Dynamics of the pedestal transport during edge localized mode cycles at ASDEX Upgrade

The dynamic behaviour of the ion and electron energy, particle and momentum transport measured during type-I edge localized mode (ELM) cycles at ASDEX Upgrade is presented. Fast measurements of the ion and electron temperature profiles revelead that the ion and electron energy transport recover on different timescales, with the electrons recovering on a slower timescale (Cavedon et al 2017 Plasma Phys. Control. Fusion 59 105007). The dominant mechanism for the additional energy transport in the electron channel that could cause the delay in the electron temperature gradient (VTe) recovery is attributed to the depletion of energy caused by the ELM. The local sources and sinks for the electron channel in the steep gradient region are much smaller compared to the energy flux arriving from the pedestal top, indicating that the core plasma may dictate the local dynamics of the VTe recovery during the ELM cycle. A model for the edge momentum transport based on toroidal torque balance that takes into account the existence of poloidal impurity asymmetries has been developed. The analysis of the profile evolution during the ELM cycle shows that the model captures the dynamics of the rotation both before the ELM crash and during the recovery phase.European Commission (Euratom) Grant agreement No. 633053H2020 Marie-Sklodowska Curie programme (grant agreement No. 708257)European Union’s Horizon 2020 (grant agreement No. 805162

PLASMA SHAPE AND FUELING DEPENDENCE ON THE SMALL ELMS REGIME IN TCV AND AUG

A series of experiments has been conducted at AUG and TCV to disentangle the role of fueling, plasma triangularity and closeness to a double null (DN) configuration for the onset of the small ELM regime. At AUG, the role of the SOL density has been revisited. Indeed, it turns out that a large density SOL is not a sufficient condition to achieve the type-II (small) ELM regime. This has been demonstrated with a constant gas fueled plasma close to DN which has been progressively shifted down, relaxing therefore the closeness to DN at constant. As the plasma is moved down, Type-I ELMs are progressively restored, finally being the unique ELM regime. It is observed that not only the pedestal top profiles are unchanged, but also the SOL profiles remained unaffected by transition from Type-II to Type-I ELMs. We conclude that the separatrix density is not the unique key parameter and it is hypothesized that the local magnetic shear, modified by the closeness to DN, could play an important role. A small ELM regime with good confinement has been achieved at TCV, a full carbon machine featuring an open divertor. A systematic scan in the fueling rate has been done for both medium and high triangularity shapes. For the latter case, a configuration close to a DN configuration, the stored energy and the pedestal top pressure increase by 5% and 30% respectively compared to the medium triangularity case. For both shapes, as the D2 fueling is increased, the Type-I ELM frequency decreases and small ELMs are observed in between large ones. Finally for the high triangularity, at the maximum fueling rate, the large ELMs are fully suppressed and only the small ELMs remain. As observed in JET and AUG, the pedestal pressure degrades with increasing fueling, up to 40% for the high triangularity scenario, although the stored energy remains almost unchanged. It is also observed that, for both shapes, the density at the separatrix increases with the fueling rate, reaching ne,sep/nG ~0.3 at ne,av/nG~0.75. The small ELM regime at TCV is associated with a coherent mode at about 30 kHz seen by the magnetic probes located at the outboard midplane. The outer target heat loads from IR tomography are reduced by more than a factor of 5 when transiting towards the small ELM regime

Proliferation of nutrition sensing preadipocytes upon short term HFD feeding

Adipose tissue is highly dynamic and increases its size dependent on the status of nutrition. Generally, an increase of adipose tissue mass is attributed to two mechanisms, namely hypertrophy (increase in adipocyte size) and hyperplasia (increase in adipocyte number). Here, we analyzed the proliferation capacity of a pool of nutrition sensing preadipocytes after short-term high fat diet (HFD) feeding. We show that this process is age independent and that adipocyte hyperplasia seems not to be dependent on adipocyte hypertrophy. Further, we could show that the subsequent development into adipocytes is influenced by the duration of HFD feeding after proliferation. Our data also demonstrate that the studied pool of preadipocytes seems to be finite and cannot be reactivated by multiple bouts of HFD feeding. In conclusion, our results indicate an important link between stem cells, nutrition status and homeostasis in the epididymal adipose tissue

A Modified Secondary Task Reaction Time Paradigm for Research on Breaks in Presence

Breaks in presence are considered a promising approach to investigate events where users are pulled out of their virtual experiences. In this paper, we argue that this methodology may also provide insights into the cognitive processes behind the presence experience. To this end, we combined breaks in presence with a modified version of the secondary task reaction times paradigm and psychophysiological measures to tap into the attentional processes behind presence experiences. 69 participants played a modified video game, during which they had to react to sounds that were either part of the story or unrelated (breaks in presence) as a secondary task. We measured their reaction times to both sound types, skin conductance responses and heart rate variability. Participants reacted equally fast to virtual and BIP-eliciting stimuli. Both types of stimuli elicit orienting responses with our virtual stimulus leading to stronger responses and habitualization. Avenues for future research are discussed

The GTP- and Phospholipid-Binding Protein TTD14 Regulates Trafficking of the TRPL Ion Channel in Drosophila Photoreceptor Cells.

