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Background Myocardin-related transcription factors (MRTF) A and B link actin dynamics and mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role in human mammary epithelial cells remains unclear. Methods Three-dimensional cultures of human mammary epithelial MCF10A cells were used to model acinar morphogenesis. Stable MRTF-A knockdown, MRTF-A/B rescue and MRTF-A/B overexpression was established to characterize the functional role during morphogenesis using confocal microscopy and expression analysis. Breast cancer patient databases were analyzed for MRTF-A expression. Results We showed that a precise temporal control of MRTFs is required for normal morphogenesis of MCF10A mammary acini. MRTF transcriptional activity, but not their protein amounts, is transiently induced during 3D acini formation. MRTF-A knockdown dramatically reduces acini size and prevents lumen formation. These effects are rescued by re-expression of MRTF-A, and partially by MRTF-B. Conversely, overexpression of MRTF-A and MRTF-B increases acini size, resulting in irregular spheroids without lumen and defective apico-basal polarity. These phenotypes correlate with deregulated expression of cell cycle inhibitors p21/Waf1, p27/Kip1 and altered phosphorylation of retinoblastoma protein. In MRTF overexpressing spheroids, proliferation and apoptosis are simultaneously increased at late stages, whilst neither occurs in control acini. MRTFs interfere with anoikis of the inner cells and cause an integrin switch from α6 to α5, repression of E-cadherin and induction of mesenchymal markers vimentin, Snai2 and Zeb1. Moreover, MRTF-overexpressing spheroids are insensitive to alteration in matrix stiffness. In two breast cancer cohorts, high expression of MRTF-A and known target genes was associated with decreased patient survival. Conclusion MRTF-A is required for proliferation and formation of mammary acini from luminal epithelial cells. Conversely, elevated MRTF activity results in pre-malignant spheroid formation due to defective proliferation, polarity loss and epithelial-mesenchymal transition.

A phoswich detector concept based on the combination of a high-Z element and a plastic element with a free running analogue-to-digital converter is presented in this work for the simultaneous measurement of operational dosimetric quantities H ∗ (10) and H ′ (0.07) in photon radiation fields. By means of a Pulse Shape Discrimination method and down to an energy of 60 keV ( 241 Am) in continuous photon radiation fields, the signal arriving at the common light sensor was separated into components coming from each element of the detector. In this context, crosstalk between the sensitive volumes represented an obstacle and was solved with a proper covering over one of the elements. Additionally, an algorithm for the calculation of the intended quantities based on the measured deposited doses was developed and tested using Monte Carlo methods with monoenergetic and X-ray radiation fields. Simulations set a validity region for the algorithm to the energy range between 20 keV and 3 MeV in the case of monoenergetic radiation and a lower energy cut of 15 keV in the case of X-ray fields. Furthermore, the algorithm was tested experimentally using 241 Am (60 keV) and 137 Cs (662 keV) sources against reference values from an OD-01 ionization chamber. Results showed a good sensitivity to the incoming photon energy, reflected in the variation of the ratio between the measured doses with the considered energies. At the same time, discrepancies between the measured and reference values of the operational quantities highlighted the need for a better calibration of the algorithm.

Activation studies are an important tool for nuclear decommissioning. By activating material samples in controlled conditions in a known neutron fluence rate, the expected activity in decommissioning can be estimated. This work focuses on determining the fluence rate of a moderated (α, n) neutron source, a key parameter for performing quantitative activity experiments. The fluence rate is determined by an absolute measurement of the accumulated activity of neutron-activated reference samples with a well-known composition using a βγ-coincidence setup. This method requires both single β- and γ- detection, as well as coincidence data. A main advantage of this technique is that the resulting measurement is mostly independent of individual detector efficiencies. The current setup uses a combination of two detectors, consisting of one γ- and one β-detector, paired with a multi-channel data acquisition system, simultaneously recording hits in the β- and γ-channels including their timestamps. Coincidences are extracted in the offline analysis from the stored data. Having singles and coincident data in one dataset reduces the impact of certain corrections, e.g. dead time. Additionally, Monte Carlo techniques were implemented to assess γ-interactions in the γ-detector and to account for the fraction of fake coincidences. Samples, including aluminum ( 27 Al), gold ( 197 Au), Vanadium ( 51 V), sodium chloride (NaCl), and manganese ( 55 Mn) were activated. Calculated thermal fluence rates from weakly attenuating samples agree within uncertainties, with an average fluence rate of Ψ 0 = (2.58 ± 0.09) × 10 5 cm -2 s -1 .

