© 2023. Springer Nature Limited.)
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- 2023
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36. How do gravity alterations affect animal and human systems at a cellular/tissue level?
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Cialdai F, Brown AM, Baumann CW, Angeloni D, Baatout S, Benchoua A, Bereiter-Hahn J, Bottai D, Buchheim JI, Calvaruso M, Carnero-Diaz E, Castiglioni S, Cavalieri D, Ceccarelli G, Choukér A, Ciofani G, Coppola G, Cusella G, Degl'Innocenti A, Desaphy JF, Frippiat JP, Gelinsky M, Genchi G, Grano M, Grimm D, Guignandon A, Hahn C, Hatton J, Herranz R, Hellweg CE, Iorio CS, Karapantsios T, van Loon J, Lulli M, Maier J, Malda J, Mamaca E, Morbidelli L, van Ombergen A, Osterman A, Ovsianikov A, Pampaloni F, Pavezlorie E, Pereda-Campos V, Przybyla C, Puhl C, Rettberg P, Risaliti C, Rizzo AM, Robson-Brown K, Rossi L, Russo G, Salvetti A, Santucci D, Sperl M, Strollo F, Tabury K, Tavella S, Thielemann C, Willaert R, Szewczyk NJ, and Monici M
- Abstract
The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects., (© 2023. Springer Nature Limited.)
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- 2023
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37. DNA damage and repair: underlying mechanisms leading to microcephaly.
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Ribeiro JH, Altinisik N, Rajan N, Verslegers M, Baatout S, Gopalakrishnan J, and Quintens R
- Abstract
DNA-damaging agents and endogenous DNA damage constantly harm genome integrity. Under genotoxic stress conditions, the DNA damage response (DDR) machinery is crucial in repairing lesions and preventing mutations in the basic structure of the DNA. Different repair pathways are implicated in the resolution of such lesions. For instance, the non-homologous DNA end joining and homologous recombination pathways are central cellular mechanisms by which eukaryotic cells maintain genome integrity. However, defects in these pathways are often associated with neurological disorders, indicating the pivotal role of DDR in normal brain development. Moreover, the brain is the most sensitive organ affected by DNA-damaging agents compared to other tissues during the prenatal period. The accumulation of lesions is believed to induce cell death, reduce proliferation and premature differentiation of neural stem and progenitor cells, and reduce brain size (microcephaly). Microcephaly is mainly caused by genetic mutations, especially genes encoding proteins involved in centrosomes and DNA repair pathways. However, it can also be induced by exposure to ionizing radiation and intrauterine infections such as the Zika virus. This review explains mammalian cortical development and the major DNA repair pathways that may lead to microcephaly when impaired. Next, we discuss the mechanisms and possible exposures leading to DNA damage and p53 hyperactivation culminating in microcephaly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ribeiro, Altinisik, Rajan, Verslegers, Baatout, Gopalakrishnan and Quintens.)
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- 2023
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38. Bioprinting of Cardiac Tissue in Space: Where Are We?
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Tabury K, Rehnberg E, Baselet B, Baatout S, and Moroni L
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- Printing, Three-Dimensional, Tissue Engineering methods, Heart, Tissue Scaffolds, Bioprinting methods
- Abstract
Bioprinting in space is the next frontier in tissue engineering. In the absence of gravity, novel opportunities arise, as well as new challenges. The cardiovascular system needs particular attention in tissue engineering, not only to develop safe countermeasures for astronauts in future deep and long-term space missions, but also to bring solutions to organ transplantation shortage. In this perspective, the challenges encountered when using bioprinting techniques in space and current gaps that need to be overcome are discussed. The recent developments that have been made in the bioprinting of heart tissues in space and an outlook on potential future bioprinting opportunities in space are described., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
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- 2023
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39. Author Correction: The kidney, volume homeostasis and osmoregulation in space: current perspective and knowledge gaps.
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Olde Engberink RHG, van Oosten PJ, Weber T, Tabury K, Baatout S, Siew K, Walsh SB, Valenti G, Chouker A, Boutouyrie P, Heer M, Jordan J, and Goswami N
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- 2023
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40. A Dusty Road for Astronauts.
