1,721,015 research outputs found
Unravelling the effect of the interplay of spaceflight stressors on the in vitro wound healing process
No full textIn this work, an in vitro model of the simulated spaceflight environment was developed and applied to investigate the contribution of dermal fibroblasts in the wound healing process after exposure to simulated microgravity, ionizing radiation, and psychological stress. Besides, fibroblasts have been exposed to hypergravity and gravitational alterations between simulated microgravity and hypergravity, with or without stress hormones. After exposure to a combination of the aforementioned simulated spaceflight stressors, fibroblasts’ expression of cytokines and growth factors as well as dermal matrix proteins were measured. Additionally, measures of migration capacity and cytoskeletal remodeling were obtained as well. Finally, the effect of different radiation qualities on DNA damage and repair with or without the addition of stress hormones was investigated. The results show that the
wound healing capacity of dermal fibroblasts is sensitive for exposure to simulated spaceflight stressors. Moreover, it was shown that the different spaceflight stressors can interfere with the wound healing process at any stage. Additionally, several interaction effects between the different spaceflight stressors have been identified. Taken together, the insights of this work highlight the need of investigating the combined effect of simulated spaceflight stressors on the wound healing capacity of the skin
Immune system dysfunction in space : investigating the effects of the combined exposure to simulated space conditions on T cells
No full textThe space environment poses several health risks for astronauts and future space missions foresee extended periods of human presence in space (such as the creation of a permanent base on the Moon, or future missions to Mars). The immune system is one of the many systems affected by the space exposome.
This work describes the use of in vitro models for investigating the effects of simulated space conditions on T cell function, in order to elucidate their role in space-induced immune dysfunction.
Initially, a Jurkat cell line was used. Activated cells were exposed to ionizing radiation, stress hormone and simulated altered gravity conditions, namely microgravity, Moon gravity and Mars gravity. To understand how these space conditions affect T cell activation, the levels of IL-2 (important cytokine for T cell development and activity) were measured. Jurkat cell lines are good models for assessing T cell response however, since they are an immortalized cell line, the investigation of mechanistic responses is limited. For this, a second in vitro model, constituted of CD4+ T cells extracted from healthy volunteers, was used. These cells were exposed to ionizing radiation, simulated microgravity and stress hormones. A panel of cytokines as well as transcriptomics investigations were performed.
The results from both models showed a strong immunosuppression effect of simulated microgravity and stress hormone. Ionizing radiation exposure responses depended on the radiation quality, with different gene expression profiles being present. From the Jurkat cell model, partial gravity exposures showed different impacts of IL-2 levels, suggesting that the response may not be linear to the gravity level, thus future investigations are needed to better understand this modulation effects. CD4+ T cells results showed that simulated microgravity seems to favor Th2 profiles, shown at the cytokine secretion level, but also at the transcriptomic level. Moreover, while the exposure to ionizing radiation showed pro-inflammatory effects, the combination with the other simulated space conditions, particularly simulated microgravity, abrogated this effect, suggesting a complex interaction and alteration of the cells’ radiation response mechanisms.
