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Littérature scientifique sur le sujet « Screening, Signalling »

Auteur : Grafiati

Publié le 9 mars 2023

Mis à jour le 10 mars 2023

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Articles de revues sur le sujet "Screening, Signalling"

Jeong-Yoo Kim. « Signalling and Screening of Harsh Religious Norms ». Journal of Social Science 41, n^o 3 (décembre 2015) : 103–16. http://dx.doi.org/10.15820/khjss.2015.41.3.005.

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Wolff, Michael, Simone Krede, Dorothea Haasen, Jorg Wiedenmann, G. Nienhaus, Barbara Kistler, Franz Oswald et Ralf Heilker. « High Content Screening of CXCR2-Dependent Signalling Pathways ». Combinatorial Chemistry & ; High Throughput Screening 13, n^o 1 (1 janvier 2010) : 3–15. http://dx.doi.org/10.2174/138620710790218249.

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Chu, Wujin. « Demand Signalling and Screening in Channels of Distribution ». Marketing Science 11, n^o 4 (novembre 1992) : 327–47. http://dx.doi.org/10.1287/mksc.11.4.327.

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Antelo, Manel. « Screening and signalling for technology licensing : a comparison ». R&D Management 42, n^o 4 (27 août 2012) : 289–302. http://dx.doi.org/10.1111/j.1467-9310.2012.00684.x.

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Mori, Takayasu, Eriko Kikuchi, Yuko Watanabe, Shinya Fujii, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Eisei Sohara, Tatemitsu Rai, Sei Sasaki et Shinichi Uchida. « Chemical library screening for WNK signalling inhibitors using fluorescence correlation spectroscopy ». Biochemical Journal 455, n^o 3 (10 octobre 2013) : 339–45. http://dx.doi.org/10.1042/bj20130597.

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To discover WNK–OSR1/SPAK signalling inhibitors, we generated a new high-throughput system using fluorescent correlation spectroscopy capable of screening compounds that disrupt the binding of two molecules. We finally identified two novel and promising compounds for WNK–OSR1/SPAK signalling inhibition.

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Dosis, Anastasios. « On signalling and screening in markets with asymmetric information ». Journal of Mathematical Economics 75 (mars 2018) : 140–49. http://dx.doi.org/10.1016/j.jmateco.2018.01.001.

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Bassi, Vittorio, et Aisha Nansamba. « Screening and Signalling Non-Cognitive Skills : Experimental Evidence from Uganda ». Economic Journal 132, n^o 642 (1 octobre 2021) : 471–511. http://dx.doi.org/10.1093/ej/ueab071.

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Abstract We study how employers and job seekers respond to credible information on skills that are difficult to observe, and how this affects matching in the labour market. We experimentally vary whether certificates on workers’ non-cognitive skills are disclosed to both sides of the market during job interviews between young workers and small firms in Uganda. The certificates cause workers to increase their labour market expectations, while high-ability managers revise their assessments of the workers’ skills upwards. The reaction in terms of beliefs leads to an increase in positive assortative matching and to higher earnings for workers, conditional on employment.

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Fang, Qing, Fleurdeliz Maglangit, Linrui Wu, Rainer Ebel, Kwaku Kyeremeh, Jeanette H. Andersen, Frederick Annang, Guiomar Pérez-Moreno, Fernando Reyes et Hai Deng. « Signalling and Bioactive Metabolites from Streptomyces sp. RK44 ». Molecules 25, n^o 3 (22 janvier 2020) : 460. http://dx.doi.org/10.3390/molecules25030460.

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Streptomyces remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of Streptomyces sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) 1 together with five known compounds, cyclo-(L-Pro-Gly) 2, cyclo-(L-Pro-L-Phe) 3, cyclo-(L-Pro-L-Val) 4, cyclo-(L-Leu-Hyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC50 = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08 µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, 7–12 and six siderophores 13–18.

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Otero-Ramirez, Manuel E., Kyoko Matoba, Emiko Mihara, Toby Passioura, Junichi Takagi et Hiroaki Suga. « Macrocyclic peptides that inhibit Wnt signalling via interaction with Wnt3a ». RSC Chemical Biology 1, n^o 1 (2020) : 26–34. http://dx.doi.org/10.1039/d0cb00016g.

