Scanning Tunneling Spectroscopic Studies of the Low-Energy Quasiparticle Excitations in Cuprate Superconductors

We report scanning tunneling spectroscopic (STS) studies of the low-energy quasiparticle excitations of cuprate superconductors as a function of magnetic field and doping level. Our studies suggest that the origin of the pseudogap (PG) is associated with competing orders (COs), and that the occurrence (absence) of PG above the superconducting (SC) transition T_c is associated with a CO energy Δ_(CO) larger (smaller) than the SC gap Δ_(SC). Moreover, the spatial homogeneity of Δ_(SC) and Δ_(CO) depends on the type of disorder in different cuprates: For optimally and under-doped YBa_2Cu_3O_(7−δ) (Y-123), we find that Δ_(SC) < Δ_(CO) and that both Δ_(SC) and Δ(CO) exhibit long-range spatial homogeneity, in contrast to the highly inhomogeneous STS in Bi_2Sr_2CaCu_2O_(8+x) (Bi-2212). We attribute this contrast to the stoichiometric cations and ordered apical oxygen in Y-123, which differs from the non-stoichiometric Bi-to-Sr ratio in Bi-2212 with disordered Sr and apical oxygen in the SrO planes. For Ca-doped Y-123, the substitution of Y by Ca contributes to excess holes and disorder in the CuO_2 planes, giving rise to increasing inhomogeneity, decreasing Δ_(SC) and Δ_(CO), and a suppressed vortex-solid phase. For electron-type cuprate Sr_(0.9)La_(0.1)CuO_2 (La-112), the homogeneous Δ_(SC) and Δ_(CO) distributions may be attributed to stoichiometric cations and the absence of apical oxygen, with Δ_(CO) < Δ_(SC) revealed only inside the vortex cores. Finally, the vortex-core radius (ξ_(halo)) in electron-type cuprates is comparable to the SC coherence length ξ_(SC), whereas ξ_(halo) ∼ 10ξ_(SC) in hole-type cuprates, suggesting that ξ_(halo) may be correlated with the CO strength. The vortex-state irreversibility line in the magnetic field versus temperature phase diagram also reveals doping dependence, indicating the relevance of competing orders to vortex pinning

THE COLLISION SPECTRUM OF Lambda-COALESCENTS

$\Lambda$-coalescents model the evolution of a coalescing system in which any number of blocks randomly sampled from the whole may merge into a larger block. For the coalescent restricted to initially $n$ singletons we study the collision spectrum $(X_{n,k}:2\le k\le n)$, where $X_{n,k}$ counts, throughout the history of the process, the number of collisions involving exactly $k$ blocks. Our focus is on the large $n$ asymptotics of the joint distribution of the $X_{n,k}$'s, as well as on functional limits for the bulk of the spectrum for simple coalescents. Similarly to the previous studies of the total number of collisions, the asymptotics of the collision spectrum largely depends on the behaviour of the measure $\Lambda$ in the vicinity of $0$. In particular, for beta$(a,b)$-coalescents different types of limit distributions occur depending on whether $02$.Comment: 21 pages, submitte

Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis

Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6Chi monocytes in the brain than antibiotic-treated mice. Elimination of Ly6Chi monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6Chi monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6Chi monocytes

Comparative structural response of two steel bridges constructed 100 years apart

This paper presents a comparative numerical analysis of the structural behaviour and seismic performance of two existing steel bridges, the Infiernillo II Bridge and the Pinhao Bridge, one located in Mexico and the other in Portugal. The two bridges have similar general geometrical characteristics, but were constructed 100 years apart. Three-dimensional structural models of both bridges are developed and analysed for various load cases and several seismic conditions. The results of the comparative analysis between the two bridges are presented in terms of natural frequencies and corresponding vibration modes, maximum stresses in the structural elements and maximum displacements. The study is aimed at determining the influence of a 1 century period in material properties, transverse sections and expected behaviour of two quite similar bridges. In addition, the influence of the bearing conditions in the global response of the Pinhao Bridge was evaluated

LRRK2 secretion in exosomes is regulated by 14-3-3

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway. Here, we show that LRRK2 is released in extracellular microvesicles (i.e. exosomes) from cells that natively express LRRK2. LRRK2 localizes to collecting duct epithelial cells in the kidney that actively secrete exosomes into urine. Purified urinary exosomes contain LRRK2 protein that is both dimerized and phosphorylated. We provide a quantitative proteomic profile of 1673 proteins in urinary exosomes and find that known LRRK2 interactors including 14-3-3 are some of the most abundant exosome proteins. Disruption of the 14-3-3 LRRK2 interaction with a 14-3-3 inhibitor or through acute LRRK2 kinase inhibition potently blocks LRRK2 release in exosomes, but familial mutations in LRRK2 had no effect on secretion. LRRK2 levels were overall comparable but highly variable in urinary exosomes derived from PD cases and age-matched controls, although very high LRRK2 levels were detected in some PD affected cases. We further characterized LRRK2 exosome release in neurons and macrophages in culture, and found that LRRK2-positive exosomes circulate in cerebral spinal fluid (CSF). Together, these results define a pathway for LRRK2 extracellular release, clarify one function of the LRRK2 14-3-3 interaction and provide a foundation for utilization of LRRK2 as a biomarker in clinical trial

Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels

Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity

A Screen for Spore Wall Permeability Mutants Identifies a Secreted Protease Required for Proper Spore Wall Assembly

The ascospores of Saccharomyces cerevisiae are surrounded by a complex wall that protects the spores from environmental stresses. The outermost layer of the spore wall is composed of a polymer that contains the cross-linked amino acid dityrosine. This dityrosine layer is important for stress resistance of the spore. This work reports that the dityrosine layer acts as a barrier blocking the diffusion of soluble proteins out of the spore wall into the cytoplasm of the ascus. Diffusion of a fluorescent protein out of the spore wall was used as an assay to screen for mutants affecting spore wall permeability. One of the genes identified in this screen, OSW3 (RRT12/YCR045c), encodes a subtilisin-family protease localized to the spore wall. Mutation of the active site serine of Osw3 results in spores with permeable walls, indicating that the catalytic activity of Osw3 is necessary for proper construction of the dityrosine layer. These results indicate that dityrosine promotes stress resistance by acting as a protective shell around the spore. OSW3 and other OSW genes identified in this screen are strong candidates to encode enzymes involved in assembly of this protective dityrosine coat