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Miranda S, Marchal S, Cumps L, Dierckx J, Krüger M, Grimm D, Baatout S, Tabury K, and Baselet B
- Abstract
The lunar dust problem was first formulated in 1969 with NASA's first successful mission to land a human being on the surface of the Moon. Subsequent Apollo missions failed to keep the dust at bay, so exposure to the dust was unavoidable. In 1972, Harrison Schmitt suffered a brief sneezing attack, red eyes, an itchy throat, and congested sinuses in response to lunar dust. Some additional Apollo astronauts also reported allergy-like symptoms after tracking dust into the lunar module. Immediately following the Apollo missions, research into the toxic effects of lunar dust on the respiratory system gained a lot of interest. Moreover, researchers believed other organ systems might be at risk, including the skin and cornea. Secondary effects could translocate to the cardiovascular system, the immune system, and the brain. With current intentions to return humans to the moon and establish a semi-permanent presence on or near the moon's surface, integrated, end-to-end dust mitigation strategies are needed to enable sustainable lunar presence and architecture. The characteristics and formation of Martian dust are different from lunar dust, but advances in the research of lunar dust toxicity, mitigation, and protection strategies can prove strategic for future operations on Mars.
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- 2023
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41. Next generation of astronauts or ESA astronaut 2.0 concept and spotlight on immunity.
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Jacob P, Oertlin C, Baselet B, Westerberg LS, Frippiat JP, and Baatout S
- Abstract
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 production
1,2 . 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., (© 2023. The Author(s).)- Published
- 2023
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42. Gravitational effects on fibroblasts' function in relation to wound healing.
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Radstake WE, Gautam K, Miranda S, Van Rompay C, Vermeesen R, Tabury K, Verslegers M, Dowson A, Gorissen J, van Loon JJWA, Savage NDL, Baatout S, and Baselet B
- Abstract
The spaceflight environment imposes risks for maintaining a healthy skin function as the observed delayed wound healing can contribute to increased risks of infection. To counteract delayed wound healing in space, a better understanding of the fibroblasts' reaction to altered gravity levels is needed. In this paper, we describe experiments that were carried out at the Large Diameter Centrifuge located in ESA-ESTEC as part of the ESA Academy 2021 Spin Your Thesis! Campaign. We exposed dermal fibroblasts to a set of altered gravity levels, including transitions between simulated microgravity and hypergravity. The addition of the stress hormone cortisol to the cell culture medium was done to account for possible interaction effects of gravity and cortisol exposure. Results show a main impact of cortisol on the secretion of pro-inflammatory cytokines as well as extracellular matrix proteins. Altered gravity mostly induced a delay in cellular migration and changes in mechanosensitive cell structures. Furthermore, 20 × g hypergravity transitions induced changes in nuclear morphology. These findings provide insights into the effect of gravity transitions on the fibroblasts' function related to wound healing, which may be useful for the development of countermeasures., (© 2023. The Author(s).)
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- 2023
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43. Myeloid cell infiltration in skeletal muscle after combined hindlimb unloading and radiation exposure in mice.
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Emanuelsson EB, Baselet B, Neefs M, Baatout S, Proesmans B, Daenen L, Sundberg CJ, Rundqvist H, and Fernandez-Gonzalo R
- Abstract
The skeletal muscle and the immune system are heavily affected by the space environment. The crosstalk between these organs, although established, is not fully understood. This study determined the nature of immune cell changes in the murine skeletal muscle following (hindlimb) unloading combined with an acute session of irradiation (HLUR). Our findings show that 14 days of HLUR induces a significant increase of myeloid immune cell infiltration in skeletal muscle., (© 2023. The Author(s).)
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- 2023
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44. Characterization of Non-Specific Uptake and Retention Mechanisms of [ 177 Lu]Lu-PSMA-617 in the Salivary Glands.