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Discovery and optimization of de novo macrocyclic peptide binders of Wnt3a through RaPID screening against an afamin-stabilized Wnt3a complex, capable of inhibiting Wnt signalling by direct interaction to the Wnt protein.

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Gründling, Angelika, et Vincent T. Lee. « Old concepts, new molecules and current approaches applied to the bacterial nucleotide signalling field ». Philosophical Transactions of the Royal Society B : Biological Sciences 371, n^o 1707 (5 novembre 2016) : 20150503. http://dx.doi.org/10.1098/rstb.2015.0503.

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Signalling nucleotides are key molecules that help bacteria to rapidly coordinate cellular pathways and adapt to changes in their environment. During the past 10 years, the nucleotide signalling field has seen much excitement, as several new signalling nucleotides have been discovered in both eukaryotic and bacterial cells. The fields have since advanced quickly, aided by the development of important tools such as the synthesis of modified nucleotides, which, combined with sensitive mass spectrometry methods, allowed for the rapid identification of specific receptor proteins along with other novel genome-wide screening methods. In this review, we describe the principle concepts of nucleotide signalling networks and summarize the recent work that led to the discovery of the novel signalling nucleotides. We also highlight current approaches applied to the research in the field as well as resources and methodological advances aiding in a rapid identification of nucleotide-specific receptor proteins. This article is part of the themed issue ‘The new bacteriology’.

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Thèses sur le sujet "Screening, Signalling"

MARCHESI, SILVIA. « Screening and Signalling in Debt Strategies : Theory and Empirics ». Doctoral thesis, University of Warwick, 2001. http://hdl.handle.net/10281/4658.

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This thesis focuses on public debt under asymmetry of information. The first part of the thesis deals with foreign debt while the second part with domestic debt. In the first part of this work (Chapter 1 and 2) a theoretical model is developed in which adoption of an IMF programme signals a country's productivity. It is assumed that there are two types of country, one with a high return on investment and the other with a low return. The country's type is known only to itself. In the presence of a debt overhang, the high productivity country may choose not to undertake the investment, despite it being socially efficient to do so. In this case the creditor would like to offer the country some debt reduction, but the low productivity type will also benefit from the debt reduction. This problem can be avoided if the country has sufficient resources to engage in a debt buyback in order to gain the debt relief: only the high productivity type would be prepared to sacrifice current resources for the debt reduction, and thus a separation of the two types is achieved. (This is similar to an argument found in Acharya and Diwan, 1993). We argue, however, that it is unlikely that a heavily indebted country will have sufficient resources for a buyback. If the country is credit constrained, an alternative screening mechanism is to undertake an IMF programme in return for debt reduction and possibly an IMF loan. This mechanism can be the equilibrium outcome even if the programme creates only disutility for the country's policy makers. The existence of an empirical relationship between the adoption of an IMF programme and the concession of a debt rescheduling by commercial and official creditors is tested in Chapter 3 using a bivariate probit model (to control for the endogeneity of the choice "IMF adoption"). If countries who have arrangements with the IMF are more likely than others to obtain a rescheduling of their external debt we could conclude that the adoption of an IMF programme could work as a sort of signal of a country's "good intent", which is thus rewarded with the debt relief. The results confirm the existence of a significant effect of the adoption of an IMF programme on the subsequent concession of a debt rescheduling by creditors. In the second part of the thesis we have investigated some of the consequences due to the existence of a large public debt (as it is the case in some of the European countries, e.g., Belgium, Greece, Ireland and Italy). More specifically, a theoretical model is developed, in Chapter 4, to examine whether buybacks of domestic debt may signal a government type. In the model it is assumed that the government could be of two types: a dry type and a wet type, according to its willingness to implement a fiscal stabilisation (in this model this basically means reducing fiscal spending). Asymmetry of information between the government and private investors is assumed. In particular interest rates are assumed to incorporate a risk premium which reflect the expectation that the inability to implement a stabilisation programme may result in more inflation and/or taxation, or debt default. In particular, during a fiscal stabilisation, private investors would lack confidence in the stabilisation programme and interest rates would be too high, reflecting this lack of credibility. Thus, a dry type who has to finance new spending may want to signal her resolution in order to lower the interest costs and one way to do that would be to repurchase a fraction of the outstanding debt. The wet type could also decide to buy-back some of his debt in order to pretend to be dry and to (possibly) lower his interest payments. It is showed that a critical amount of buyback exists such that the two types could be separated. Finally, in Chapter 5, evidence is provided in favour of the hypothesis that the repurchase of public debt is actually perceived as a good signal by private investors, consistently with the theoretical model. According to our results, the initial impact of the repurchase was to make the prices of the remaining bonds rise. This was consistent with our theory as we can interpret an increase in bonds price (and correspondingly a decrease in their rates of returns) as a signal that the buyback operation has positively affected the credibility of a government.

