Additivity of relative magnetic helicity in finite volumes

CONTEXT: Relative magnetic helicity is conserved by magneto-hydrodynamic evolution even in the presence of moderate resistivity. For that reason, it is often invoked as the most relevant constraint on the dynamical evolution of plasmas in complex systems, such as solar and stellar dynamos, photospheric flux emergence, solar eruptions, and relaxation processes in laboratory plasmas. However, such studies often indirectly imply that relative magnetic helicity in a given spatial domain can be algebraically split into the helicity contributions of the composing subvolumes, in other words that it is an additive quantity. A limited number of very specific applications have shown that this is not the case. AIMS: Progress in understanding the nonadditivity of relative magnetic helicity requires removal of restrictive assumptions in favor of a general formalism that can be used in both theoretical investigations and numerical applications. METHODS: We derive the analytical gauge-invariant expression for the partition of relative magnetic helicity between contiguous finite volumes, without any assumptions on either the shape of the volumes and interface, or the employed gauge. RESULTS: We prove the nonadditivity of relative magnetic helicity in finite volumes in the most general, gauge-invariant formalism, and verify this numerically. We adopt more restrictive assumptions to derive known specific approximations, which yields a unified view of the additivity issue. As an example, the case of a flux rope embedded in a potential field shows that the nonadditivity term in the partition equation is, in general, non-negligible. CONCLUSIONS: The nonadditivity of relative magnetic helicity can potentially be a serious impediment to the application of relative helicity conservation as a constraint on the complex dynamics of magnetized plasmas. The relative helicity partition formula can be applied to numerical simulations to precisely quantify the effect of nonadditivity on global helicity budgets of complex physical processes

Microparticle-mediated VZV propagation and endothelial activation: Mechanism of VZV vasculopathy

OBJECTIVE: Varicella zoster virus (VZV) can spread anterogradely and infect cerebral arteries causing VZV vasculopathy and arterial ischemic stroke. In this study, we tested the hypothesis that virus-infected cerebrovascular fibroblasts undergo phenotypic changes that promote vascular remodeling and facilitate virus transmission in an in vitro model of VZV vasculopathy. The aims of this project were therefore to examine the changes that virus-infected human brain adventitial vascular fibroblasts (HBVAFs) undergo in an in vitro model of VZV vasculopathy and to identify disease biomarkers relating to VZV-related vasculopathy. METHODS: HBVAFs were infected with VZV, and their ability to migrate, proliferate, transdifferentiate, and interact with endothelial cells was studied with flow cytometry. Microparticles (MPs) released from these cells were isolated and imaged with transmission electron microscopy, and their protein content was analyzed with mass spectrometry. Circulating MP profiles were also studied in children with VZV and non-VZV vasculopathy and compared with controls. RESULTS: VZV-infected HBVAFs transdifferentiated into myofibroblasts with enhanced proliferative and migratory capacity. Interaction of VZV-infected HBVAFs with endothelial cells resulted in endothelial dysfunction. These effects were, in part, mediated by the release of MPs from VZV-infected HBVAFs. These MPs contained VZV virions that could transmit VZV to neighboring cells, highlighting a novel model of VZV cell-to-cell viral dissemination. MPs positive for VZV were significantly higher in children with VZV-related vasculopathy compared to children with non-VZV vasculopathy (p = 0.01) and controls (p = 0.007). CONCLUSIONS: VZV-infected HBVAFs promote vascular remodeling and facilitate virus transmission. These effects were mediated by the release of apoptotic MPs that could transmit VZV infection to neighboring cells through a Trojan horse means of productive viral infection. VZV+ MPs may represent a disease biomarker worthy of further study

Th17 cytokines disrupt the airway mucosal barrier in chronic rhinosinusitis

Cytokine mediated changes in paracellular permeability contribute to a multitude of pathological conditions including chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of interferons and of Th1, Th2, and Th17 cytokines on respiratory epithelium barrier function. Cytokines and interferons were applied to the basolateral side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS with nasal polyp patients. Transepithelial electrical resistance (TEER) and permeability of FITC-conjugated dextrans were measured over time. Additionally, the expression of the tight junction protein Zona Occludens-1 (ZO-1) was examined via immunofluorescence. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Our results showed that application of interferons and of Th1 or Th2 cytokines did not affect the mucosal barrier function. In contrast, the Th17 cytokines IL-17, IL-22, and IL-26 showed a significant disruption of the epithelial barrier, evidenced by a loss of TEER, increased paracellular permeability of FITC-dextrans, and discontinuous ZO-1 immunolocalisation. These results indicate that Th17 cytokines may contribute to the development of CRSwNP by promoting a leaky mucosal barrier.Mahnaz Ramezanpour, Sophia Moraitis, Jason L. P. Smith, P. J. Wormald, and Sarah Vreugd

In which shell-type SNRs should we look for gamma-rays and neutrinos from p-p collisions?

We present a simple analytic model for the various contributions to the non-thermal emission from shell type SNRs, and show that this model's results reproduce well the results of previous detailed calculations. We show that the \geq 1 TeV gamma ray emission from the shell type SNRs RX J1713.7-3946 and RX J0852.0-4622 is dominated by inverse-Compton scattering of CMB photons (and possibly infra-red ambient photons) by accelerated electrons. Pion decay (due to proton-proton collisions) is shown to account for only a small fraction, \lesssim10^-2, of the observed flux, as assuming a larger fractional contribution would imply nonthermal radio and X-ray synchrotron emission and thermal X-ray Bremsstrahlung emission that far exceed the observed radio and X-ray fluxes. Models where pion decay dominates the \geq 1 TeV flux avoid the implied excessive synchrotron emission (but not the implied excessive thermal X-ray Bremsstrahlung emission) by assuming an extremely low efficiency of electron acceleration, K_ep \lesssim 10^-4 (K_ep is the ratio of the number of accelerated electrons and the number of accelerated protons at a given energy). We argue that observations of SNRs in nearby galaxies imply a lower limit of K_ep \gtrsim 10^-3, and thus rule out K_ep values \lesssim 10^-4 (assuming that SNRs share a common typical value of K_ep). It is suggested that SNRs with strong thermal X-ray emission, rather than strong non-thermal X-ray emission, are more suitable candidates for searches of gamma rays and neutrinos resulting from proton-proton collisions. In particular, it is shown that the neutrino flux from the SNRs above is probably too low to be detected by current and planned neutrino observatories (Abridged).Comment: 13 pages, 1 figure, accepted for publication in JCAP, minor revision

Th17 Cytokines Disrupt the Airway Mucosal Barrier in Chronic Rhinosinusitis

Copyright © 2016 Mahnaz Ramezanpour et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Cytokine mediated changes in paracellular permeability contribute to a multitude of pathological conditions including chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of interferons and of Th1, Th2, and Th17 cytokines on respiratory epithelium barrier function. Cytokines and interferons were applied to the basolateral side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS with nasal polyp patients. Transepithelial electrical resistance (TEER) and permeability of FITC-conjugated dextrans were measured over time. Additionally, the expression of the tight junction protein Zona Occludens-1 (ZO-1) was examined via immunofluorescence. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Our results showed that application of interferons and of Th1 or Th2 cytokines did not affect the mucosal barrier function. In contrast, the Th17 cytokines IL-17, IL-22, and IL-26 showed a significant disruption of the epithelial barrier, evidenced by a loss of TEER, increased paracellular permeability of FITC-dextrans, and discontinuous ZO-1 immunolocalisation. These results indicate that Th17 cytokines may contribute to the development of CRSwNP by promoting a leaky mucosal barrier

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005–2021)

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required