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Cadmium-induced stem cell proliferation: Schmidtea mediterranea's regenerative defence against carcinogenesis
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Cadmium-induced stem cell proliferation: Schmidtea mediterranea's regenerative defence against carcinogenesis
No full textnot availabl
Reference genes for qPCR assays in toxic metal and salinity stress in two flatworm model organisms
No full textThe flatworm species Schmidtea mediterranea
and Macrostomum lignano have become new and innovative model organisms in stem cell, regeneration and tissue
homeostasis research. Because of their unique stem cell
system, (lab) technical advantages and their phylogenetic
position within the Metazoa, they are also ideal candidate
model organisms for toxicity assays. As stress and biomarker screenings are often performed at the transcriptional level, the aim of this study was to establish a set of
reference genes for qPCR experiments for these two model
organisms in different stress situations. We examined the
transcriptional stability of nine potential reference genes
(actb, tubb, ck2, cox4, cys, rpl13, gapdh, gm2ap, plscr1) to
assess those that are most stable during altered stress
conditions (exposure to carcinogenic metals and salinity
stress). The gene expression stability was evaluated by
means of geNorm and NormFinder algorithms. Sets of best
reference genes in these analyses varied between different
stress situations, although gm2ap and actb were stably
transcribed during all tested combinations. In order to
demonstrate the impact of bad normalisation, the stressspecific gene hsp90 was normalised to different sets of
reference genes. In contrast to the normalisation according
to GeNorm and NormFinder, normalisation of hsp90 in
Macrostomum lignano during cadmium stress did not show
a significant difference when normalised to only gapdh. On
the other hand an increase of variability was noticed when
normalised to all nine tested reference genes together.
Testing appropriate reference genes is therefore strongly
advisable in every new experimental condition.This work was supported by PhD grants for Michelle Plusquin and Olivier DeGheselle from Hasselt University BOF (Bijzonder OnderzoeksFonds: BOF05N02 and BOF08G01) and Hasselt University tUL-impulsfinanciering, Andromeda Van Roten
was supported by Hasselt University tUL-impulsfinanciering (IMPF2PR). The authors gratefully acknowledge Dr. P. Ladurner (University of Innsbruck), Dr. M. Willems and S. Mouton (Ghent University) for providing us with cultures of the animals, and for their advice concerning maintenance of the cultures. They wish to thank Natascha Stefanie and Ria Vanderspikken for their skilful technical assistance. Dr. Nikki Watson (Australia) is greatly acknowledged for her critical reading of, and the linguistic comments on the manuscript
Redox-Related Mechanisms to Rebalance Cancer-Deregulated Cell Growth
No full textA delicate balance exists between the process of carcinogenesis and tissue regeneration. A number of malignant tumours are considered the outcome of an impaired or incomplete regeneration process, resulting in persistently dividing cells. Regeneration-competent tissues and animals are able to prevent and counteract growth abnormalities and seem to have a low vulnerability to chemical carcinogenesis. Cancer cell survival depends, among other things, on various redox-related mechanisms, which are targets of currently developed therapies. Disadvantages of these therapies are a lack of specificity and drug resistance. As the majority of these redox-related mechanisms also play an important role in successful and coordinated cell functioning and reproduction, the regeneration process offers a unique parallel context for modern cancer research. This review focuses on the interconnections between regeneration and carcinogenesis and how an understanding of regenerative forces and redox-controlled mechanisms could contribute to the identification of new therapeutic targets to block the growth and survival of cancer cells.</p
Planarians Customize Their Stem Cell Responses Following Genotoxic Stress as a Function of Exposure Time and Regenerative State
No full textAiming to in vivo characterize the responses of pluripotent stem cells and regenerative tissues to carcinogenic stress, we employed the highly regenerative organism Schmidtea mediterranea. Its broad regenerative capacities are attributable to a large pool of pluripotent stem cells, which are considered key players in the lower vulnerability toward chemically induced carcinogenesis observed in regenerative organisms. Schmidtea mediterranea is, therefore, an ideal model to study pluripotent stem cell responses with stem cells residing in their natural environment. Including microenvironmental alterations is important, as the surrounding niche influences the onset of oncogenic events. Both short-(3 days) and long-term (17 days) exposures to the genotoxic carcinogen methyl methanesulfonate (50 mu M) were evaluated during homeostasis and animal regeneration, two situations that render altered cellular niches. In both cases, MMS-induced DNA damage was observed, which provoked a decrease in proliferation on the short term. The outcome of DNA damage responses following long-term exposure differed between homeostatic and regenerating animals. During regeneration, DNA repair systems were more easily activated than in animals in homeostasis, where apoptosis was an important outcome. Knockdown experiments confirmed the importance of DNA repair systems during carcinogenic exposure in regenerating animals as knockdown of rad51 induced a stem cell-depleted phenotype, after regeneration was completed.Bijzonder OnderzoeksFonds of Hasselt University (grant number BOF08G01); Hasselt University tUL-impulsfinanciering (project toxicology) Fonds voor Wetenschappelijk Onderzoek (grant number 1522015N and PhD grant number R6411 to A.W.); Agentschap voor Innovatie door Wetenschap en Technologie (grant number 101442 to A.-S.S. and OZM grant number 100631 to M.W.)
A carcinogenic trigger to study the function of tumor suppressor genes in Schmidtea mediterranea
Full text linkPlanarians have been long known for their regenerative ability, which hinges on pluripotency. Recently, however, the planarian model has been successfully established for routine toxicological screens aimed to assess overproliferation, mutagenicity and tumorigenesis. In this study, we focused on planarian tumor suppressor genes (TSGs) and their role during chemically induced carcinogenic stress in Schmidtea mediterranea. Combining in silico and proteomic screens with exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs have a function in stem cells and that, in general, exposure to Cd accelerated the onset and increased the severity of the observed phenotype. This suggested that the interaction between environmental and genetic factors plays an important role in tumor development in S. mediterranea. Therefore, we further focused on the synergistic effects of Cd exposure and p53 knockdown (KD) at the cellular and molecular levels. Cd also produced a specific proteomic landscape in homeostatic animals, with 172 proteins differentially expressed, 43 of which were downregulated. Several of these proteins have tumor suppressor function in human and other animals, namely Wilms Tumor 1 Associated Protein (WT1), Heat Shock Protein 90 (HSP90), Glioma Pathogenesis-Related Protein 1 (GLIPR1) and Matrix Metalloproteinase B (Smed-MMPB). Both Glipr1 and MmpB KD produced large outgrowths, epidermal lesions and epidermal blisters. The epidermal blisters that formed as a consequence of Smed-MmpB KD were populated by smedwi1+ cells, many of which were actively proliferating, while large outgrowths contained ectopically differentiated structures, such as photoreceptors, nervous tissue and a small pharynx. In conclusion, Smed-MmpB is a planarian TSG that prevents stem cell proliferation and differentiation outside the proper milieu
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Full text linkWe 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
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