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Lin, Kuan Chee Bevan. « Using the RISCI genetic screening platform for elucidating apoptosis signalling network ». Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11662.

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Considerable development in the field of nanotechnology is increasingly yielding novel applications of nanoparticles. The unique properties of nanoparticles in particular their high aspect ratio (length : width ratio), however could pose potential risks to the user. A high throughput genetic screening platform, RISCI (robotic single cDNA investigation), was previously established for the systematic evaluation of single gene activities. Here, RISCI was utilised to identify pro-apoptotic genes as well as genes involved in the positive and negative regulation of silica nanoparticle-induced cell death. This project describes the further development of the screening platform by harnessing its capability to screen a cDNA library comprising approximately 30,000 full length, completely annotated, and sequenced human genes for novel regulators of apoptosis. It integrates an extensive skill sets and is broadly organised into three major phases: Setup, Screen and Analysis. The integration of a pro-apoptosis treatment to screen for inhibitors and sensitizers is a novel aspect of the current experimental setup, along with the low redundancy library. The extensive setup phase focused on technical aspects. The cDNA library, acquired as plasmid DNA, was transformed into a bacterial host for replication and subsequent DNA isolation. A new high-throughput process was developed encompassing the production of competent bacteria and a heat shock transformation protocol, which was subsequently transferred onto the robotic platform. In parallel, the software controlling the robots was redeveloped to allow for execution of user-defined protocols while novel transfection protocols were adapted for automation. The screen identified 699 apoptosis inducers, 1,141 inhibitors and 626 sensitizers. Bioinformatics analysis revealed that the inducers were highly enriched for cell death associated terms, while the inhibitors were strongly associated with cancer profiles. Both inducers and sensitizers were predominantly achieving the functional effect on the protein level, but inhibitors were mainly transcription based. Enriched metal response genes also suggest that the silica nanoparticles were causing their toxicity through reactive oxygen species generation. Intriguingly, the screen identified many noncoding sequences as being functionally capable of regulating apoptosis. These noncoding candidates are capable of regulating the protein coding counterparts identified from the screen. The truly interesting part of the project outcome remains those unknown candidates that were implicated in apoptosis regulation for the first time. Dissemination of the consolidated candidate list would help accelerate the experimental validation of these candidates and aid other researchers in deriving novel hypotheses when the candidates are placed in their research context. [For supplementary files please contact author].

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Lloyd-Lewis, Bethan. « High-throughput screening for novel regulators of Beta-catenin in Wnt signalling ». Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/24229/.

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Beta-catenin is a crucial component of the Wnt signalling pathway, which is imperative in many developmental processes and aberrantly regulated in several different cancers. The standard model of Wnt/Beta-catenin signalling states that, upon stimulation by Wnt ligand, Beta-catenin accumulates and subsequently translocates to the nucleus to activate TCF-dependent transcription of a variety of target genes, including oncogenes. However, the mechanisms regulating the nuclear localisation of Beta-catenin and its correlation with TCF-dependent transcription are poorly understood. In order to identify novel regulators of Beta-catenin levels and localisation in Wnt signalling imaging-based high-throughput knockout screens were developed in a Wnt inducible cell line, in addition to a cancer cell line in the presence of normal and downregulated APC. Results from the screens show that, in addition to known Wnt signalling components, genes not previously ascribed to the pathway appeared to modulate Beta-catenin. The study has provided sources of possible mechanistic insights into a number of areas of biology that may be involved in β-catenin regulation. Furthermore, it reveals an unprecedented degree of cross talk between Wnt and many other major signalling pathways. Moreover, the data indicated a degree of cell-type specificity in the regulators identified and, significantly, a lack of correlation between β-catenin levels and transcriptional activity.

