7,469 research outputs found
Calcium signalling pathways in prostate cancer initiation and progression
No full textCancer cells proliferate, differentiate and migrate by repurposing physiological signalling mechanisms. In particular, altered calcium signalling is emerging as one of the most widespread adaptations in cancer cells. Remodelling of calcium signalling promotes the development of several malignancies, including prostate cancer. Gene expression data from in vitro, in vivo and bioinformatics studies using patient samples and xenografts have shown considerable changes in the expression of various components of the calcium signalling toolkit during the development of prostate cancer. Moreover, preclinical and clinical evidence suggests that altered calcium signalling is a crucial component of the molecular re-programming that drives prostate cancer progression. Evidence points to calcium signalling re-modelling, commonly involving crosstalk between calcium and other cellular signalling pathways, underpinning the onset and temporal progression of this disease. Discrete alterations in calcium signalling have been implicated in hormone-sensitive, castration-resistant and aggressive variant forms of prostate cancer. Hence, modulation of calcium signals and downstream effector molecules is a plausible therapeutic strategy for both early and late stages of prostate cancer. Based on this premise, clinical trials have been undertaken to establish the feasibility of targeting calcium signalling specifically for prostate cancer. [Abstract copyright: © 2023. Springer Nature Limited.
The cellular concentration of Bcl-2 determines its pro- or anti-apoptotic effect
No full textBcl-2 is an oncoprotein that is widely known to promote cell survival by inhibiting apoptosis. We explored the consequences of different expression paradigms on the cellular action of Bcl-2. Using either transient or stable transfection combined with doxycycline-inducible expression, we titrated the cellular concentration of Bcl-2. With each expression paradigm Bcl-2 was correctly targeted to the endoplasmic reticulum and mitochondria. However, with protocols that generated the greatest cellular concentrations of Bcl-2 the structure of these organelles was dramatically altered. The endoplasmic reticulum appeared to be substantially fragmented, whilst mitochondria coalesced into dense perinuclear structures. Under these conditions of high Bcl-2 expression, cells were not protected from pro-apoptotic stimuli. Rather Bcl-2 itself caused a significant amount of spontaneous cell death, and sensitised the cells to apoptotic agents such as staurosporine or ceramide. We observed a direct correlation between Bcl-2 concentration and spontaneous apoptosis. Expression of calbindin, a calcium buffering protein, or an enzyme that inhibited inositol 1,4,5-trisphosphate-mediated calcium release, significantly reduced cell death caused by Bcl-2 expression. We further observed that high levels of Bcl-2 expression caused lipid peroxidation and that the deleterious effects of Bcl-2 could be abrogated by the reactive oxygen species (ROS) scavenger Trolox. When stably expressed at low levels, Bcl-2 did not corrupt organelle structure or trigger spontaneous apoptosis. Rather, it protected cells from pro-apoptotic stimuli. These data reveal that high cellular concentrations of Bcl-2 lead to a calcium- and ROS-dependent induction of death. Selection of the appropriate expression paradigm is therefore crucial when investigating the biological role of Bcl-2. (C) 2007 Elsevier Ltd. All rights reserved
Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation.
No full textT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.We examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.In gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all p<0.05). By combining the three potential biomarkers, a TTCC signature was developed, which retained a significant association with OS both in stage IV and stage I-III patients. In lung and ovarian cancer, association with OS was also significant when all tumour stages were considered, but was partly lost or inconclusive after splitting cases into localized and metastatic subsets.Alterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation
D-SEED I.
No full textIt is an audiovisual film that presents a musical compilation of five artists accompanied by sculptural objects and is one of the other outputs of the ntity.one.Default platform. The ntity.one.Default platform has been a collectively curated platform connecting the independent electronic scene and visual art for two years. The audio-visual D-SEED I focuses on materiality, especially fabric, in sculptural objects. The haptic and tactile perception of art is the axis of interest in the artistic activity of the authors of these sculptural objects. Their creations outline a surreal world that is partly influenced by the reflection of the climate crisis we are facing. Michaela Rožnovská sculptural objects, in collaboration with Martin Dominik Kratochvíl, make imaginations of new animals on earth visible, based on abstracted shapes of plants or the simplest organisms living on this planet. They present themselves as heirs of our culture, mythology and religion. The sound side of the whole audiovisual film is created from a compilation of five performers - RLUNG, Thistle, Natálie Pleváková, sees_pod, timmi. The resulting sound mix is the work of the author sees_pod (Martin Dominik Kratochvíl). The whole compilation is composed of ambient surfaces, field recordings and processing. The whole is then built as a collage of constantly changing situations and emotions. At the moment when it may seem to the viewer that something identifiable emerges from the changing mixture, the composition turns into something else
D-SEED I.
