Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo: the first successful proof of principle in spontaneously hypertensive rats

Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and myocarditis, and have been increasingly seen as a treatment target. We recently identified an aptamer (single short DNA strand) that specifically binds and neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could be developed. Spontaneously hypertensive rats (SHR) positive for beta1(II)-AABs were treated five times at weekly intervals (bolus application of 2 mg/kg body weight followed by an infusion of the same amount over 20 min). SHR responded to aptamer treatment with a strong reduction in the cardio-pathogenic beta1(II)-AABs. The AABs did not substantially return within the study period. No signs for aptamer toxicity were observed by visual examination of the heart, liver, and kidney, or by measurement of plasma CK, ALT, and creatinine. The aptamer's potential for beta1(II)-AAB neutralization and consequently for cardiomyopathy treatment has been shown for the first time in vivo

Anomalous behavior of the electronic structure of Bi1 xInx 2Se3 across the quantum phase transition from topological to trivial insulator

Using spin- and angle-resolved photoemission spectroscopy and relativistic many-body calculations, we investigate the evolution of the electronic structure of (Bi1−xInx)2Se3 bulk single crystals around the critical point of the trivial to topological insulator quantum-phase transition. By increasing x, we observe how a surface gap opens at the Dirac point of the initially gapless topological surface state of Bi2Se3, leading to the existence of massive fermions. The surface gap monotonically increases for a wide range of x values across the topological and trivial sides of the quantum-phase transition. By means of photon-energy-dependent measurements, we demonstrate that the gapped surface state survives the inversion of the bulk bands which occurs at a critical point near x=0.055. The surface state exhibits a nonzero in-plane spin polarization which decays exponentially with increasing x, and which persists in both the topological and trivial insulator phases. Our calculations reveal qualitative agreement with the experimental results all across the quantum-phase transition upon the systematic variation of the spin-orbit coupling strength. A non-time-reversal symmetry-breaking mechanism of bulk-mediated scattering processes that increase with decreasing spin-orbit coupling strength is proposed as explanation

Mn rich MnSb2Te4 A topological insulator with magnetic gap closing at high Curie temperatures of 45 50 K

Ferromagnetic topological insulators exhibit the quantum anomalous Hall effect, which is potentially useful for high precision metrology, edge channel spintronics, and topological qubits. The stable 2 state of Mn enables intrinsic magnetic topological insulators. MnBi2Te4 is, however, antiferromagnetic with 25 K N el temperature and is strongly n doped. In this work, p type MnSb2Te4, previously considered topologically trivial, is shown to be a ferromagnetic topological insulator for a few percent Mn excess. i Ferromagnetic hysteresis with record Curie temperature of 45 50 K, ii out of plane magnetic anisotropy, iii a 2D Dirac cone with the Dirac point close to the Fermi level, iv out of plane spin polarization as revealed by photoelectron spectroscopy, and v a magnetically induced bandgap closing at the Curie temperature, demonstrated by scanning tunneling spectroscopy STS , are shown. Moreover, a critical exponent of the magnetization amp; 946; amp; 8776; 1 is found, indicating the vicinity of a quantum critical point. Ab initio calculations reveal that Mn Sb site exchange provides the ferromagnetic interlayer coupling and the slight excess of Mn nearly doubles the Curie temperature. Remaining deviations from the ferromagnetic order open the inverted bulk bandgap and render MnSb2Te4 a robust topological insulator and new benchmark for magnetic topological insulator

Large magnetic gap at the Dirac point in Bi2Te3/MnBi2Te4 heterostructures

Magnetically doped topological insulators enable the quantum anomalous Hall effect (QAHE), which provides quantized edge states for lossless charge-transport applications1,2,3,4,5,6,7,8. The edge states are hosted by a magnetic energy gap at the Dirac point2, but hitherto all attempts to observe this gap directly have been unsuccessful. Observing the gap is considered to be essential to overcoming the limitations of the QAHE, which so far occurs only at temperatures that are one to two orders of magnitude below the ferromagnetic Curie temperature, TC (ref. 8). Here we use low-temperature photoelectron spectroscopy to unambiguously reveal the magnetic gap of Mn-doped Bi2Te3, which displays ferromagnetic out-of-plane spin texture and opens up only below TC. Surprisingly, our analysis reveals large gap sizes at 1 kelvin of up to 90 millielectronvolts, which is five times larger than theoretically predicted9. Using multiscale analysis we show that this enhancement is due to a remarkable structure modification induced by Mn doping: instead of a disordered impurity system, a self-organized alternating sequence of MnBi2Te4 septuple and Bi2Te3 quintuple layers is formed. This enhances the wavefunction overlap and size of the magnetic gap10. Mn-doped Bi2Se3 (ref. 11) and Mn-doped Sb2Te3 form similar heterostructures, but for Bi2Se3 only a nonmagnetic gap is formed and the magnetization is in the surface plane. This is explained by the smaller spin–orbit interaction by comparison with Mn-doped Bi2Te3. Our findings provide insights that will be crucial in pushing lossless transport in topological insulators towards room-temperature applications