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Bielig, Harald Frank Verfasser], Jonathan [Akademischer Betreuer] Howard et Mats [Akademischer Betreuer] [Paulsson. « Screening for components involved in NLR-mediated immune signalling / Harald Frank Bielig. Gutachter : Jonathan Howard ; Mats Paulsson ». Köln : Universitäts- und Stadtbibliothek Köln, 2012. http://d-nb.info/1038226805/34.

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Rudge, Felicity. « Genome-wide cDNA and RNAi screening to identify modulators of responses to a novel Wnt signalling inhibitor ». Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/58589/.

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Wnt/β-catenin signalling plays a central role in the regulation of multicelluar organism development and in the maintenance of tissue homeostasis in adults. Dysregulation of Wnt signalling resulting in aberrant pathway activation is a key initiating step in the development of a diverse range of cancers, including colorectal cancer, and as such is an important target for therapeutic intervention. A novel Wnt pathway inhibitor, ‘MSC’, has been identified as blocking activated Wnt signalling, specifically through inhibiting the ability of CDK8 and CDK19 to activate nuclear β-catenin/TCF-dependent transcription. However, despite potently inhibiting Wnt-dependent transcription, the ability of MSC to reduce cellular viability was limited. This study aimed to determine genes that whose loss operated with MSC to reduce cell survival. A whole-genome RNAi chemical sensitisation screen identified 3 genes whose depletion in combination with MSC treatment conditionally reduced the viability of HCT116 cells in vitro. The outstanding hit of this screen was Histidyl Aminoacyl tRNA Synthetase (HARS). The identification of this enzyme as an MSC ‘interactor’ suggested links between Wnt signalling and the regulation of translation. BRAF and MED11 RNAi also conferred conditional sensitivity to MSC. Interestingly, MED11 is a component of the Mediator complex, a multiprotein transcription regulatory complex in which CDK8 functions to regulate β-catenin/TCF-dependent transcription, suggesting that mediator complex may be a key target of MSC action. A parallel overexpression screen was initiated to identify novel Wnt pathway activators, and subsequently used to map MSC resistance. Expression of the transcription factors GBX1 and HMGB2, determined to be novel regulators of TCF-dependent transcription, blocked MSC-mediated disruption of Wnt signalling. Overexpression of either gene in a clinical context might therefore be regarded as a contra-indication for MSC-class therapies. These studies have highlighted potential avenues for broadening the scope of MSC activity through the determination of survival and resistance mechanisms, thus the rational design of MSC-combination therapies could be of huge clinical benefit for the treatment of colorectal cancer.

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Bielig, Harald Frank [Verfasser], Jonathan Akademischer Betreuer] Howard et Mats [Akademischer Betreuer] [Paulsson. « Screening for components involved in NLR-mediated immune signalling / Harald Frank Bielig. Gutachter : Jonathan Howard ; Mats Paulsson ». Köln : Universitäts- und Stadtbibliothek Köln, 2012. http://d-nb.info/1038226805/34.

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Matsuo, Koji. « Significance of dopamine D1 receptor signalling for steroidogenic differentiation of human induced pluripotent stem cells ». Kyoto University, 2018. http://hdl.handle.net/2433/232124.

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Lago, Cooke Santiago Guillermo. « A novel pipeline for drug discovery in neuropsychiatric disorders using high-content single-cell screening of signalling network responses ex vivo ». Thesis, University of Cambridge, 2016. https://www.repository.cam.ac.uk/handle/1810/270297.

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The current work entails the development of a novel high content platform for the measurement of kinetic ligand responses across cell signalling networks at the single-cell level in distinct PBMC subtypes ex vivo. Using automated sample preparation, fluorescent cellular barcoding and flow cytometry the platform is capable of detecting 21, 840 parallel cell signalling responses in each PBMC sample. We apply this platform to characterize the effects of neuropsychiatric treatments and CNS ligands on the T cell signalling repertoire. We apply it to define cell signalling network abnormalities in PBMCs from drug-naïve first-onset schizophrenia patients (n=12) relative to healthy controls (n=12) which are subsequently normalized in PBMCs from the same patients (n=10) after a six week course of clinical treatment with the atypical antipsychotic olanzapine. We then validate the abnormal cell signalling responses in PBMCs from an independent cohort of drug-naïve first-onset schizophrenia patients (n=25) relative to controls (n=25) and investigate the specificity of the abnormal PBMC responses in schizophrenia as compared to major depression (n=25), bipolar disorder (n=25) and autism spectrum disorder (n=25). Subsequently we conduct a phenotypic drug screen using the US Food and Drug Administration (FDA) approved compound library, in addition to experimental neuropsychiatric drug candidates and nutraceuticals, to identify compounds which selectively normalize the schizophrenia-associated cell signalling response. Finally these candidate compounds are characterized using structure-activity relationships to reveal specific chemical moieties implicated in the putative therapeutic effect.

