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We demonstrate gate-tunable giant field-dependent nonreciprocal transport (magnetochiral anisotropy) in a noncentrosymmetric superconductor $T_{\rm d}$-MoTe$_2$ in the thin limit. Giant magnetochiral anisotropy (MCA) with a rectification coefficient $\gamma$ = $3.1 \times 10^6$ T$^{-1}$ A$^{-1}$, is observed at 230 mK, below the superconducting transition temperature ($T_c$). This is one of the largest values reported so far and is likely attributed to the reduced symmetry of the crystal structure. The temperature dependence of $\gamma$ indicates that the ratchet-like motion of magnetic vortices is the origin of the MCA, as supported by our theoretical model. For bilayer $T_{\rm d}$-MoTe$_2$, we successfully perform gate control of the MCA and realize threefold modulation of $\gamma$. Our experimental results provide a new route to realizing electrically controllable superconducting rectification devices in a single material., Comment: 7 pages, 3 figures

We report transport measurements of strained InAs/In$_{x}$Ga$_{1-x}$Sb composite quantum wells (CQWs) in the quantum spin Hall phase, focusing on the control of the energy gap through structural parameters and an external electric field. For highly strained CQWs with $x = 0.4$, we obtain a gap of 35 meV, an order of magnitude larger than that reported for binary InAs/GaSb CQWs. Using a dual-gate configuration, we demonstrate an electrical-field-driven topological phase transition, which manifests itself as a re-entrant behavior of the energy gap. The sizeable energy gap and high bulk resistivity obtained in both the topological and normal phases of a single device open the possibility of electrical switching of the edge transport., Comment: 5 pages, 4 figures

The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress. A key question is whether we can overcome these limitations and develop tools which are high-quality, reliable, easy to use and readily accessible for all investigators. Here, through chemical synthesis and studies of native and over-expressed channels by Ca(2+) and patch-clamp assays, we describe compound 31 (C31), a remarkable small-molecule inhibitor of TRPC1/4/5 channels. Its potency ranged from 9 to 1300 pM, depending on the TRPC1/4/5 subtype and activation mechanism. Other channel types investigated were unaffected, including TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8 and store-operated Ca(2+) entry mediated by Orai1. These findings suggest identification of an important experimental tool compound which has much higher potency for inhibiting TRPC1/4/5 channels than previously reported agents, impressive specificity, and graded subtype selectivity within the TRPC1/4/5 channel family. The compound should greatly facilitate future studies of these ion channels. We suggest naming this TRPC1/4/5-inhibitory compound Pico145.

BACKGROUND AND PURPOSE Transient receptor potential canonical 5 (TRPC5) channels are widely expressed, including in the CNS, where they potentiate fear responses. They also contribute to other non-selective cation channels that are stimulated by G-protein-coupled receptor agonists and lipid and redox factors. Steroids are known to modulate fear and anxiety states, and we therefore investigated whether TRPC5 exhibited sensitivity to steroids. EXPERIMENTAL APPROACH Human TRPC5 channels were conditionally expressed in HEK293 cells and studied using intracellular Ca2+ measurement, whole-cell voltage-clamp and excised patch techniques. For comparison, control experiments were performed with cells lacking TRPC5 channels or expressing another TRP channel, TRPM2. Native TRPC channel activity was recorded from vascular smooth muscle cells. KEY RESULTS Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity within 1–2 min. Dehydroepiandrosterone sulphate or 17β-oestradiol had weak inhibitory effects. Pregnenolone, and allopregnanolone, a progesterone metabolite and stereo-isomer of pregnanolone, all had no effects. Progesterone was the most potent of the steroids, especially against TRPC5 channel activity evoked by sphingosine-1-phosphate. In outside-out patch recordings, bath-applied progesterone and dihydrotestosterone had strong and reversible effects, suggesting relatively direct mechanisms of action. Progesterone inhibited native TRPC5-containing channel activity, evoked by oxidized phospholipid. CONCLUSIONS AND IMPLICATIONS Our data suggest that TRPC5 channels are susceptible to relatively direct and rapid stereo-selective steroid modulation, leading to channel inhibition. The study adds to growing appreciation of TRP channels as non-genomic steroid sensors.

