Unraveling the Nature of Charge Excitations in La2_2CuO4_4 with Momentum-Resolved Cu KK-edge Resonant Inelastic X-ray Scattering

Results of model calculations using exact diagonalization reveal the orbital character of states associated with different Raman loss peaks in Cu $K$-edge resonant inelastic X-ray scattering (RIXS) from La$_{2}$CuO$_{4}$. The model includes electronic orbitals necessary to highlight non-local Zhang-Rice singlet, charge transfer and $d$-$d$ excitations, as well as states with apical oxygen 2$p_z$ character. The dispersion of these excitations is discussed with prospects for resonant final state wave-function mapping. A good agreement with experiments emphasizes the substantial multi-orbital character of RIXS profiles in the energy transfer range 1-6 eV.Comment: Original: 4.5 pages. Replaced: 4 pages and 4 figures with updated content and reference

A comparison of vas occlusion techniques: cautery more effective than ligation and excision with fascial interposition

BACKGROUND: Vasectomy techniques have been the subject of relatively few rigorous studies. The objective of this analysis was to compare the effectiveness of two techniques for vas occlusion: intraluminal cautery versus ligation and excision with fascial interposition. More specifically, we aimed to compare early failure rates, sperm concentrations, and time to success between the two techniques. METHODS: We compared semen analysis data from men following vasectomy using two occlusion techniques. Data on intraluminal cautery came from a prospective observational study conducted at four sites. Data on ligation and excision with fascial interposition came from a multicenter randomized controlled trial that evaluated the efficacy of ligation and excision with versus without fascial interposition. The surgical techniques used in the fascial interposition study were standardized. The surgeons in the cautery study used their customary techniques, which varied among sites in terms of type of cautery, use of fascial interposition, excision of a short segment of the vas, and use of an open-ended technique. Men in both studies had semen analyses two weeks after vasectomy and then approximately every four weeks. The two outcome measures for the analyses presented here are (a) time to success, defined as severe oligozoospermia, or <100,000 sperm/mL in two consecutive semen analyses; and (b) early vasectomy failure, defined as >10 million sperm/mL at week 12 or later. RESULTS: Vasectomy with cautery was associated with a significantly more rapid progression to severe oligozoospermia and with significantly fewer early failures (1% versus 5%). CONCLUSION: The use of cautery improves vasectomy outcomes. Limitations of this comparison include (a) the variety of surgical techniques in the cautery study and differences in methods of fascial interposition between the two studies, (b) the uncertain correlation between sperm concentrations after vasectomy and the risk of pregnancy, and (c) the use of historical controls and different study sites

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules

Ascorbate Biosynthesis during Early Fruit Development Is the Main Reason for Its Accumulation in Kiwi

Background: Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. Methodology/Principal Findings: We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in large

Cosmological constraints from lensing statistics and supernovae on the cosmic equation of state

We investigate observational constraints from lensing statistics and high-z type Ia supernovae on flat cosmological models with nonrelativistic matter and an exotic fluid with equation of state, $p_x=(m/3 -1)\rho_x$. We show that agreement with both tests at the 68% confidence level is possible if the parameter $m$ is low ($m \lesssim 0.85$) and $0.24 \lesssim \Omega_{m0} \lesssim 0.38$ with lower values of $\Omega_{m0}$ corresponding to higher $m$. We find that a conventional cosmological constant model with $\Omega_{m0}\simeq 0.33$ is the best fit model of the combined likelihood.Comment: 7 pages, 4 postscript figures, revtex, submitted to Phys. Rev.