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Whalen, Daniel M. « Structural and functional studies of the hedgehog signalling pathway ». Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:ce0e765c-04f1-4a64-a67b-89204ecaa155.

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Hedgehog (Hh) morphogens play fundamental roles in development whilst dysregulation of Hh signalling leads to disease. Multiple receptors are involved in the modulation of Hh morphogens at the cell surface. Among these, the interactions of Hh ligands with glycosaminoglycan (GAG) (for example heparan or chondroitin sulphate) chains of proteoglycans in the extracellular matrix play a key role in shaping morphogen gradients and fulfil important functions in signal transduction. Several high resolution crystal structures of Sonic Hh (Shh)-GAG complexes have been determined. The interaction determinants, confirmed by binding studies and mutagenesis reveal a novel Hh site for GAG interactions, which appears to be common to all Hh proteins. This novel site is supported by a wealth of published functional data, and resides in a hot spot region previously found to be crucial for Hh receptor binding. Crystal packing analysis combined with analytical ultracentrifugation on Hh-GAG complexes suggest a potential mechanism for GAG-dependent multimerisation. A key step in the Hh pathway is the transduction of the Hh signal into the receiving cell. The Hh signal transducer, Smoothened, is a key target drug target in the pathway with several modulators in clinical trials, despite an absence of structural data. Smoothened is required to activate all levels of Hh signalling. Recent evidence points to the conserved N-terminal ectodomain (ECD) in regulating Smo activity, from vertebrates to invertebrates. Despite the central importance of the ECD, its precise function remains elusive. A crystal structure of the ECD at 2.2 Å resolution is reported here. Structural analysis and biophysical experiments are discussed with reference to the potential function of this intriguing domain.

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ALFRED, VICTOR IFEOLUWA. « GENETIC SCREENING TO IDENTIFY INTERACTORS OF ESCRT-II SUBUNIT, VPS25, AND PRELIMINARY CHARACTERISATION OF CANDIDATES ». Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/560382.

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ESCRT (Endosomal Sorting Complex Required for Transport) proteins regulate cell surface receptor degradation by sorting and packaging ubiquitinated cargoes into the intraluminal vesicles of multivesicular bodies (MVBs). A range of human diseases including cancer, and neurodegeneration display altered expression or are caused by mutations of ESCRT subunits. Studies have shown that Drosophila tissues lacking ESCRTs display neoplastic-like features like overproliferation and polarity defects, partly due to aberrant signalling including Notch signalling. To understand ESCRT-regulated processes in vivo, we utilised modification of a deformed wing phenotype specifically caused by knockdown (RNAi) of Vps25, an ESCRT-II subunit. We systematically screened chromosomal regions and identified 204 genetic interactors of Vps25 that enhanced/suppressed the phenotype. They include genes that function in trafficking, signalling, transcription, ion transport and many other biological processes; suggesting that ESCRTs influence a wide range of biological processes. We have focused on a subset of these hits that regulate tissue growth with a secondary screen based on modification of a Delta-driven eye overgrowth phenotype, isolating a subset of 43 genes involved in regulating tissue growth, some of which are novel and uncharacterised. Human orthologues of some of these genes are important in cancers; dropout (dop), whose mammalian orthologues are the MAST kinases, have been shown to contribute towards breast cancer development. dop mediates Delta-driven eye overgrowth possibly by upregulating Delta expression. In human cells, MAST2 does not affect Notch signalling but might contribute to tumorigenesis by regulating the NFκB pathway. We have also characterised another interactor, CG12163 which is the homologue of mammalian Cathepsin F. Mutations in Cathepsin F cause a rare form of neuronal ceroid lipofuscinosis (NCL) called Type B Kufs disease. Our Drosophila model which recapitulates aspects of the human disease phenotype suggests that defects in autophagy might underlie the pathogenesis of NCLs.