© 2015 The Author(s).The caps on the ends of chromosomes, called telomeres, keep the ends of chromosomes from appearing as DNA double-strand breaks (DSBs) and prevent chromosome fusion. However, subtelomeric regions are sensitive to DSBs, which in normal c

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic1, 2, 3, 4, 5. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact6, 7, 8. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

Telomeres distinguish chromosome ends from double-strand breaks (DSBs) and prevent chromosome fusion. However, telomeres can also interfere with DNA repair, as shown by a deficiency in nonhomologous end joining (NHEJ) and an increase in large deletions at

Plasmons, which are collective charge oscillations, offer the potential to use optical signals in nano-scale electric circuits. Recently, plasmonics using graphene have attracted interest, particularly because of the tunable plasmon frequency through the carrier density $n$. However, the $n$ dependence of the plasmon velocity is weak ($\propto n^{1/4}$) and it is difficult to tune the frequency over orders of magnitude. Here, we demonstrate that the velocity of plasmons in graphene can be changed over two orders of magnitude by applying a magnetic field $B$ and by the presence/absence of a gate; at high $B$, edge magnetoplasmons (EMPs), which are plasmons localized at the sample edge, are formed and their velocity depends on $B$ and the gate screening effect. The wide range tunability of the velocity and the observed low-loss plasmon transport encourage designing graphene nanostructures for plasmonics applications., submitted

The transient receptor potential melastatin-3 (TRPM3) channel forms calcium-permeable, non-selective, cationic channels that are stimulated by pregnenolone sulphate (PregS). Here, we aimed to define chemical requirements of this acute steroid action and potentially reveal novel stimulators with physiological relevance.We used TRPM3 channels over-expressed in HEK 293 cells, with intracellular calcium measurement and whole-cell patch-clamp recording techniques.The stimulation of TRPM3 channels was confined to PregS and closely related steroids and not mimicked by other major classes of steroids, including progesterone. Relatively potent stimulation of TRPM3-dependent calcium entry was observed. A sulphate group positioned at ring A was important for strong stimulation but more striking was the requirement for a cis (beta) configuration of the side group, revealing previously unrecognized stereo-selectivity and supporting existence of a specific binding site. A cis-oriented side group on ring A was not the only feature necessary for high activity because loss of the double bond in ring B reduced potency and loss of the acetyl group at ring D reduced efficacy and potency. Weak steroid stimulators of TRPM3 channels inhibited effects of PregS, suggesting partial agonism. In silico screening of chemical libraries for non-steroid modulators of TRPM3 channels revealed the importance of the steroid backbone for stimulatory effects.Our data defined some of the chemical requirements for acute stimulation of TRPM3 channels by steroids, supporting the existence of a specific and unique steroid binding site. Epipregnanolone sulphate was identified as a novel TRPM3 channel stimulator.

XXVI International workshop on Condensed Matter Theories, 2002

We study the Zeeman splitting in induced ballistic 1D quantum wires aligned along the [233] and [011] axes of a high mobility (311)A undoped heterostructure. Our data shows that the g-factor anisotropy for magnetic fields applied along the high symmetry [011] direction can be explained by the 1D confinement only. However when the magnetic field is along [233] there is an interplay between the 1D confinement and 2D crystal anisotropy. This is highlighted for the [233] wire by an unusual non-monotonic behavior of the g-factor as the wire is made narrower.

Magneto-transport and drag measurements on a quasi-Corbino 2D electron bilayer at the systems total filling factor 1 (v_tot=1) reveal a drag voltage that is equal in magnitude to the drive voltage as soon as the two layers begin to form the expected v_tot=1 exciton condensate. The identity of both voltages remains present even at elevated temperatures of 0.25 K. The conductance in the current carrying layer vanishes only in the limit of strong coupling between the two layers and at T->0 K which suggests the presence of an excitonic circular current.

Throughout the body there are smooth muscle cells controlling a myriad of tubes and reservoirs. The cells show enormous diversity and complexity compounded by a plasticity that is critical in physiology and disease. Over the past quarter of a century we have seen that smooth muscle cells contain – as part of a gamut of ion-handling mechanisms – a family of cationic channels with significant permeability to calcium, potassium and sodium. Several of these channels are sensors of calcium store depletion, G-protein-coupled receptor activation, membrane stretch, intracellular Ca2+, pH, phospholipid signals and other factors. Progress in understanding the channels has, however, been hampered by a paucity of specific pharmacological agents and difficulty in identifying the underlying genes. In this review we summarize current knowledge of these smooth muscle cationic channels and evaluate the hypothesis that the underlying genes are homologues of Drosophila TRP (transient receptor potential). Direct evidence exists for roles of TRPC1, TRPC4/5, TRPC6, TRPV2, TRPP1 and TRPP2, and more are likely to be added soon. Some of these TRP proteins respond to a multiplicity of activation signals – promiscuity of gating that could enable a variety of context-dependent functions. We would seem to be witnessing the first phase of the molecular delineation of these cationic channels, something that should prove a leap forward for strategies aimed at developing new selective pharmacological agents and understanding the activation mechanisms and functions of these channels in physiological systems.