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Heynickx N, Segers C, Coolkens A, Baatout S, and Vermeulen K
- Abstract
The radionuclide therapy [
177 Lu]Lu-PSMA-617 was recently FDA-approved for treatment of metastatic castration-resistant prostate cancer. Salivary gland toxicity is currently considered as the main dose-limiting side effect. However, its uptake and retention mechanisms in the salivary glands remain elusive. Therefore, our aim was to elucidate the uptake patterns of [177 Lu]Lu-PSMA-617 in salivary gland tissue and cells by conducting cellular binding and autoradiography experiments. Briefly, A-253 and PC3-PIP cells, and mouse kidney and pig salivary gland tissue, were incubated with 5 nM [177 Lu]Lu-PSMA-617 to characterize its binding. Additionally, [177 Lu]Lu-PSMA-617 was co-incubated with monosodium glutamate, ionotropic or metabotropic glutamate receptor antagonists. Low, non-specific binding was observed in salivary gland cells and tissues. Monosodium glutamate was able to decrease [177 Lu]Lu-PSMA-617 in PC3-PIP cells, mouse kidney and pig salivary gland tissue. Kynurenic acid (ionotropic antagonist) decreased the binding of [177 Lu]Lu-PSMA-617 to 29.2 ± 20.6% and 63.4 ± 15.4%, respectively, with similar effects observed on tissues. (RS)-MCPG (metabotropic antagonist) was able to decrease the [177 Lu]Lu-PSMA-617 binding on A-253 cells to 68.2 ± 16.8% and pig salivary gland tissue to 53.1 ± 36.8%. To conclude, we showed that the non-specific binding on [177 Lu]Lu-PSMA-617 could be reduced by monosodium glutamate, kynurenic acid and (RS)-MCPG.- Published
- 2023
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45. The kidney, volume homeostasis and osmoregulation in space: current perspective and knowledge gaps.
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Olde Engberink RHG, van Oosten PJ, Weber T, Tabury K, Baatout S, Siew K, Walsh SB, Valenti G, Chouker A, Boutouyrie P, Heer M, Jordan J, and Goswami N
- Abstract
Although we have sent humans into space for more than 50 years crucial questions regarding kidney physiology, volume regulation and osmoregulation remain unanswered. The complex interactions between the renin-angiotensin-aldosterone system, the sympathetic nervous system, osmoregulatory responses, glomerular function, tubular function, and environmental factors such as sodium and water intake, motion sickness and ambient temperature make it difficult to establish the exact effect of microgravity and the subsequent fluid shifts and muscle mass loss on these parameters. Unfortunately, not all responses to actual microgravity can be reproduced with head-down tilt bed rest studies, which complicates research on Earth. Better understanding of the effects of microgravity on kidney function, volume regulation and osmoregulation are needed with the advent of long-term deep space missions and planetary surface explorations during which orthostatic intolerance complaints or kidney stone formation can be life-threatening for astronauts. Galactic cosmic radiation may be a new threat to kidney function. In this review, we summarise and highlight the current understandings of the effects of microgravity on kidney function, volume regulation and osmoregulation and discuss knowledge gaps that future studies should address., (© 2023. The Author(s).)
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- 2023
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46. Limnospira indica PCC 8005 Supplementation Prevents Pelvic Irradiation-Induced Dysbiosis but Not Acute Inflammation in Mice.
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Segers C, Mysara M, Coolkens A, Wouters S, Baatout S, Leys N, Lebeer S, Verslegers M, and Mastroleo F
- Abstract
Pelvic irradiation-induced mucositis secondarily leads to dysbiosis, which seriously affects patients' quality of life after treatment. No safe and effective radioprotector or mitigator has yet been approved for clinical therapy. Here, we investigated the potential protective effects of fresh biomass of Limnospira indica PCC 8005 against ionizing irradiation-induced mucositis and dysbiosis in respect to benchmark probiotic Lacticaseibacillus rhamnosus GG ATCC 53103. For this, mice were supplemented daily before and after 12 Gy X-irradiation of the pelvis. Upon sacrifice, food supplements' efficacy was assessed for intestinal barrier protection, immunomodulation and changes in the microbiota composition. While both could not confer barrier protection or significant immunomodulatory effects, 16S microbial profiling revealed that L. indica PCC 8005 and L. rhamnosus GG could prevent pelvic irradiation-induced dysbiosis. Altogether, our data show that-besides benchmarked L. rhamnosus GG- L. indica PCC 8005 is an interesting candidate to further explore as a radiomitigator counteracting pelvic irradiation-induced dysbiosis in the presented in vivo irradiation-gut-microbiota platform., Competing Interests: The authors declare no conflict of interest.