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Livres sur le sujet "Screening, Signalling"

Dolton, Peter J. Signalling and screening in the graduate labour market. Hull : University of Hull, 1986.

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Dolton, Peter J. Signalling and screening in the graduate labour market. Hull : University of Hull. Dept of Economics and Commerce, 1985.

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Chapitres de livres sur le sujet "Screening, Signalling"

Hörner, Johannes. « Signalling and Screening ». Dans The New Palgrave Dictionary of Economics, 1–7. London : Palgrave Macmillan UK, 2008. http://dx.doi.org/10.1057/978-1-349-95121-5_2097-1.

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Hörner, Johannes. « Signalling and Screening ». Dans The New Palgrave Dictionary of Economics, 12314–21. London : Palgrave Macmillan UK, 2018. http://dx.doi.org/10.1057/978-1-349-95189-5_2097.

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Kaestner, Lars. « A system for optical high resolution screening of electrical excitable cells ». Dans Calcium signalling, 45–58. Berlin, Heidelberg : Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-34617-0_13.

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Feno, Simona, Giulia Di Marco, Agnese De Mario, Halenya Monticelli et Denis Vecellio Reane. « High-Throughput Screening Using Photoluminescence Probe to Measure Intracellular Calcium Levels ». Dans Calcium Signalling, 1–14. New York, NY : Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9018-4_1.

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Hucke, Anja. « Screening und Signalling als vorvertragliche Auswahlmechanismen ». Dans Gesellschafter und Geschäftsführer der GmbH, 37–48. Wiesbaden : Deutscher Universitätsverlag, 1996. http://dx.doi.org/10.1007/978-3-663-08520-1_3.

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Bollati-Fogolín, M., M. Oggero, S. Mirazo, R. Frank, R. Kratje et W. Müller. « Screening of Natural Compounds Affecting Type I Interferon Signalling ». Dans Cells and Culture, 485–87. Dordrecht : Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-3419-9_86.

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Joll, Caroline, Chris Mckenna, Robert Mcnabb et John Shorey. « Uncertainty, screening and signalling ». Dans Developments in Labour Market Analysis, 73–98. Routledge, 2018. http://dx.doi.org/10.4324/9780429025204-5.

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Chew, Shern L. « Molecular aspects of hormonal regulation ». Dans Oxford Textbook of Endocrinology and Diabetes, 29–33. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.1024.

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The wide molecular effects of hormones have complicated the understanding of how hormones work on a cell. The old view was of a linear signalling pathway from the receptor to the nucleus, thereby stimulating gene transcription. This view is probably an oversimplification. Hormones can not only regulate most of the molecular machines of the cell, certainly the transcription machinery, but also others. These machines perform and coordinate functions such as RNA and protein biosynthesis, macromolecular transport, cell division or death, and intracellular signalling. Physiological studies have shown that hormonal regulation is specific, yet flexible, and has the ability to generate feedback loops. Advances in genetics, cellular, and molecular biology, and biochemistry have allowed much new, and sometimes confusing, data on the mechanisms underlying hormonal regulation. Many advances have been due to methods of identifying and verifying networks of interactions between proteins. One example is the yeast two-hybrid system, an in vivo genetic screening method for such interactions. Another example is the use of protein tagging (e.g. with histidine residues) which can allow rapid and high-yield protein purification for biochemical studies. This chapter will briefly review some of the mechanisms of hormonal regulation.

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Eisen, Tim, Freddie C. Hamdy et Robert A. Huddart. « Malignant diseases of the urinary tract ». Dans Oxford Textbook of Medicine, sous la direction de John D. Firth, 5136–49. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0508.

