Thrombin Protease-activated Receptor-1 Signals through Gq- and G13-initiated MAPK Cascades Regulating c-Jun Expression to Induce Cell Transformation

Although the ability of G protein-coupled receptors to stimulate normal and aberrant cell growth has been intensely investigated, the precise nature of the molecular mechanisms underlying their transforming potential are still not fully understood. In this study, we have taken advantage of the potent mitogenic effect of thrombin and the focus-forming activity of one of its receptors, protease-activated receptor-1, to dissect how this receptor coupled to Gi, Gq/11, and G12/13 transduces signals from the membrane to the nucleus to initiate transcriptional events involved in cell transformation. Using endogenous and transfected thrombin receptors in NIH 3T3 cells, ectopic expression of muscarinic receptors coupled to Gq and Gi, and chimeric G protein subunits and murine fibroblasts deficient in Gq/11, and G12/13, we show here that, although coupling to Gi is sufficient to induce ERK activation, the ability to couple to Gq and/or G13 is necessary to induce c-jun expression and cell transformation. Furthermore, we show that Gq and G13 can initiate the activation of MAPK cascades, including JNK, p38, and ERK5, which in turn regulate the activity of transcription factors controlling expression from the c-jun promoter. We also present evidence that c-Jun and the kinases regulating its expression are integral components of the transforming pathway initiated by protease-activated receptor-1

Earthworms, soil-aggregates and organic matter decomposition in agro-ecosystems in the Netherlands

The relationships between earthworm populations, soil aggregate stability and soil organic matter dynamics were studied at an experimental farm in The Netherlands.Arable land in general is not favourable for earthworm growth. In the Lovinkhoeve fields under conventional management earthworm populations were brought to the verge of extinction in a few years. Main causes are soil fumigation against nematodes and unfavourable food conditions. Organic matter inputs and N-contents of the organic materials are important aspects of food availability of earthworms, but also bacterial and protozoan biomass play a role. Natural stress, such as summer drought and winter frost, adds to the effects of management. Organic management with reduced pesticide use, however, strongly stimulates population development. Colonisation, especially stimulated in the presence of passive transport mechanisms can help population built up. Population parameters and growth conditions at the invaded plots further influence the speed of colonisation.Correlation studies, combined with results of manipulation experiments show that earthworms increase resistance against slaking of field macro-aggregates. Fresh earthworm casts are very unstable, but their stability increases during ageing by several mechanisms. Drying makes casts much more stable than dried uningested field aggregates. Under specific conditions, fungal growth on the surface may stabilise wet casts, but the rearrangement of clay around particulate organic material seems to be the most important process for development of stability during ageing. Microbial activity either in the gut or after excretion may play an indirect role in connecting the organic material and the clay.The organic matter included in stable aggregates formed under the influence of earthworms is much better protected against microbial breakdown during the lifetime of these aggregates than organic matter in stable aggregates formed by other mechanisms. In the presence of earthworms, stable aggregates are either formed at a higher rate or break down at a lower rate. Also, earthworm activity can lead to increased organic matter contents of macro-aggregates. Earthworm activity consequently leads to a concentration of organic matter in the larger aggregate fraction and to a higher organic matter retention capacity of the soil. Grinding soil to fragments smaller than 2 mm, as is often done in standard procedures, will strongly influence organic matter breakdown in incubation experiments in samples from soils with high earthworm activity. Therfore, these standard preteatment methods are unsuitable for fractionation and decomposition studies

..., 83106786, 114382724, 1509048322, 2343463290, 27410087742, ... Efficient Hilbert Series for Effective Theories

We present an efficient algorithm for determining the Hilbert series of an effective theory and provide a companion code called ECO (Efficient Counting of Operators) in FORM. For example, the Hilbert series for the dimension 15 operators in the Standard Model Effective Theory (SMEFT) can be obtained in a minute on a single CPU core. While our implementation focusses on SMEFT, we allow for a flexible user input of the light degrees of freedom. Furthermore, gravity, as well as additional U(1) global or gauge symmetries can be included.Comment: 9 pages, no figures, FORM files include

The composition of concert music within the Digital Audio Workstation environment.

This research project includes a portfolio of compositions and a contextual document, the subject of which is the Digital Audio Workstation as a human computer interface for the composition of concert music, intended for live performance. The portfolio of compositions consists of the music notation and audio recordings of five works, composed by the researcher within the context of the research project: Variances for jazz guitar, piano, percussion and indeterminate ensemble; Rapprochement for microtonal ensemble; Transits for bass flute, eight voices and electronics; Shutterspeed for clarinet and soundtrack; and Fossils for piano and live electronics. For each of the works, a distinct DAW-based concept and compositional approach has been developed and employed. The contextual document investigates the implications of the DAW for the composition of concert music, and discusses the five portfolio compositions against the background of practices of selected composers; the history and development of the analogue studio, early computer and DAW composition; aspects of device interaction; and the topic of 'liveness'

The small GTP-binding protein RhoA regulates c-Jun by a ROCK-JNK signaling axis

RhoA regulates the actin cytoskeleton and the expres- sion of genes associated with cell proliferation. This includes c-fos and c-jun, which are members of the AP1 family of transcription factors that play a key role in normal and aberrant cell growth. Whereas RhoA stimulates the c-fos SRE by a recently elucidated mechanism that is dependent on actin treadmilling, how RhoA regulates c-jun is still poorly understood. We found that RhoA stimulates c-jun expression through ROCK, but independently from the ability of ROCK to promote actin polymerization. Instead, we found that ROCK activates JNK, which then phosphor- ylates c-Jun and ATF2 when bound to the c-jun pro- moter. Thus, ROCK represents a point of signal diver- gence downstream from RhoA, as it promotes actin reorganization and the consequent expression from the c-fos SRE, while a parallel pathway connects ROCK to JNK, thereby stimulating c-jun expression. Ultimately, these pathways converge in the nucleus to regulate AP1 activity