No full textIt is an audiovisual film that presents a musical compilation of five artists accompanied by sculptural objects and is one of the other outputs of the ntity.one.Default platform. The ntity.one.Default platform has been a collectively curated platform connecting the independent electronic scene and visual art for two years. The audio-visual D-SEED I focuses on materiality, especially fabric, in sculptural objects. The haptic and tactile perception of art is the axis of interest in the artistic activity of the authors of these sculptural objects. Their creations outline a surreal world that is partly influenced by the reflection of the climate crisis we are facing. Michaela Rožnovská sculptural objects, in collaboration with Martin Dominik Kratochvíl, make imaginations of new animals on earth visible, based on abstracted shapes of plants or the simplest organisms living on this planet. They present themselves as heirs of our culture, mythology and religion. The sound side of the whole audiovisual film is created from a compilation of five performers - RLUNG, Thistle, Natálie Pleváková, sees_pod, timmi. The resulting sound mix is the work of the author sees_pod (Martin Dominik Kratochvíl). The whole compilation is composed of ambient surfaces, field recordings and processing. The whole is then built as a collage of constantly changing situations and emotions. At the moment when it may seem to the viewer that something identifiable emerges from the changing mixture, the composition turns into something else
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Příprava a charakterizace fosfolipidových biomembrán
No full textUniversita Karlova v Praze Přírodovědecká fakulta. Katedra biochemie Příprava a charakterizace fosfolipidových biomembrán Preparation and Characterization of Supported Phospholipid Biomembranes Souhrn disertační práce RNDr. Martin Beneš Školitelé: Doc. RNDr. Jiří Hudeček, CSc. Doc. Martin Hof, Dr. rer. nat. DSc. Prof. Wim Th.Hermens Praha 2008 2 3 Obsah Seznam publikací včleněných do disertační práce .........................................4 Úvod ...............................................................................................................5 Cíle disertační práce........................................................................................8 Výsledky..........................................................................................................9 Literatura .......................................................................................................14 Seznam publikací autora v časopisech..........................................................16 Prezentace na konferencích...........................................................................18 4 Seznam publikací včleněných do disertační práce I. Beneš, M., Billy, D., Hermens, W. and Hof, M.: Muscovite (mica) allows for the characterisation of supported bilayers by ellipsometry and confocal fluorescence...Charles University in Prague Faculty of Science, Department of Biochemistry Preparation and Characterisation of Supported Phospholipid Biomembranes Summary of PhD thesis RNDr. Martin Beneš Supervisors: Doc. RNDr. Jiří Hudeček, CSc. Doc. Martin Hof, Dr. rer. nat. DSc. Prof. Wim Th.Hermens Prague 2008 2 3 CONTENT List of publications included in the PhD thesis .............................. 4 Introduction ..................................................................................... 5 Objectives of the PhD thesis............................................................ 8 Results.............................................................................................. 9 References...................................................................................... 14 Publications of the author.............................................................. 16 Proceedings of scientific meetings and communications.............. 18 4 List of publications included in the PhD thesis I. Beneš, M., Billy, D., Hermens, W. and Hof, M.: Muscovite (mica) allows for the characterisation of supported bilayers by ellipsometry and confocal fluorescence correlation spectroscopy. Biol.Chem. 2002 383, 337-341. II. Benda, A., Beneš, M., Mareček, V., Lhotský, A., Hermens, W.T., and Hof. M.: How to determine diffusion...Katedra biochemieDepartment of BiochemistryFaculty of SciencePřírodovědecká fakult
Continuous Compliance scripts and data
No full textThis file contains the scripts and data used in the open-source portion (sections 6 and 7) of the paper "Continuous Compliance" by Martin Kellogg, Martin Schäf, Serdar Tasiran, and Michael D. Ernst, which appeared in Automated Software Engineering (ASE) 2020. Please contact the first author if you have any questions, concerns, or problems regarding this dataset - we would be happy to help you
Rent - seeking trade policy : a time series approach
No full textUsing a time-series approach, the author analyzes the relationship between the extent of rent-seeking trade policy and both political and economic variables. For rent-seeking trade policy, the indicator he uses is the number of foreign-trade regulations passed each year for the benefit of a single firm or industry. The author uses data from Uruguay for 1925-83. Uruguay, which experienced an impressive economic decline, is an outstanding example of a rent-seeking society. After being a wealthy economy in midcentury, it suffered almost complete stagnation, which led to social and policital disintegration by the end of the 1960s. Three decades of restrictive regulations on foreign trade had created a nearly closed economy by the end of the 1960s. It was worth analyzing whether policymakers'great receptiveness to demands for protection could account for Uruguay's decline. Over the period 1925-83, the author finds almost 4,000 laws, decrees, and administrative resolutions that create, maintain, or modify a foreign-trade regulation for the benefit of a single firm or industry. About half of them explicitly identify the petitioner - usually a firm or guild. Since the size of the Uruguayan economy changed over the period studied, the author scales the annual number of regulations by output or exports to measure the extent of rent-seeking trade policy. The author shows that the extent of rent-seeking trade policy increased with discretionary policies and under dictatorship. (In the period studied, there were two stages of democracy - until 1932 and from 1943-72 - and two stages of dictatorship.) He also shows that rent-seeking trade restrictions increased under import-substitution strategies and, more unexpectedly, under active export promotion. This suggests that discretionary power leads to wasteful distribution, whether it is used to support inward- or outward-oriented policies. Finally, the author analyzes the correlation between innovations in the trade policy indicator and innovations in the growth rates of output and exports, with a lag of up to 20 years. Surprisingly, he finds a positive correlation with output growth rates after two or three years. But the correlation becomes negative some years later, particularly in the case of exports. The short-run positive impact on growth rates, together with the surprisingly long time lag before the negative impact, may account for policymakers'receptiveness to demands for protection.Trade Policy,Achieving Shared Growth,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Economic Theory&Research,Environmental Economics&Policies
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