Taken together, the insights from this doctoral work highlight the impact of the space environment on the immune system and provide a basis for future investigations.De ruimteomgeving brengt verschillende gezondheidsrisico's met zich mee voor astronauten, zeker met het oog op toekomstige ruimtemissies waarbij langere perioden van menselijke aanwezigheid in de ruimte worden voorzien (zoals het creëren van een permanente basis op de maan of toekomstige missies naar Mars). Het immuunsysteem is een van de vele systemen die beïnvloed worden door het ruimte-exposoom. Dit werk beschrijft het gebruik van in vitro modellen voor het onderzoek naar de effecten van gesimuleerde ruimteomstandigheden op de T-celfunctie, om zo hun rol in door de ruimte veroorzaakte immuundisfunctie op te helderen. In eerste instantie werd een Jurkat cellijn gebruikt. Geactiveerde cellen werden blootgesteld aan ioniserende straling, stresshormoon en gesimuleerde gewijzigde zwaartekrachtcondities, namelijk microzwaartekracht, maanzwaartekracht en Marszwaartekracht. Om te begrijpen hoe deze ruimtecondities de activering van T-cellen beïnvloeden, werden de niveaus van IL-2 (belangrijk cytokine voor de ontwikkeling en activiteit van T-cellen) gemeten. Jurkat cellijnen zijn goede modellen voor het beoordelen van de T cel respons, maar omdat het een geïmmortaliseerde cellijn is, is het onderzoek naar mechanistische responsen ermee eerder beperkt. Hiervoor werd een tweede in vitro model gebruikt, bestaande uit CD4 + T-cellen geëxtraheerd uit het bloed van gezonde vrijwilligers. Deze cellen werden blootgesteld aan ioniserende straling, gesimuleerde microzwaartekracht en stresshormoon. Er werd een panel van cytokinen en transcriptomics onderzoek uitgevoerd. De resultaten van beide modellen toonden een sterk immunosuppressie-effect van gesimuleerde microzwaartekracht en stresshormoon. De reacties op blootstelling aan ioniserende straling waren afhankelijk van de aard van de straling, gezien door de identificatie van verschillende genexpressieprofielen. Uit het Jurkat celmodel bleek dat de blootstelling aan gedeeltelijke zwaartekracht verschillende effecten had op IL-2 niveaus, wat suggereert dat de respons mogelijk niet evenredig is met het zwaartekrachtniveau. De resultaten van CD4+ T-cellen toonden aan dat gesimuleerde microzwaartekracht een Th2-profiel lijkt te bevorderen, wat blijkt uit het niveau van cytokinesecretie, maar ook uit het transcriptoom niveau. Bovendien, terwijl de blootstelling aan ioniserende straling pro-inflammatoire effecten vertoonde, ging de combinatie met de andere gesimuleerde ruimteomstandigheden, met name gesimuleerde microzwaartekracht, dit effect tegen, wat duidt op een complexe interactie en verandering van de stralingsresponsmechanismen van de cellen. Alles bij elkaar genomen benadrukken de verkregen inzichten van dit onderzoek de invloed van de ruimteomgeving op het immuunsysteem en bieden ze een basis voor toekomstig onderzoek
Molecular characterization of endothelial cell response in the context of radiation-induced atherosclerosis
No full textIonizing radiation is used for radiotherapeutic and diagnostic purposes, which can expose the heart and blood vessels, potentially causing cardiovascular diseases (CVDs). However, dose-dependency and associated molecular mechanisms are still elusive. Our work focused on endothelial cells based on previous information suggesting that ionizing radiation could promote atherosclerosis. We report that a single X-ray dose induces a time- and dose-dependent pro-atherosclerotic phenotype, linked with changes in cell cycle progression and induction of inflammation and senescence. By comparing responses to X-rays and Fe ion, radiation impact was found to be dependent on radiation quality, with a more pronounced and longer lasting response to Fe ions. Altogether, our data provide new molecular information on the causes of radiation-induced CVD and a basis on which to build new knowledge in order to ameliorate the current radiation protection system.Les radiations ionisantes sont utilisées à des fins diagnostiques et thérapeutiques, ce qui peut exposer le cœur et les vaisseaux sanguins, favorisant les maladies cardiovasculaires (CMVs). Or, la dépendance de dose et les mécanismes moléculaires de ces effets sont peu connus. Notre travail s’est intéressé aux cellules endothéliales sur base d’informations suggérant que les radiations ionisantes favorisent l’athérosclérose. Nous rapportons qu’une dose unique de rayons X induit un phénotype pro-arthérosclérotique dépendant du temps et de la dose, associé à des changements du cycle cellulaire et à l’induction d’inflammation et de sénescence. La comparaison des réponses aux rayons X et aux ions Fe montre que la qualité des rayons importe, avec des effets plus prononcés et plus longs pour les ions Fe. Nos résultats fournissent donc de nouvelles informations moléculaires relatives aux causes des CMVs radio-induites et une base de travail pour l’amélioration du système de radioprotection actuel.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201
