Effects of disorder on Coulomb-assisted braiding of Majorana zero modes

Majorana zero modes in one-dimensional topological superconductors obey non-Abelian braiding statistics. Braiding manipulations can be realized by controlling Coulomb couplings in hybrid Majorana-transmon devices. However, strong disorder may induce accidental Majorana modes, which are expected to have detrimental effects on braiding statistics. Nevertheless, we show that the Coulomb-assisted braiding protocol is efficiently realized also in the presence of accidental modes. The errors occurring during the braiding cycle are small if the couplings of the computational Majorana modes to the accidental ones are much weaker than the maximum Coulomb coupling.Comment: 7 pages, 4 figures, this is the final, published versio

MicroRNA-276a Functions in Ellipsoid Body and Mushroom Body Neurons for Naive and Conditioned Olfactory Avoidance in Drosophila

MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development and function. But there are few cases in which the roles of individual miRNAs have been elucidated in behaving animals. We report a miR-276a::DopR regulatory module in Drosophila that functions in distinct circuits for naive odor responses and conditioned odor memory. Drosophila olfactory aversive memory involves convergence of the odors (conditioned stimulus) and the electric shock (unconditioned stimulus) in mushroom body (MB) neurons. Dopamine receptor DopR mediates the unconditioned stimulus inputs onto MB. Distinct dopaminergic neurons also innervate ellipsoid body (EB), where DopR function modulates arousal to external stimuli. We demonstrate that miR-276a is required in MB neurons for memory formation and in EB for naive responses to odors. Both roles of miR-276a are mediated by tuning DopR expression. The dual role of this miR-276a::DopR genetic module in these two neural circuits highlights the importance of miRNA-mediated gene regulation within distinct circuits underlying both naive behavioral responses and memory

Proteomic Identification of Protein Targets for 15-Deoxy-Δ12,14-Prostaglandin J2 in Neuronal Plasma Membrane

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D2 (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ2, respectively. Previously, we reported that the cytotoxicity of 15d-PGJ2 was independent of DP2 and PPARγ, and suggested that 15d-PGJ2 induced apoptosis through the novel specific binding sites of 15d-PGJ2 different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ2 to amyloidoses, we performed binding assay [3H]15d-PGJ2 and specified targets for 15d-PGJ2 associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ2 and fibrillar Aβ. Specific binding sites of [3H]15d-PGJ2 were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [3H]15d-PGJ2 were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ2 in the plasma membrane. By using biotinylated 15d-PGJ2, eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α), cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α). GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ2 plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues

FOXN1 forms higher-order nuclear condensates displaced by mutations causing immunodeficiency

The transcription factor FOXN1 is a master regulator of thymic epithelial cell (TEC) development and function. Here, we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multimolecular nuclear condensates essential for the factor’s transcriptional activity. FOXN1’s C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are altered in a patient with a mutant FOXN1 that is modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog selectively impairs mouse TEC differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect

MicroRNA-Related Cofilin Abnormality in Alzheimer's Disease

Rod-like structures composed of actin and the actin-binding protein cofilin are found in Alzheimer's disease (AD) patients. However, the mechanisms underlying formation of these structures and their pathological consequences are still largely unknown. We found that microRNAs 103 and 107 repress translation of cofilin, and that reduced levels of miR-103 or miR-107 are associated with elevated cofilin protein levels and formation of rod-like structures in a transgenic mouse model of AD. These results suggest that microRNAs may play an important role in cytoskeletal pathology in AD

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life

Engineering and manipulating topological qubits in 1D quantum wires

We investigate the Josephson effect in TNT and NTN junctions, consisting of topological (T) and normal (N) phases of semiconductor-superconductor 1D heterostructures in the presence of a Zeeman field. A key feature of our setup is that, in addition to the variation of the phase of the superconducting order parameter, we allow the orientation of the magnetic field to change along the junction. We find a novel magnetic contribution to the Majorana Josephson coupling that permits the Josephson current to be tuned by changing the orientation of the magnetic field along the junction. We also predict that a spin current can be generated by a finite superconducting phase difference, rendering these materials potential candidates for spintronic applications. Finally, this new type of coupling not only constitutes a unique fingerprint for the existence of Majorana bound states but also provides an alternative pathway for manipulating and braiding topological qubits in networks of wires.Comment: references and a note were added in v2; 6 pages, 2 figures; v1 had been submitted for the ICM2012 proceedings on the 31st of May 201

Transport in topological insulator nanowires

In this chapter we review our work on the theory of quantum transport in topological insulator nanowires. We discuss both normal state properties and superconducting proximity effects, including the effects of magnetic fields and disorder. Throughout we assume that the bulk is insulating and inert, and work with a surface-only theory. The essential transport properties are understood in terms of three special modes: in the normal state, half a flux quantum along the length of the wire induces a perfectly transmitted mode protected by an effective time reversal symmetry; a transverse magnetic field induces chiral modes at the sides of the wire, with different chiralities residing on different sides protecting them from backscattering; and, finally, Majorana zero modes are obtained at the ends of a wire in a proximity to a superconductor, when combined with a flux along the wire. Some parts of our discussion have a small overlap with the discussion in the review [Bardarson and Moore, Rep. Prog. Phys., 76, 056501, (2013)]. We do not aim to give a complete review of the published literature, instead the focus is mainly on our own and directly related work.Comment: 22 pages, 8 figures; Chapter in "Topological Matter. Springer Series in Solid-State Sciences, vol 190. Springer