Periodic antidot arrays imposed upon two-dimensional hole systems (2DHSs) display a striking dependence of the positive low-field magnetoresistance on the in-plane crystallographic orientation of the superlattice. An enhanced positive magnetoresistance can be ascribed to the 2DHSs non-circular Fermi surface which stabilizes chaotic trajectories for specific crystallographic directions. The effect provides a first example of the role of non-spherical Fermi surfaces on the classical chaotic dynamics of charge carriers. Transport calculations taking into account both the classical chaotic motion of the holes in antidot lattices and the warped Fermi contour confirm this picture.

We measured the magnetoresistance of bilayer quantum Hall (QH) effects at the fractional filling factor $\nu =2/3$ by changing the total electron density and the density difference between two layers. Three different QH states were separated by two types of phase transition: One is the spin transition and the other is the pseudospin transition. In addition, two different hystereses were detected, one of which is specific to bilayer systems. The phase transitions and the hystereses are described well by a composite fermion model extended to a bilayer system., Comment: 4 pages, 5 figures

We measured the magnetoresistance of bilayer quantum Hall (QH) effects at the fractional filling factor $��=2/3$ by changing the total electron density and the density difference between two layers. Three different QH states were separated by two types of phase transition: One is the spin transition and the other is the pseudospin transition. In addition, two different hystereses were detected, one of which is specific to bilayer systems. The phase transitions and the hystereses are described well by a composite fermion model extended to a bilayer system., 4 pages, 5 figures

Physical Review Letters

By tilting the samples in the magnetic field, we measured and compared the Skyrmion excitations in the bilayer quantum Hall (QH) state at the Landau-level filling factor $��=2$ and in the monolayer QH state at $��=1$. The observed number of flipped spins is $N_s=14$ in the bilayer system with a large tunneling gap, and $N_s=7$ in the bilayer system with a small tunneling gap, while it is $N_s=7$ in the monolayer system. The difference is interpreted due to the interlayer exchange interaction. Moreover, we have observed seemingly preferred numbers $N_s=14,7,1$ for the flipped spins by tilting bilayer samples., 4 pages, 4 figures

Direct effects of ONO-1101 ¿(-)-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-[4-[(S) -2-hydroxy-3-(2-morpholino carbonylamino)ethylamino] propoxy]phenylpropionate monohydrochloride), a novel beta-antagonist, on action potential parameters and membrane currents, and its beta adrenoceptor antagonism were examined in cardiac muscle. Action potential-parameters in papillary muscle of reserpinized animals and membrane currents recorded from single myocytes obtained from guinea pig and rabbit hearts were not affected by 1 to 100 microM ONO-1101. On the other hand, ONO-1101 markedly inhibited the potentiation of Ca current by isoproterenol in single cardiac myocytes of the guinea pig. The concentration-response relationship of Ca current for isoproterenol was shifted to the right. This effect resembled that of esmolol, which is also a beta adrenoceptor antagonist. A Schild plot analysis revealed the slope and pA2 value of each antagonist (ONO-1101, 0.94, 8.0; and esmolol, 0.98, 7.3, respectively) and demonstrated that ONO-1101 is about 5 times more potent than esmolol as a beta-antagonist. Two other effects of isoproterenol: 1) potentiation of delayed rectifier K current and 2) activation of chloride current, were also inhibited by ONO-1101. The time required for 50% removal of beta-antagonism of ONO-1101 and esmolol after the washout was estimated as 4 and 6 min, respectively, in depolarized papillary muscle. These results suggest that ONO-1101 is a potent beta-antagonist whose effects were removed quickly by washout. When applied at what is thought to be a clinical dosage, ONO-1101 had no direct effects on action potential-parameters and membrane currents in cardiac muscle. These characteristics of ONO-1101 suggest that this agent may be effective in clinical use.