In vitro experiments with rat kidney cells exposed to 243 Am in cell culture medium show a decreasing cell viability with increasing americium concentration. Both the chemical cytotoxicity of americium and the dose caused by ionizing radiation have to be considered as possible causes. To determine the dose rate, a model which was reduced to the dosimetric relevant circumstances was set up. Since the size of the cells is in the micrometer range α -radiation makes the biggest contribution to the dose rate. Using the characteristic behaviour of α -particles the dose rate can be calculated from fluence and stopping power. Biological aspects like uptake of Americium into the cells as well as inaccuracies arising from inhomogeneity and dynamic behaviour in biological systems were taken into account. The dose rate was considered pointwise in the cell center and averaged over the whole cell. Calculations show that dose rates up to the Gy/h range were achieved at the highest americium concentrations of 8⋅10 -4 M. For an experimental comparison of the effect in dependence of the dose reference samples of untreated kidney cells were exposed to analog doses in an X-ray field. Taking relative biological effectiveness into account the cell viability curves depending on the dose show good agreement.

In vitro experiments with rat kidney cells exposed to 243Am in cell culture medium show a decreasing cell viability with increasing americium concentration. Both the chemical cytotoxicity of americium and the dose caused by ionizing radiation have to be considered as possible causes. To determine the dose rate, a model which was reduced to the dosimetric relevant circumstances was set up. Since the size of the cells is in the micrometer range α-radiation makes the biggest contribution to the dose rate. Using the characteristic behaviour of α-particles the dose rate can be calculated from fluence and stopping power. Biological aspects like uptake of Americium into the cells as well as inaccuracies arising from inhomogeneity and dynamic behaviour in biological systems were taken into account. The dose rate was considered pointwise in the cell center and averaged over the whole cell. Calculations show that dose rates up to the Gy/h range were achieved at the highest americium concentrations of 8⋅10-4 M. For an experimental comparison of the effect in dependence of the dose reference samples of untreated kidney cells were exposed to analog doses in an X-ray field. Taking relative biological effectiveness into account the cell viability curves depending on the dose show good agreement.

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader to the basic information about the field. We describe selected stem cell isolation techniques and stem cell markers for various stem cell populations. These include makers for endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin, Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1), mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section provides a concise summary of recent clinical trials involving stem cells directed towards improvement of a damaged myocardium. In the last part of the review, we reflect on the field and on future developments.

This article explores how some children in Denmark, Estonia, Germany and Sweden describe their perspective on learning. The aim of the international study is to gain knowledge of how preschool children in Sweden, Denmark, Estonia and Germany reflect and perceive their learning in preschool and other surrounding social contexts. The results are based on 51 focus group interviews from 181 children. The results indicate that, in general, children from all four countries seem to be aware of their own learning. One can conclude that encouraging children to think about what they are doing and why they are doing it makes the activities more goal-oriented from the children’s perspective and thus more conscious. Children are able to describe their own perspectives on learning.

This article explores how some children in Denmark, Estonia, Germany and Sweden describe their perspective on learning. The aim of theinternational study is to gain knowledge of how preschool children in Sweden, Denmark, Estonia and Germany reflect and perceive their learningin preschool and other surrounding social contexts. The results are based on 51 focus group interviews from 181 children. The results indicate that,in general, children from all four countries seem to be aware of their own learning. One can conclude that encouraging children to think about what they are doing and why they are doing it makes the activities more goal-oriented from the children’s perspective and thus more conscious. Children are able to describe their own perspectives on learning.

It is becoming increasingly evident that cancer constitutes a group of diseases involving altered stem-cell maturation/differentiation and the disturbance of regenerative processes. The observed malignant transformation is merely a symptom of normal differentiation processes gone astray rather than the primary event. This review focuses on the role of cancer stem cells (CSCs) in three common but also relatively under-investigated cancers: head and neck, ovarian, and testicular cancer. For didactic purpose, the physiology of stem cells is first introduced using hematopoietic and mesenchymal stem cells as examples. This is followed by a discussion of the (possible) role of CSCs in head and neck, ovarian, and testicular cancer. Aside from basic information about the pathophysiology of these cancers, current research results focused on the discovery of molecular markers specific to these cancers are also discussed. The last part of the review is largely dedicated to signaling pathways active within various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4, Wnt). Different elements of these pathways are also discussed in the context of therapeutic opportunities for the development of targeted therapies aimed at CSCs. Finally, alternative targeted anticancer therapies arising from recently identified molecules with cancer-(semi-)selective capabilities (e.g. apoptin, Brevinin-2R) are considered.