Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2

The alpha,beta2,mu2,sigma2 heterotetrameric AP2 complex is recruited exclusively to the phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P(2))-rich plasma membrane where, amongst other roles, it selects motif-containing cargo proteins for incorporation into clathrin-coated vesicles. Unphosphorylated and mu2Thr156-monophosphorylated AP2 mutated in their alphaPtdIns4,5P(2), mu2PtdIns4,5P(2), and mu2Yxxvarphi binding sites were produced, and their interactions with membranes of different phospholipid and cargo composition were measured by surface plasmon resonance. We demonstrate that recognition of Yxxvarphi and acidic dileucine motifs is dependent on corecognition with PtdIns4,5P(2), explaining the selective recruitment of AP2 to the plasma membrane. The interaction of AP2 with PtdIns4,5P(2)/Yxxvarphi-containing membranes is two step: initial recruitment via the alphaPtdIns4,5P(2) site and then stabilization through the binding of mu2Yxxvarphi and mu2PtdIns4,5P(2) sites to their ligands. The second step is facilitated by a conformational change favored by mu2Thr156 phosphorylation. The binding of AP2 to acidic-dileucine motifs occurs at a different site from Yxxvarphi binding and is not enhanced by mu2Thr156 phosphorylation

Statistical features of edge turbulence in RFX-mod from Gas Puffing Imaging

Plasma density fluctuations in the edge plasma of the RFX-mod device are measured through the Gas Puffing Imaging Diagnostics. Statistical features of the signal are quantified in terms of the Probability Distribution Function (PDF), and computed for several kinds of discharges. The PDFs from discharges without particular control methods are found to be adequately described by a Gamma function, consistently with the recent results by Graves et al [J.P. Graves, et al, Plasma Phys. Control. Fusion 47, L1 (2005)]. On the other hand, pulses with external methods for plasma control feature modified PDFs. A first empirical analysis suggests that they may be interpolated through a linear combination of simple functions. An inspection of the literature shows that this kind of PDFs is common to other devices as well, and has been suggested to be due to the simultaneous presence of different mechanisms driving respectively coherent bursts and gaussian background turbulence. An attempt is made to relate differences in the PDFs to plasma conditions such as the local shift of the plasma column. A simple phenomenological model to interpret the nature of the PDF and assign a meaning to its parameters is also developed.Comment: 27 pages. Published in PPC

A serine protease secreted from Bacillus subtilis cleaves human plasma transthyretin to generate an amyloidogenic fragment

Aggregation of human wild-type transthyretin (hTTR), a homo-tetrameric plasma protein, leads to acquired senile systemic amyloidosis (SSA), recently recognised as a major cause of cardiomyopathies in 1-3% older adults. Fragmented hTTR is the standard composition of amyloid deposits in SSA, but the protease(s) responsible for amyloidogenic fragments generation in vivo is(are) still elusive. Here, we show that subtilisin secreted from Bacillus subtilis, a gut microbiota commensal bacterium, translocates across a simulated intestinal epithelium and cleaves hTTR both in solution and human plasma, generating the amyloidogenic fragment hTTR(59-127), which is also found in SSA amyloids in vivo. To the best of our knowledge, these findings highlight a novel pathogenic mechanism for SSA whereby increased permeability of the gut mucosa, as often occurs in elderly people, allows subtilisin (and perhaps other yet unidentified bacterial proteases) to reach the bloodstream and trigger generation of hTTR fragments, acting as seeding nuclei for preferential amyloid fibrils deposition in the heart. Peterle et al. show that a subtilisin like serine protease secreted from gut microbiota Bacillus subtilis cleaves the wild-type human transthyretin (hTTR) to generate an amyloidogenic peptide. High propensity of the hTTR fragment to form pathogenic protein aggregates implicates the serine protease in the pathogenesis of acquired senile systemic amyloidosis

Electromagnetic turbulent structures: A ubiquitous feature of the edge region of toroidal plasma configurations

Electromagnetic features of turbulent filaments, emerging from a turbulent plasma background, have been studied in four different magnetic configurations: the stellarator TJ-II, the Reversed Field Pinch RFX-mod, a device that can be operated also as a ohmic tokamak, and the Simple Magnetized Torus, TORPEX. By applying an analogous diagnostic concept in all cases, direct measurements of both field-aligned current density and vorticity were performed inside the filament. The inter-machine comparison reveals a clear dependence of the filament vorticity upon the local time-averaged E x B flow shear. Furthermore, a wide range of local beta was explored allowing concluding that this parameter plays a fundamental role in the appearance of filament electromagnetic features

Spectroscopy near the proton drip line in the deformed A=130 mass region : the Pr-126 nucleus

