Regulation of Aurora Kinases and Their Activity

The three mitotic protein kinases Aurora-A, B and C are complementary enzymes that regulate multiple mitotic events. To do so, the different kinases must be locally activated, and the control of their activity is tightly regulated in time and space during mitosis. For instance, Aurora-A is first active at the centrosomes, then on microtubules at the spindle pole, Aurora-B is active in the nucleus, then at chromosome kinetochores and later one at the midbody. Aurora kinase activity is regulated in space and time by locally binding to regulators. Aurora kinases must bind to protein partners to be activated. Aurora-A for instance binds to targeting protein for Xenopus kinesin-like protein 2 (TPX2) and is activated at the spindle pole, Aurora-B and Aurora-C to INner CENtromer Protein (INCENP) and is activated on the chromosomes. These activations go through an autophosphorylation of a threonine residue in the T-loop of the kinase. Other protein partners are using different mechanisms to activate Auroras. These allow activation of the kinase at different time and location in the cell. This review is an up-to-date list of regulators of Aurora kinases. The subcellular localization of these regulators explains the presence of an active Aurora kinase. It also explains the changes in the localizations of the Aurora kinases activity observed during cell cycle progression in mitosis. Aurora kinases have been recently reported to be involved in nonmitotic events, and the identity of their activators in these events must be searched

Fatigue behaviour of additively manufactured Ti-6Al-4V alloy: The role of defects on scatter and statistical size effect

This work is focused on the influence of defects on scatter and statistical size effect of Ti-6Al-4V alloy fabricated by the SLM process. A vast fatigue test campaign has been undertaken, for two surface conditions (as-built and machined surfaces) and two specimen geometries with different highly loaded volume sizes. It was shown, for machined specimens, that a large variety of crack initiation mechanisms is the principal origin of the fatigue scatter. Regarding the size effect, the change of the mechanism is the first order factor that governs the size effect. For as-built specimens, these effects are much less pronounced

Electronic temperatures, densities and plasma X-ray emission of a 14.5 GHz Electron-Cyclotron Resonance Ion Source

We have performed a systematic study of the Bremsstrahlung emission from the electrons in the plasma of a commercial 14.5 GHz Electron-Cyclotron Resonance Ion Source. The electronic spectral temperature and the product of ionic and electronic densities of the plasma are measured by analyzing the Bremsstrahlung spectra recorded for several rare gases (Ar, Kr, Xe) as a function of the injected power. Within our uncertainty, we find an average temperature of ? 48 keV above 100W, with a weak dependency on the injected power and gas composition. Charge state distributions of extracted ion beams have been determined as well, providing a way to disentangle the ionic density from the electronic density. Moreover X-ray emission from highly charged argon ions in the plasma has been observed with a high-resolution mosaic crystal spectrometer, demonstrating the feasibility for high-precision measurements of transition energies of highly charged ions, in particular of the magnetic dipole (M1) transition of He-like of argon ions

Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling

The Na+/H+ exchanger NHE1 is a highly regulated membrane protein that is required for pH homoeostasis in cardiomyocytes. The activation of NHE1 leads to proton extrusion, which is essential for counteracting cellular acidity that occurs following increased metabolic activity or ischaemia. The activation of NHE1 intrinsic catalytic activity has been well characterized and established experimentally. However, we have examined in the present study whether a net translocation of NHE1 to the sarcolemma of cardiomyocytes may also be involved in the activation process. We have determined the distribution of NHE1 by means of immunofluorescence microscopy and cell-surface biotinylation. We have discovered changes in the distribution of NHE1 that occur when cardiomyocytes are stimulated with insulin that are PI3K (phosphoinositide 3-kinase)-dependent. Translocation of NHE1 also occurs when cardiomyocytes are challenged by hypoxia, or inhibition of mitochondrial oxidative metabolism or electrically induced contraction, but these responses occur through a PI3K-independent process. As the proposed additional level of control of NHE1 through translocation was unexpected, we have compared this process with the well-established translocation of the glucose transporter GLUT4. In immunofluorescence microscopy comparisons, the translocation of NHE1 and GLUT4 to the sarcolemma that occur in response to insulin appear to be very similar. However, in basal unstimulated cells the two proteins are mainly located, with the exception of some co-localization in the perinuclear region, in distinct subcellular compartments. We propose that the mechanisms of translocation of NHE1 and GLUT4 are linked such that they provide spatially and temporally co-ordinated responses to cardiac challenges that necessitate re-adjustments in glucose transport, glucose metabolism and cell pH