Recycling of signaling proteins is a common phenomenon in diverse signaling pathways. In photoreceptors of Drosophila, light absorption by rhodopsin triggers a phospholipase Cβ-mediated opening of the ion channels transient receptor potential (TRP) and TRP-like (TRPL) and generates the visual response. The signaling proteins are located in a plasma membrane compartment called rhabdomere. The major rhodopsin (Rh1) and TRP are predominantly localized in the rhabdomere in light and darkness. In contrast, TRPL translocates between the rhabdomeral plasma membrane in the dark and a storage compartment in the cell body in the light, from where it can be recycled to the plasma membrane upon subsequent dark adaptation. Here, we identified the gene mutated in trpl translocation defective 14 (ttd14), which is required for both TRPL internalization from the rhabdomere in the light and recycling of TRPL back to the rhabdomere in the dark. TTD14 is highly conserved in invertebrates and binds GTP in vitro. The ttd14 mutation alters a conserved proline residue (P75L) in the GTP-binding domain and abolishes binding to GTP. This indicates that GTP binding is essential for TTD14 function. TTD14 is a cytosolic protein and binds to PtdIns(3)P, a lipid enriched in early endosome membranes, and to phosphatidic acid. In contrast to TRPL, rhabdomeral localization of the membrane proteins Rh1 and TRP is not affected in the ttd14P75L mutant. The ttd14P75L mutation results in Rh1-independent photoreceptor degeneration and larval lethality suggesting that other processes are also affected by the ttd14P75L mutation. In conclusion, TTD14 is a novel regulator of TRPL trafficking, involved in internalization and subsequent sorting of TRPL into the recycling pathway that enables this ion channel to return to the plasma membrane

A Genetic Model to Study the Contribution of Brown and Brite Adipocytes to Metabolism

UCP1-dependent thermogenesis is studied to define new strategies to ameliorate obesity and type 2 diabetes; however, animal models are mostly limited to germline mutations of UCP1, which can effect adaptive changes in UCP1-independent pathways. We develop an inducible mouse model for the sequential ablation of UCP1+ brown and brite/beige adipocytes in adult mice. We demonstrate that activated brown adipocytes can increase systemic energy expenditure (EE) by 30%, while the contribution of brite/beige UCP1+ cells is <5%. Notably, UCP1+ adipocytes do not contribute to circulating FGF21 levels, either at room temperature or after cold exposure. We demonstrate that the FGF21-mediated effects on EE and glucose homeostasis are partially dependent on the presence of UCP1+ cells, while the effect on weight loss is not. In conclusion, acute UCP1+ cell deletion may be a useful model to study the impact of brown and brite/beige adipocytes on metabolism.ISSN:2666-3864ISSN:2211-124

Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP) is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production

Adenovirus E1A/E1B transformed amniotic fluid cells support human cytomegalovirus replication

The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP) is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production

Peripherin-2 differentially interacts with cone opsins in outer segments of cone photoreceptors

Peripherin-2 is a glycomembrane protein exclusively expressed in the light-sensing compartments of rod and cone photoreceptors designated as outer segments (OS). Mutations in peripherin-2 are associated with degenerative retinal diseases either affecting rod or cone photoreceptors. While peripherin-2 has been extensively studied in rods, there is only little information on its supramolecular organization and function in cones. Recently, we have demonstrated that peripherin-2 interacts with the light detector rhodopsin in OS of rods. It remains unclear, however, if peripherin-2 also binds to cone opsins. Here, using a combination of co-immunoprecipitation analyses, transmission electron microscopy (TEM)-based immunolabeling experiments, and quantitative fluorescence resonance energy transfer (FRET) measurements in cone OS of wild type mice, we demonstrate that peripherin-2 binds to both, S-opsin and M-opsin. However, FRET-based quantification of the respective interactions indicated significantly less stringent binding of peripherin-2 to S-opsin compared to its interaction with M-opsin. Subsequent TEM-studies also showed less co-localization of peripherin-2 and S-opsin in cone OS compared to peripherin-2 and M-opsin. Furthermore, quantitative FRET analysis in acutely isolated cone OS revealed that the cone degeneration-causing V268I mutation in peripherin-2 selectively reduced binding to M-opsin without affecting the peripherin-2 interaction to S-opsin or rhodopsin. The differential binding of peripherin-2 to cone opsins and the mutant-specific interference with the peripherin-2/M-opsin binding points to a novel role of peripherin-2 in cones and might contribute to understanding the differential penetrance of certain peripherin-2 mutations in rods and cones. Finally, our results provide a proof-of-principle for quantitative FRET measurements of protein-protein interactions in cone OS