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Bladder cancer—the seventh commonest cancer in the United Kingdom and the fourth most common in men. Nonmuscle-invasive disease is usually treated by transurethral resection with postoperative intravesical chemotherapy with mitomycin or bacillus Calmette–Guérin. Local muscle-invasive disease in patients who are fit enough is usually treated with radical cystoprostatectomy and cisplatin-based chemotherapy. Metastatic disease is typically treated with cisplatin-based chemotherapy. Renal cell cancer—approximately 3% of the total cancer burden. For operable patients with no distant disease, the treatment of choice is nephron-sparing (if possible) or radical nephrectomy. Metastatic renal cancer can behave in a very variable manner. Palliative nephrectomy may be required for bleeding or pain. First-line systemic treatment is with antiangiogenic tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor signalling. Prostate cancer—second most common cause of male cancer deaths in the Western world. Most cases are asymptomatic at presentation, being detected following measurement of serum prostate-specific antigen (PSA) or after digital rectal examination, although screening by measurement of PSA remains a contentious issue. Clinically localized prostate cancer is treated with active monitoring, radiotherapy, or minimally invasive surgery. Locally advanced disease is likely to progress and requires intervention, usually in the form of androgen deprivation therapy and radiotherapy. First-line treatment for metastatic prostate cancer is androgen deprivation therapy; second-line treatment may be with newer antiandrogens in combination with steroids and cytotoxics. Testicular cancer—affects predominantly young adult men in whom they are the most common malignant tumours. For most patients, initial management consists of an inguinal orchidectomy, with or without immediate adjuvant therapy. Standard treatment of metastatic germ cell tumours is with a combination of bleomycin, etoposide, and cisplatin.

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Actes de conférences sur le sujet "Screening, Signalling"

« Screening and Signalling in a Contractual Savings for Housing System : The German Bausparkassen System ». Dans 9th European Real Estate Society Conference : ERES Conference 2002. ERES, 2002. http://dx.doi.org/10.15396/eres2002_221.

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Takayama, Shuichi, Yi-Chung Tung et Bor-Han Chueh. « Biological Micro/Nanofluidics ». Dans ASME 2008 First International Conference on Micro/Nanoscale Heat Transfer. ASMEDC, 2008. http://dx.doi.org/10.1115/mnht2008-52087.

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Many biological studies, drug screening methods, and cellular therapies require culture and manipulation of living cells outside of their natural environment in the body. The gap between the cellular microenvironment in vivo and in vitro, however, poses challenges for obtaining physiologically relevant responses from cells used in basic biological studies or drug screens and for drawing out the maximum functional potential from cells used therapeutically. One of the reasons for this gap is because the fluidic environment of mammalian cells in vivo is microscale and dynamic whereas typical in vitro cultures are macroscopic and static. This presentation will give an overview of efforts in our laboratory to develop programmable microfluidic systems that enable spatio-temporal control of both the chemical and fluid mechanical environment of cells. The technologies and methods close the physiology gap to provide biological information otherwise unobtainable and to enhance cellular performance in therapeutic applications. Specific biomedical topics that will be discussed include subcellular signalling in normal and cancer cells, in vitro fertilization on a chip, studies of the effect of physiological and pathological fluid mechanical stresses on endothelial and epithelial cells, and microfluidic stem cell engineering. In the nanoscale regime, tunable nanochannels that can manipulate single DNA molecules will be discussed.

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Dutta Roy, T., J. J. Stone, W. Sun, E. H. Cho, S. J. Lockett, F. W. Wang et L. Henderson. « Osteoblast Adhesion on Tissue Engineering Scaffolds Made by Bio-Manufacturing Techniques ». Dans ASME 2005 International Mechanical Engineering Congress and Exposition. ASMEDC, 2005. http://dx.doi.org/10.1115/imece2005-82472.

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Scientific exploration into understanding and developing relationships between three-dimensional (3D) scaffolds prepared by rapid prototyping (RP) and cellular response has focused primarily on end results targeting osteoblast proliferation and differentiation. Here at the National Institute of Standards and Technology (NIST), we take a systems approach to developing relationships between material properties and quantitative biological responses. This study in particular focuses on the screening of parameters controlled by RP techniques and their ability to trigger signalling events leading to cell adhesion. This pioneering research in our group also characterizes the in vitro cell-material interactions of 2D films and 3D scaffolds. From there, one can postulate on contributory factors leading to cell migration, proliferation, and differentiation. In summary, we believe that the quantitative information from this fundamental investigation will enhance our knowledge of the interactions between cells and 3D material interfaces with respect to formation of focal adhesions. This work consists of two sections — the application of imaging techniques for 3D characterization of properties and culturing of osteoblasts for size and shape determination. This includes quantifying the number of focal adhesion sites. We are using 3D RP polycaprolactone (PCL) scaffolds as this surrogate model in which to compare 2D to 3D material performance and cell interactions. Using RP bio-manufacturing techniques to fabricate tissue engineering scaffolds allows for control of pore size, strut size, and layer thickness, therefore providing adjustable parameters to study which can potentially influence, or even dynamically modulate, cellular adhesion. Imaging results after culturing for 24 h showed differences in cell morphology and spreading relative to the different structures. The focal adhesion response also varied, indicating an apparent loss of organization in 3D scaffolds compared to 2D surfaces. See Results and Discussion for details.