The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
No full textDue to the advantages of charged particles compared to conventional radiotherapy, a vast increase is noted in the use of particle therapy in the clinic. These advantages include an improved dose deposition and increased biological effectiveness. Metastasis is still an important cause of mortality in cancer patients and evidence has shown that conventional radiotherapy can increase the formation of metastasizing cells. An important pathway involved in the process of metastasis is the Hedgehog (Hh) signaling pathway. Recent studies have demonstrated that activation of the Hh pathway, in response to X-rays, can lead to radioresistance and increased migratory, and invasive capabilities of cancer cells. Here, we investigated the effect of X-rays, protons, and carbon ions on cell survival, migration, and Hh pathway gene expression in prostate cancer (PC3) and medulloblastoma (DAOY) cell lines. In addition, the potential modulation of cell survival and migration by the Hh pathway inhibitor GANT61 was investigated. We found that in both cell lines, carbon ions were more effective in decreasing cell survival and migration as well as inducing more significant alterations in the Hh pathway genes compared to X-rays or protons. In addition, we show here for the first time that the Hh inhibitor GANT61 is able to sensitize DAOY medulloblastoma cells to particle radiation (proton and carbon ion) but not to conventional X-rays. This important finding demonstrates that the results of combination treatment strategies with X-ray radiotherapy cannot be automatically extrapolated to particle therapy and should be investigated separately. In conclusion, combining GANT61 with particle radiation could offer a benefit for specific cancer types with regard to cancer cell survival.sponsorship: KK is a recipient of a SCK.CEN-KUL PhD grant. KK, NB, MV, and BB received a Horizon2020 travel grant (No. 654002) for experiments at GANIL. KK received an EU CONCERT travel grant and Belgian Hadron therapy Consortium (BHTC) travel grant, whereas MM received an FWO travel grant to perform experiments at iThemba LABS in South-Africa. KH is a clinical research fellow of the Research Foundation Flanders, Belgium. (SCK.CEN-KUL PhD grant, Horizon2020 travel grant|654002, EU CONCERT travel grant, Belgian Hadron therapy Consortium (BHTC) travel grant, FWO travel grant)status: Publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Radiobiological risks following dentomaxillofacial imaging: should we be concerned?
Get PDFOBJECTIVES: This review aimed to present studies that prospectively investigated biological effects in patients following diagnostic dentomaxillofacial radiology (DMFR). METHODS: Literature was systematically searched to retrieve all studies assessing radiobiological effects of using X-ray imaging in the dentomaxillofacial area, with reference to radiobiological outcomes for other imaging modalities and fields. RESULTS: There is a lot of variability in the reported radiobiological assessment methods and radiation dose measures, making comparisons of radiobiological studies challenging. Most radiological DMFR studies are focusing on genotoxicity and cytotoxicity, data for 2D dentomaxillofacial radiographs, albeit with some methodological weakness biasing the results. For CBCT, available evidence is limited and few studies include comparative data on both adults and children. CONCLUSIONS: In the future, one will have to strive towards patient-specific measures by considering age, gender and other individual radiation sensitivity-related factors. Ultimately, future radioprotection strategies should build further on the concept of personalized medicine, with patient-specific optimization of the imaging protocol, based on radiobiological variables.sponsorship: This work was supported by the European Atomic Energy Community's Seventh Framework Programme FP7/2007-2011 under grant agreement No. 604984 (OPERRA: Open Project for the European Radiation Research Area) and by the Research Foundation - Flanders (FWO) under grant agreement No. G0A09.18N (TREASURE: Follow up of radiation dose and radiobiological effects after dental exposure to radiation). N. Belmans is supported by a doctoral SCK CEN grant. (European Atomic Energy Community|604984, Research Foundation - Flanders (FWO)|G0A09.18N, doctoral SCK CEN grant)status: Publishe
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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