The near proton drip line nucleus Pr-126 was studied via in-beam gamma-ray spectroscopy using the Ca-40 + Mo-92 reaction at 190 MeV. We observed for the first time excited states above the known isomer in this nucleus up to 31 h over bar. The observed band is discussed in the interacting boson-fermion-fermion model.The calculations and the experimental information suggest a spin 8(+) for the lowest observed state.With such a spin assignment the moment of inertia of Pr-126 gets larger than in the heavier Pr isotopes, suggesting a sudden change in deformation close to the proton drip line

Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

Gamma-ray Tracking with Segmented HPGe Detectors

This paper gives a brief overview of the technical progress that can be achieved with the newly available segmented HPGe detectors. Gamma-ray tracking detectors are a new generation of HPGe detectors which are currently being developed to improve significantly the efficiency and resolving power of the 4 … germanium detectors arrays for high-precision ∞-ray spectroscopy. They consist of highly segmented HPGe detectors associated with fast digital front-end electronics. Through the pulse-shape analysis of the signals it is possible to extract the energy, timing and spatial information on the few interactions a ∞-ray undergoes in the HPGe detector. The tracks of the ∞-rays in the HPGe detector can then be reconstructed in three dimensions based on the Compton scattering formula. Such a detector has been used for the first time during an in-beam experiment. The ∞-decay of the Coulomb excitation of a 56 Fe nucleus was measured with the highly segmented MARS prototype positioned at 135 degree. The energy resolution has been improved by a factor of 3 as compared to standard HPGe detectors due to very precise Doppler correction based on knowledge of the ∞-ray track. I Introduction The future facilities for radioactive beams will allow, for the first time, the exploration of a new large area of the nuclear landscape. In connection with the study of the ∞-radiation, it is important to point out that the intensity of such radioactive beams is expected to be much smaller than that of stable beams, Doppler Effects in many experiments are expected to be much stronger and an intense background of X-rays could be present. Consequently, a new generation of powerful HPGe arrays with segmented detectors is being designed. Both in USA and in Europe several projects, based on segmented HPGe detectors, have already started and are in an advanced status of realization. The objective of the more recent R&D efforts is to improve the total efficiency by removing the BGO shields without affecting the P/T ratio with the use of the tracking technique, namely the reconstruction of the ∞-ray path to identify the ∞-incident direction (for the Doppler correction), the removal of the background and to check whether or not the ∞ was fully absorbed in the array. Such development implies unprecedented R&D efforts where completely new technology has to be applied, tested or developed in all the constituents of an HPGe array, from the detector to the front-end electronics. The typical feature of the energy deposition of a ∞-ray is that of interacting in a limited number of positions. ∞-tracking of this hits is a very challenging and ambitious task. First, one has to identify, isolate and localize each hit inside a segmented detector with pulse shape analysis based on the study of the physical mechanism of the pulse generation or with Artificial Intelligence techniques (like Neural Networks or Genetic Algorithm [1]) of the direct and induced electrical pulses produced by every interacting ∞-rays. Second, a tracking algorithm has to reconstruct the real trajectory from the list of interaction points through statistical techniques. The result is expected to be the complete reconstruction of the track of the incident ∞, namely the complete description of the interacting ∞-ray. Worldwide efforts have been done using simulations and proof-of-principle measurements and turned out to be successful. The feasibility of the entire process of ∞ray tracking is demonstrated in this paper based on an experiment, done at the LNL in Italy, using the MARS prototype detector

Resistive g-modes in a reversed field pinch plasma

First direct experimental evidence of high frequency, high toroidal mode number (n>20), magnetic fluctuations due to unstable resistive interchange modes (g-modes) resonant in the edge region of a reversed field pinch (RFP) plasma is presented. Experimental characterization of time and space periodicities of the modes is provided by means of highly resolved in-vessel edge and insertable magnetic diagnostics. It is found that the spectral mode properties are in good agreement with the predictions of the theoretical linear resistive magnetohydrodynamic stability analysis. A simple model is proposed for the observed saturation levels of the modes.Comment: Submitted to Physical Review Letter

The plasma boundary in Single Helical Axis RFP plasmas

Single Helical Axis (SHAx) states obtained in high current reversed field pinch (RFP) plasmas display, aside from a dominant mode in the m=1 spectrum, also a dominant m=0 mode, with the same toroidal mode number as the m=1 one. The two modes have a fixed phase relationship. The island chain created by the m=0 mode across the reversal surface gives rise, at shallow reversal of the toroidal field, to an X-point structure which separates the last closed flux surface from the first wall, creating a divertor-like configuration. The plasma-wall interaction is found to be related to the connection length of the field lines intercepting the wall, which displays a pattern modulated by the dominant mode toroidal periodicity. This configuration, which occurs only for shallow toroidal field reversal, could be exploited to realize an island divertor in analogy to stellarators.Comment: 12 pages, 9 figures Submitted to Nuclear Fusio