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Rapports d'organisations sur le sujet "Screening, Signalling"

Miller, Gad, et Jeffrey F. Harper. Pollen fertility and the role of ROS and Ca signaling in heat stress tolerance. United States Department of Agriculture, janvier 2013. http://dx.doi.org/10.32747/2013.7598150.bard.

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The long-term goal of this research is to understand how pollen cope with stress, and identify genes that can be manipulated in crop plants to improve reproductive success during heat stress. The specific aims were to: 1) Compare heat stress dependent changes in gene expression between wild type pollen, and mutants in which pollen are heat sensitive (cngc16) or heat tolerant (apx2-1). 2) Compare cngc16 and apx2 mutants for differences in heat-stress triggered changes in ROS, cNMP, and Ca²⁺ transients. 3) Expand a mutant screen for pollen with increased or decreased thermo-tolerance. These aims were designed to provide novel and fundamental advances to our understanding of stress tolerance in pollen reproductive development, and enable research aimed at improving crop plants to be more productive under conditions of heat stress. Background: Each year crop yields are severely impacted by a variety of stress conditions, including heat, cold, drought, hypoxia, and salt. Reproductive development in flowering plants is highly sensitive to hot or cold temperatures, with even a single hot day or cold night sometimes being fatal to reproductive success. In many plants, pollen tube development and fertilization is often the weakest link. Current speculation about global climate change is that most agricultural regions will experience more extreme environmental fluctuations. With the human food supply largely dependent on seeds, it is critical that we consider ways to improve stress tolerance during fertilization. The heat stress response (HSR) has been intensively studied in vegetative tissues, but is poorly understood during reproductive development. A general paradigm is that HS is accompanied by increased production of reactive oxygen species (ROS) and induction of ROS-scavenging enzymes to protect cells from excess oxidative damage. The activation of the HSR has been linked to cytosolic Ca²⁺ signals, and transcriptional and translational responses, including the increased expression of heat shock proteins (HSPs) and antioxidative pathways. The focus of the proposed research was on two mutations, which have been discovered in a collaboration between the Harper and Miller labs, that either increase or decrease reproductive stress tolerance in a model plant, Arabidopsis thaliana (i.e., cngc16--cyclic nucleotide gated channel 16, apx2-1--ascorbate peroxidase 2,). Major conclusions, solutions, achievements. Using RNA-seq technology, the expression profiles of cngc16 and apx2 pollen grains were independently compared to wild type under favourable conditions and following HS. In comparison to a wild type HSR, there were 2,776 differences in the transcriptome response in cngc16 pollen, consistent with a model in which this heat-sensitive mutant fails to enact or maintain a normal wild-type HSR. In a comparison with apx2 pollen, there were 900 differences in the HSR. Some portion of these 900 differences might contribute to an improved HSR in apx2 pollen. Twenty-seven and 42 transcription factor changes, in cngc16 and apx2-1, respectively, were identified that could provide unique contributions to a pollen HSR. While we found that the functional HS-dependent reprogramming of the pollen transcriptome requires specific activity of CNGC16, we identified in apx2 specific activation of flavonol-biosynthesis pathway and auxin signalling that support a role in pollen thermotolerance. Results from this study have identified metabolic pathways and candidate genes of potential use in improving HS tolerance in pollen. Additionally, we developed new FACS-based methodology that can quantify the stress response for individual pollen in a high-throughput fashion. This technology is being adapted for biological screening of crop plant’s pollen to identify novel thermotolerance traits. Implications, both scientific and agricultural. This study has provided a reference data on the pollen HSR from a model plant, and supports a model that the HSR in pollen has many differences compared to vegetative cells. This provides an important foundation for understanding and improving the pollen HSR, and therefor contributes to the long-term goal of improving productivity in crop plants subjected to temperature stress conditions. A specific hypothesis that has emerged from this study is that pollen thermotolerance can be improved by increasing flavonol accumulation before or during a stress response. Efforts to test this hypothesis have been initiated, and if successful have the potential for application with major seed crops such as maize and rice.

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