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The mechanism by which the cytosolic protein Zap70 physically interacts with and phosphorylates its substrate, the transmembrane protein LAT, upon T cell receptor (TCR) stimulation remains largely obscure. In this study, we found that the pharmacological inhibition of formins, a major class of actin nucleators, suppressed LAT phosphorylation by Zap70, despite TCR stimulation-dependent phosphorylation of Zap70 remaining intact. High-resolution imaging and three-dimensional image reconstruction revealed that localization of phosphorylated Zap70 to the immune synapse (IS) and subsequent LAT phosphorylation are critically dependent on formin-mediated actin polymerization. Using knockout mice, we identify mDia1 and mDia3, which are highly expressed in T cells and which localize to the IS upon TCR activation, as the critical formins mediating this process. Our findings therefore describe previously unsuspected roles for mDia1 and mDia3 in the spatiotemporal control of Zap70-dependent LAT phosphorylation at the IS through regulation of filamentous actin, and underscore their physiological importance in TCR signaling.

© 2016, the Meteorological Society of Japan. We describe two unprecedented large (100-member), longterm (61-year) ensembles based on MRI-AGCM3.2, which were driven by historical and non-warming climate forcing. These ensembles comprise the "Database for Policy Decision making for Future climate change (d4PDF)". We compare these ensembles to large ensembles based on another climate model, as well as to observed data, to investigate the influence of anthropogenic activities on historical changes in the numbers of record-breaking events, including: the annual coldest daily minimum temperature (TNn), the annual warmest daily maximum temperature (TXx) and the annual most intense daily precipitation event (Rx1day). These two climate model ensembles indicate that human activity has already had statistically significant impacts on the number of record-breaking extreme events worldwide mainly in the Northern Hemisphere land. Specifically, human activities have altered the likelihood that a wider area globally would suffer record-breaking TNn, TXx and Rx1day events than that observed over the 2001- 2010 period by a factor of at least 0.6, 5.4 and 1.3, respectively. However, we also find that the estimated spatial patterns and amplitudes of anthropogenic impacts on the probabilities of record-breaking events are sensitive to the climate model and/or natural-world boundary conditions used in the attribution studies.

The experimental studies on zonal flows and turbulence have been carried out in Compact Helical System [K. Matsuoka, S. Kubo, M. Hosokawa, in Plasma Physics and Controlled Nuclear Fusion Research, Proc. 12th Int. Conf., Nice, 1988 (International Atomic Energy Agency, Vienna, 1989, Vol. 2, p. 411] using twin heavy ion beam probes. The paper presents the experimental observations of stationary zonal flow, nonlinear couplings between zonal flow and turbulence, and the role of zonal flow in the improved confinement, together with the recent discovery of zonal magnetic field. The presented experimental results strongly support the new paradigm that the plasma transport should be considered as a system of drift wave and zonal flows, and provides the first direct evidence for turbulence dynamo that the structured magnetic field can be really generated by turbulence. © 2008 American Institute of Physics.

A zonal magnetic field is found in a toroidal plasma. The magnetic field has a symmetric bandlike structure, which is uniform in the toroidal and poloidal directions and varies radially with a finite wavelength of mesoscale, which is analogous to zonal flows. A time-dependent bicoherence analysis reveals that the magnetic field should be generated by the background plasma turbulence. The discovery is classified as a new kind of phenomenon of structured magnetic field generation, giving insight into phenomena such as dipole field generation in rotational planets.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the downregulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.