Spontaneous edge currents for the Dirac equation in two space dimensions

Spontaneous edge currents are known to occur in systems of two space dimensions in a strong magnetic field. The latter creates chirality and determines the direction of the currents. Here we show that an analogous effect occurs in a field-free situation when time reversal symmetry is broken by the mass term of the Dirac equation in two space dimensions. On a half plane, one sees explicitly that the strength of the edge current is proportional to the difference between the chemical potentials at the edge and in the bulk, so that the effect is analogous to the Hall effect, but with an internal potential. The edge conductivity differs from the bulk (Hall) conductivity on the whole plane. This results from the dependence of the edge conductivity on the choice of a selfadjoint extension of the Dirac Hamiltonian. The invariance of the edge conductivity with respect to small perturbations is studied in this example by topological techniques.Comment: 10 pages; final versio

A human phospholipid phosphatase activated by a transmembrane control module

In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P(2). In the chimera, enzymatic activity is controlled by membrane potential via hVSP1\u27s endogenous phosphoinositide binding motif. These findings suggest that the endogenous VSD of hVSP1 is a control module that initiates signaling through the phosphatase domain and indicate a role for VSP-mediated phosphoinositide signaling in mammals

A versatile functional interaction between electrically silent K V subunits and K V 7 potassium channels

Voltage-gated K+ (KV) channels govern K+ ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KV channels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric KV2 channels. Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our findings demonstrate that KV cross-family interaction is much more versatile than previously thought—possibly serving nature to shape potassium conductance to the needs of individual cell types

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease

Background and aimsNon-O blood type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. MethodsRetrospective analysis comprising two cohorts: (I) "US" including all adult liver transplantations in the US in the MELD era and (II) "Vienna" comprising patients with a hepatic venous pressure gradient (HVPG) >= 6 mmHg. Results(I) The "US cohort" included 84 947 patients (non-O: 55.43%). The prevalence of PVT at the time of listing (4.37% vs 4.56%; P = .1762) and at liver transplantation (9.56% vs 9.33%; P = .2546) was similar in patients with O- and non-O-BT. (II) 411 patients were included in the "Vienna cohort" (non-O: 64%). Mean HVPG was 18(9) mmHg and 90% had an HVPG >= 10 mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)% vs 309(176)%; P = .048; increase of 23.8%-23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. ConclusionsAlthough non-O-BT impacts VWF in patients with early stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis

Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin

Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis

Background: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. Methods: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. Results: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78–10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01–8.03) and for late-onset cases, it was 5.48 (95% CI 4.10–7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. Conclusions: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy

Methods to Determine Neutrino Flux at Low Energies:Investigation of the Low ν\nu Method

We investigate the "low-$\nu$" method (developed by the CCFR/NUTEV collaborations) to determine the neutrino flux in a wide band neutrino beam at very low energies, a region of interest to neutrino oscillations experiments. Events with low hadronic final state energy $\nu<\nu_{cut}$ (of 1, 2 and 5 GeV) were used by the MINOS collaboration to determine the neutrino flux in their measurements of neutrino ($\nu_\mu$) and antineutrino (\nub_\mu) total cross sections. The lowest $\nu_\mu$ energy for which the method was used in MINOS is 3.5 GeV, and the lowest \nub_\mu energy is 6 GeV. At these energies, the cross sections are dominated by inelastic processes. We investigate the application of the method to determine the neutrino flux for $\nu_\mu$, \nub_\mu energies as low as 0.7 GeV where the cross sections are dominated by quasielastic scattering and $\Delta$(1232) resonance production. We find that the method can be extended to low energies by using $\nu_{cut}$ values of 0.25 and 0.50 GeV, which is feasible in fully active neutrino detectors such as MINERvA.Comment: 25 pages, 32 figures, to be published in European Physics Journal

“Dogged” Search of Fresh Nakhla Surfaces Reveals New Alteration Textures

Special Issue: 74th Annual Meeting of the Meteoritical Society, August 8-12, 2011, London, U.K.International audienceCarbonaceous chondrites are considered as amongst the most primitive Solar System samples available. One of their primitive characteristics is their enrichment in volatile elements.This includes hydrogen, which is present in hydrated and hydroxylated minerals. More precisely, the mineralogy is expected to be dominated by phyllosilicates in the case of CM chondrites, and by Montmorillonite type clays in the case of CI. Here, in order to characterize and quantify the abundance of lowtemperature minerals in carbonaceous chondrites, we performed thermogravimetric analysis of matrix fragments of Tagish Lake, Murchison and Orgueil