Immunomodulatory streptococci that inhibit CXCL8 secretion and NFκB activation are common members of the oral microbiota

Introduction. Oral tissues are generally homeostatic despite exposure to many potential inflammatory agents including the resident microbiota. This requires the balancing of inflammation by regulatory mechanisms and/or anti-inflammatory commensal bacteria. Thus, the levels of anti-inflammatory commensal bacteria in resident populations may be critical in maintaining this homeostatic balance. Hypothesis/Gap Statement. The incidence of immunosuppressive streptococci in the oral cavity is not well established. Determining the proportion of these organisms and the mechanisms involved may help to understand host-microbe homeostasis and inform development of probiotics or prebiotics in the maintenance of oral health. Aim. To determine the incidence and potential modes of action of immunosuppressive capacity in resident oral streptococci. Methodology. Supragingival plaque was collected from five healthy participants and supragingival and subgingival plaque from five with gingivitis. Twenty streptococci from each sample were co-cultured with epithelial cells±flagellin or LL-37. CXCL8 secretion was detected by ELISA, induction of cytotoxicity in human epithelial cells by lactate dehydrogenase release and NFκB-activation using a reporter cell line. Bacterial identification was achieved through partial 16S rRNA gene sequencing and next-generation sequencing. Results. CXCL8 secretion was inhibited by 94/300 isolates. Immunosuppressive isolates were detected in supragingival plaque from healthy (4/5) and gingivitis (4/5) samples, and in 2/5 subgingival (gingivitis) plaque samples. Most were Streptococcus mitis/oralis. Seventeen representative immunosuppressive isolates all inhibited NFκB activation. The immunosuppressive mechanism was strain specific, often mediated by ultra-violet light-labile factors, whilst bacterial viability was essential in certain species. Conclusion. Many streptococci isolated from plaque suppressed epithelial cell CXCL8 secretion, via inhibition of NFκB. This phenomenon may play an important role in oral host-microbe homeostasis

A study of halo and relic radio emission in merging clusters using the Murchison Widefield Array

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2017 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.We have studied radio haloes and relics in nine merging galaxy clusters using the Murchison Widefield Array (MWA). The images used for this study were obtained from the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey which was carried out at 5 frequencies, viz. 88, 118, 154, 188 and 215 MHz. We detect diffuse radio emission in 8 of these clusters. We have estimated the spectra of haloes and relics in these clusters over the frequency range 80-1400 MHz; the first such attempt to estimate their spectra at low frequencies. The spectra follow a power law with a mean value of $\alpha = -1.13\pm0.21$ for haloes and $\alpha = -1.2\pm0.19$ for relics where, $S \propto \nu^{\alpha}$. We reclassify two of the cluster sources as radio galaxies. The low frequency spectra are thus an independent means of confirming the nature of cluster sources. Five of the nine clusters host radio haloes. For the remaining four clusters, we place upper limits on the radio powers of possible haloes in them. These upper limits are a factor of 2-20 below those expected from the $L_{\rm X}-P_{\rm 1.4}$ relation. These limits are the lowest ever obtained and the implications of these limits to the hadronic model of halo emission are discussed.Peer reviewedFinal Published versio

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Monitoring Keap1-Nrf2 interactions in single live cells

AbstractThe transcription factor NF-E2 p45-related factor 2 (Nrf2) and its negative regulator Kelch-like ECH associated protein 1 (Keap1) control the expression of nearly 500 genes with diverse cytoprotective functions. Keap1, a substrate adaptor protein for Cullin3/Rbx1 ubiquitin ligase, normally continuously targets Nrf2 for degradation, but loses this ability in response to electrophiles and oxidants (termed inducers). Consequently, Nrf2 accumulates and activates transcription of its downstream target genes. Many inducers are phytochemicals, and cruciferous vegetables represent one of the richest sources of inducer activity among the most commonly used edible plants. Here we summarize the discovery of the isothiocyanate sulforaphane as a potent inducer which reacts with cysteine sensors of Keap1, leading to activation of Nrf2. We then describe the development of a quantitative Förster resonance energy transfer (FRET)-based methodology combined with multiphoton fluorescence lifetime imaging microscopy (FLIM) to investigate the interactions between Keap1 and Nrf2 in single live cells, and the effect of sulforaphane, and other cysteine-reactive inducers, on the dynamics of the Keap1–Nrf2 protein complex. We present the experimental evidence for the “cyclic sequential attachment and regeneration” or “conformation cycling” model of Keap1-mediated Nrf2 degradation. Finally, we discuss the implications of this mode of regulation of Nrf2 for achieving a fine balance under normal physiological conditions, and the consequences and mechanisms of disrupting this balance for tumor biology