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- 2023
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47. Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?
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Harris KM, Arya R, Elias A, Weber T, Green DA, Greaves DK, Petersen LG, Roberts L, Kamine TH, Mazzolai L, Bergauer A, Kim DS, Olde Engberink RH, Zu Eulenberg P, Grassi B, Zuccarelli L, Baldassarre G, Tabury K, Baatout S, Jordan J, Blaber AP, Choukér A, Russomano T, and Goswami N
- Abstract
The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk., (© 2023. The Author(s).)
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- 2023
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48. Towards sustainable human space exploration-priorities for radiation research to quantify and mitigate radiation risks.
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Fogtman A, Baatout S, Baselet B, Berger T, Hellweg CE, Jiggens P, La Tessa C, Narici L, Nieminen P, Sabatier L, Santin G, Schneider U, Straube U, Tabury K, Tinganelli W, Walsh L, and Durante M
- Abstract
Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon's orbit, return to the Moon's surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit., (© 2023. The Author(s).)
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- 2023
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49. Comparison of in vitro scratch wound assay experimental procedures.
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Radstake WE, Gautam K, Van Rompay C, Vermeesen R, Tabury K, Verslegers M, Baatout S, and Baselet B
- Abstract
Fibroblast migration is an important aspect of wound healing. Different factors can influence migration and as such proper wound healing. In vitro scratch wound assays are used to examine cellular migration. However, the wide array of techniques available reduces reproducibility of findings. In this paper, we compare two techniques for wound creation; i.e. the exclusion method or scratching of cell monolayers. Furthermore, we investigate if analysis software influences experimental outcome by comparing both commercially and freely available analysis software. Besides, we examine the effect of cortisol on migration behavior of fibroblasts and identify possible caveats in experimental design. Results show a significantly reduced migration of fibroblasts when wounds are created using a cell exclusion method. Furthermore, addition of cortisol to the cell culture media only reduced migration of fibroblast monolayers that had been scratched but not in those where wounds were created using the exclusion method. A possible explanation related to cytokine expression is discussed., Competing Interests: The authors report no conflict of interest., (© 2023 The Authors.)
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- 2023
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50. The Effects of Combined Exposure to Simulated Microgravity, Ionizing Radiation, and Cortisol on the In Vitro Wound Healing Process.
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Radstake WE, Gautam K, Miranda S, Vermeesen R, Tabury K, Rehnberg E, Buset J, Janssen A, Leysen L, Neefs M, Verslegers M, Claesen J, van Goethem MJ, Weber U, Fournier C, Parisi A, Brandenburg S, Durante M, Baselet B, and Baatout S
- Subjects
- Humans, Hydrocortisone pharmacology, Weightlessness Simulation, Radiation, Ionizing, Wound Healing, Weightlessness adverse effects
- Abstract
Human spaceflight is associated with several health-related issues as a result of long-term exposure to microgravity, ionizing radiation, and higher levels of psychological stress. Frequent reported skin problems in space include rashes, itches, and a delayed wound healing. Access to space is restricted by financial and logistical issues; as a consequence, experimental sample sizes are often small, which limits the generalization of the results. Earth-based simulation models can be used to investigate cellular responses as a result of exposure to certain spaceflight stressors. Here, we describe the development of an in vitro model of the simulated spaceflight environment, which we used to investigate the combined effect of simulated microgravity using the random positioning machine (RPM), ionizing radiation, and stress hormones on the wound-healing capacity of human dermal fibroblasts. Fibroblasts were exposed to cortisol, after which they were irradiated with different radiation qualities (including X-rays, protons, carbon ions, and iron ions) followed by exposure to simulated microgravity using a random positioning machine (RPM). Data related to the inflammatory, proliferation, and remodeling phase of wound healing has been collected. Results show that spaceflight stressors can interfere with the wound healing process at any phase. Moreover, several interactions between the different spaceflight stressors were found. This highlights the complexity that needs to be taken into account when studying the effect of spaceflight stressors on certain biological processes and for the aim of countermeasures development.
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- 2023
- Full Text
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