Regulation of cell signalling by uPAR Smith, Harvey W; Marshall, Chris J
Nature reviews. Molecular cell biology,
201001, 2010-Jan, 2010-01-00, 20100101, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation and tissue remodelling and in many human cancers, in which it frequently indicates poor prognosis. uPAR ...regulates proteolysis by binding the extracellular protease urokinase-type plasminogen activator (uPA; also known as urokinase) and also activates many intracellular signalling pathways. Coordination of extracellular matrix (ECM) proteolysis and cell signalling by uPAR underlies its important function in cell migration, proliferation and survival and makes it an attractive therapeutic target in cancer and inflammatory diseases. uPAR lacks transmembrane and intracellular domains and so requires transmembrane co-receptors for signalling. Integrins are essential uPAR signalling co-receptors and a second uPAR ligand, the ECM protein vitronectin, is also crucial for this process.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We study the feasibility of using neutrino-electron elastic scattering to measure the neutrino flux in the DUNE neutrino oscillation experiment. The neutrino-electron scattering cross section is ...precisely known, and the kinematics of the reaction allow the determination of the incoming neutrino energy by precise measurement of the energy and angle of the recoiling electron. For several possible near detectors, we perform an analysis of their ability to measure neutrino flux in the presence of backgrounds and uncertainties. With realistic assumptions about detector masses, we find that a liquid argon detector, even with limitations due to angular resolution, is able to perform better than less dense detectors with more precise event-by-event neutrino energy measurements. We find that the absolute flux normalization uncertainty can be reduced from ∼8% to ∼2%, and the uncertainty on the flux shape can be reduced by ∼20%–30%.
Proinflammatory cytokines are frequently observed in the tumor microenvironment, and chronic inflammation is involved in cancer initiation and progression. We show that cytokine signaling through the ...receptor subunit GP130-IL6ST and the kinase JAK1 generates actomyosin contractility through Rho-kinase dependent signaling. This pathway generates contractile force in stromal fibroblasts to remodel the extracellular matrix to create tracks for collective migration of squamous carcinoma cells and provides the high levels of actomyosin contractility required for migration of individual melanoma cells in the rounded, “amoeboid” mode. Thus, cytokine signaling can generate actomyosin contractility in both stroma and tumor cells. Strikingly, actomyosin contractility itself positively modulates activity of the transcription factor STAT3 downstream of JAK1, demonstrating positive feedback within the signaling network.
► Cytokines signal via JAK1 to actomyosin contractility in tumor cells and stroma ► JAK1 signals to matrix remodelling in CAFs ► JAK1 signals to rounded/amoeboid movement of melanoma cells ► Round cells are found at invasive fronts of melanoma and stain for phospho-STAT3
Rho GTPases Sadok, Amine; Marshall, Chris J
Small GTPases,
10/2/2014, Letnik:
5, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Since their discovery in the late eighties, the role of Rho GTPases in the regulation of cell migration has been extensively studied and has mainly focused on the hallmark family members Rho, Rac, ...and Cdc42. Recent technological advances in cell biology, such as Rho-family GTPase activity biosensors, studies in 3D, and unbiased RNAi-based screens, have revealed an increasingly complex role for Rho GTPases during cell migration, with many inter-connected functions and a strong dependency on the physical and chemical properties of the surrounding environment. This review aims to give an overview of recent studies on the role of Rho-family GTPase members in the modulation of cell migration in different environments, and discuss future directions.
Neutrino interactions with nuclei have been the subject of intense interest during the last 15 years. Current and future measurements of neutrino oscillation and exotic physics use order 0.1-10 GeV ...neutrinos on a range of nuclear targets (
12
C,
16
O,
40
Ar). As the precision of these experiments has increased, information from their detectors and dedicated experiments has indicated deficiencies in the modeling of neutrino interactions on nuclear targets. Here, we present the current state of knowledge about neutrino-nucleus interactions, the challenge of extracting the cross section of these processes, and current experimental puzzles in the field. We also look forward to new and novel measurements and future efforts that seek to resolve these questions.
The increasing popularity of ultra-wideband (UWB) technology for location-based services, such as access control and real-time indoor track&tracing, as well as UWB support in new consumer devices ...such as smartphones, has resulted in the availability of multiple new UWB radio chips. However, due to this increase in UWB device availability, the question of which (industry) standards and configuration factors impact UWB interoperability and compatibility becomes increasingly important. In this paper, the fundamentals of UWB compatibility are investigated by first giving an overview of different UWB radio chips on the market. After that, an overview of UWB standards and organizations is given. Next, this overview is used to discuss the focus of these different standards and to identify the differences between them. We describe compatibility issues and associated interoperability aspects related to physical (PHY), medium-access-control (MAC) and upper layers. For the PHY layer, compatibility is possible for all UWB radio chips if the correct settings are configured. For the MAC layer, the implementation of the multiple access scheme as well as the localization technique is mostly proprietary. For the device discovery, several standards are currently being drafted. Finally, future challenges related to UWB interoperability are discussed.
Uses a restorative inquiry framework to understand the impacts and needs of health practitioners arising from an event that led to an investigation by the Health and Disability Commissioner (HDC). ...Proposes a relational approach to justice whereby people involved come together to speak truthfully about what happened and its impact on their lives, to clarify accountability, and to resolve together how best to repair relationships and prevent further harm. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
This study examines whether Situational Action Theory (SAT) can explain variation in delinquent offending between countries grouped along shared moral values. Thirteen countries were categorised in ...terms of "contextual morality" according to results from the World Values Survey. Then, survey data from a cross-section of 12 to 16-year-old youths in the International Self-Report Delinquency Study (ISRD3) were employed to test hypotheses that SAT operates differently between countries in "low contextual morality" and "high contextual morality" clusters. Multivariate analyses reveal that SAT is a generalisable theory of offending, since criminal propensity, self-control and personal morality operate in both low and high contextual morality country clusters. While exposure to criminogenic influence is the most salient, it is significantly higher in the "high contextual morality" cluster, suggesting that delinquent behaviour is more frequent when there is inconsistency between personal morality and the broader moral context. We conclude with implications for theory and policy.
This study explores the generalizability of Situational Action Theory (SAT) in India by testing hypotheses related to the person–environment interaction in explaining offending. Drawing on data from ...a sample of 872 students between the ages of 14 and 17 from an Indian city collected as part of the International Self-Report Delinquency Study (ISRD3), we tested the hypothesis that Indian youths will report more delinquent acts if they have a higher propensity to commit crime combined with a greater exposure to criminogenic activities. Our findings show unequivocal support for the applicability of SAT in India where youths reported a slight increase in offending behavior if they exercised low self-control or if they were less moralistic (i.e., they were more crime-prone), or when exposed to criminal activities or peers. Consistent with tests of SAT in other contexts, we find that exposure to criminogenic environments increases offending for youth with higher levels of criminal propensity but does not impact youth with lower levels of criminal propensity. We speculate that the overall low rate of delinquent offending coupled with the cultural milieu of Indian youths may explain why criminogenic exposure may be less relevant in light of young people’s strong avoidance of rule-breaking.
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