Rising atmospheric methane: 2007-2014 growth and isotopic shift

From 2007 to 2013, the globally averaged mole fraction of methane in the atmosphere increased by 5.7±1.2ppb yr$^{-1}$. Simultaneously, $\delta^{13}$C$_\text{CH4}$ (a measure of the $^{13}$C/$^{12}$C isotope ratio in methane) has shifted to significantly more negative values since 2007. Growth was extreme in 2014, at 12.5±0.4ppb, with a further shift to more negative values being observed at most latitudes. The isotopic evidence presented here suggests that the methane rise was dominated by significant increases in biogenic methane emissions, particularly in the tropics, for example, from expansion of tropical wetlands in years with strongly positive rainfall anomalies or emissions from increased agricultural sources such as ruminants and rice paddies. Changes in the removal rate of methane by the OH radical have not been seen in other tracers of atmospheric chemistry and do not appear to explain short-term variations in methane. Fossil fuel emissions may also have grown, but the sustained shift to more $^{13}$C-depleted values and its significant interannual variability, and the tropical and Southern Hemisphere loci of post-2007 growth, both indicate that fossil fuel emissions have not been the dominant factor driving the increase. A major cause of increased tropical wetland and tropical agricultural methane emissions, the likely major contributors to growth, may be their responses to meteorological change.This work was supported by the UK Natural Environment Research Council projects NE/N016211/1 The Global Methane Budget, NE/M005836/1 Methane at the edge, NE/K006045/1 The Southern Methane Anomaly and NE/I028874/1 MAMM. We thank the UK Meteorological Office for flask collection and hosting the continuous measurement at Ascension, the Ascension Island Government for essential support, and Thumeka Mkololo for flask collection in Cape Tow

The Spatial Architecture of Bacillus subtilis Biofilms Deciphered Using a Surface-Associated Model and In Situ Imaging

The formation of multicellular communities known as biofilms is the part of bacterial life cycle in which bacteria display cooperative behaviour and differentiated phenotypes leading to specific functions. Bacillus subtilis is a Gram-positive bacterium that has served for a decade as a model to study the molecular pathways that control biofilm formation. Most of the data on B. subtilis biofilms have come from studies on the formation of pellicles at the air-liquid interface, or on the complex macrocolonies that develop on semi-solid nutritive agar. Here, using confocal laser scanning microcopy, we show that B. subtilis strains of different origins are capable of forming biofilms on immersed surfaces with dramatically protruding “beanstalk-like” structures with certain strains. Indeed, these structures can reach a height of more than 300 µm with one undomesticated strain from a medical environment. Using 14 GFP-labeled mutants previously described as affecting pellicle or complex colony formation, we have identified four genes whose inactivation significantly impeded immersed biofilm development, and one mutation triggering hyperbiofilm formation. We also identified mutations causing the three-dimensional architecture of the biofilm to be altered. Taken together, our results reveal that B. subtilis is able to form specific biofilm features on immersed surfaces, and that the development of these multicellular surface-associated communities involves regulation pathways that are common to those governing the formation of pellicle and/or complex colonies, and also some specific mechanisms. Finally, we propose the submerged surface-associated biofilm as another relevant model for the study of B. subtilis multicellular communities

Experience Using a Distributed Object Oriented Database for a Daq System

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A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues

STUDIES ON SWITCH-BASED EVENT BUILDING SYSTEMS IN RD13

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