SUPPRESSION of ELECTRON THERMAL CONDUCTION in the HIGH β INTRACLUSTER MEDIUM of GALAXY CLUSTERS

Understanding the thermodynamic state of the hot intracluster medium (ICM) in a galaxy cluster requires knowledge of the plasma transport processes, especially thermal conduction. The basic physics of thermal conduction in plasmas with ICM-like conditions has yet to be elucidated, however. We use particle-in-cell simulations and analytic models to explore the dynamics of an ICM-like plasma (with small gyroradius, large mean free path, and strongly sub-dominant magnetic pressure) driven by the diffusive heat flux associated with thermal conduction. Linear theory reveals that whistler waves are driven unstable by electron heat flux, even when the heat flux is weak. The resonant interaction of electrons with these waves then plays a critical role in scattering electrons and suppressing the heat flux. In a 1D model where only whistler modes that are parallel to the magnetic field are captured, the only resonant electrons are moving in the opposite direction to the heat flux, and the electron heat flux suppression is small. In 2D or more, oblique whistler modes also resonate with electrons moving in the direction of the heat flux. The overlap of resonances leads to effective symmetrization of the electron distribution function and a strong suppression of heat flux. The results suggest that thermal conduction in the ICM might be strongly suppressed, possibly to negligible levels

WRAP53 promotes cancer cell survival and is a potential target for cancer therapy

We previously identified WRAP53 as an antisense transcript that regulates the p53 tumor suppressor. The WRAP53 gene also encodes a protein essential for Cajal body formation and involved in cellular trafficking of the survival of motor neuron complex, the telomerase enzyme and small Cajal body-specific RNAs to Cajal bodies. Here, we show that the WRAP53 protein is overexpressed in a variety of cancer cell lines of different origin and that WRAP53 overexpression promotes cellular transformation. Knockdown of the WRAP53 protein triggers massive apoptosis through the mitochondrial pathway, as demonstrated by Bax/Bak activation, loss of mitochondrial membrane potential and cytochrome c release. The apoptosis induced by WRAP53 knockdown could moreover be blocked by Bcl-2 overexpression. Interestingly, human tumor cells are more sensitive to WRAP53 depletion as compared with normal human cells indicating that cancer cells in particular depends on WRAP53 expression for their survival. In agreement with this, we found that high levels of WRAP53 correlate with poor prognosis of head and neck cancer. Together these observations propose a role of WRAP53 in carcinogenesis and identify WRAP53 as a novel molecular target for a large fraction of malignancies

Critical gradient turbulence optimization toward a compact stellarator reactor concept

Integrating turbulence into stellarator optimization is shown by targeting the onset for the ion-temperature-gradient mode, highlighting effects of parallel connection length, local magnetic shear, and flux surface expansion. The result is a compact quasihelically symmetric stellarator configuration, admitting a set of uncomplicated coils, with significantly reduced turbulent heat fluxes compared to a known stellarator. The new configuration combines low values of neoclassical transport, good alpha particle confinement, and Mercier stability at a plasma beta of almost 2$\%$.Comment: 5 pages, 5 figures. Phys. Rev. Research 5, L032030 (2023

Suppression of Electron Thermal Conduction by Whistler Turbulence in a Sustained Thermal Gradient.

The dynamics of weakly magnetized collisionless plasmas in the presence of an imposed temperature gradient along an ambient magnetic field is explored with particle-in-cell simulations and modeling. Two thermal reservoirs at different temperatures drive an electron heat flux that destabilizes off-angle whistler-type modes. The whistlers grow to large amplitude, δB/B_{0}≃1, and resonantly scatter the electrons, significantly reducing the heat flux. Surprisingly, the resulting steady-state heat flux is largely independent of the thermal gradient. The rate of thermal conduction is instead controlled by the finite propagation speed of the whistlers, which act as mobile scattering centers that convect the thermal energy of the hot reservoir. The results are relevant to thermal transport in high-β astrophysical plasmas such as hot accretion flows and the intracluster medium of galaxy clusters

Adding value? A review of the international literature on the role of higher education in police training and education

This paper reviews the current English-language literature on developments in police training and education in order to identify common areas where higher education ‘adds value’ to police learning and development. Reforms in training and education are constituent parts of the ongoing shift to a service-oriented professional police in a number of countries. A comparative analysis of the literature on police training and education is provided here which focuses primarily on the USA, the European Union, Australia and India. The review provides a contribution to international policy debates about future developments in this area

Role of endolysosomes in HIV-1 Tat-induced neurotoxicity

Combined anti-retroviral therapeutic drugs effectively increase the lifespan of HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1 associated neurocognitive disorder). Soluble factors including HIV-1 proteins released from HIV-1-infected cells have been implicated in the pathogenesis of HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of transcription) protein because of its ability to directly excite neurons and cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated endocytosis and since endolysosomes play an important role in neuronal cell life and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is associated with changes in the endolysosome structure and function and also autophagy. Following the treatment of primary cultured rat hippocampal neurons with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was determined using a triple staining method. Preceding observations of HIV-1 Tat-induced neuronal cell death, we observed statistically significant changes in the structure and membrane integrity of endolysosomes, endolysosome pH and autophagy. As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in endolysosomes, endolysosome morphology was affected and their size increased, endolysosome membrane integrity was disrupted, endolysosome pH increased, specific activities of endolysosome enzymes decreased and autophagy was inhibited, as indicated by the significant changes in three markers for autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our findings suggest that endolysosomes are involved in HIV-1 Tat-induced neurotoxicity and may represent a target for therapeutic intervention against HAND

Inhaled corticosteroid use is associated with increased circulating tregulatory cells in children with asthma

BACKGROUND: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency

Depletion of Kinesin 5B Affects Lysosomal Distribution and Stability and Induces Peri-Nuclear Accumulation of Autophagosomes in Cancer Cells

Background: Enhanced lysosomal trafficking is associated with metastatic cancer. In an attempt to discover cancer relevant lysosomal motor proteins, we compared the lysosomal proteomes from parental MCF-7 breast cancer cells with those from highly invasive MCF-7 cells that express an active form of the ErbB2 (DN-ErbB2). Methodology/Principal Findings: Mass spectrometry analysis identified kinesin heavy chain protein KIF5B as the only microtubule motor associated with the lysosomes in MCF-7 cells, and ectopic DN-ErbB2 enhanced its lysosomal association. KIF5B associated with lysosomes also in HeLa cervix carcinoma cells as analyzed by subcellular fractionation. The depletion of KIF5B triggered peripheral aggregations of lysosomes followed by lysosomal destabilization, and cell death in HeLa cells. Lysosomal exocytosis in response to plasma membrane damage as well as fluid phase endocytosis functioned, however, normally in these cells. Both HeLa and MCF-7 cells appeared to express similar levels of the KIF5B isoform but the death phenotype was weaker in KIF5B-depleted MCF-7 cells. Surprisingly, KIF5B depletion inhibited the rapamycin-induced accumulation of autophagosomes in MCF-7 cells. In KIF5B-depleted cells the autophagosomes formed and accumulated in the close proximity to the Golgi apparatus, whereas in the control cells they appeared uniformly distributed in the cytoplasm. Conclusions/Significance: Our data identify KIF5B as a cancer relevant lysosomal motor protein with additional functions in autophagosome formatio