569 research outputs found

    The ciliary machinery is repurposed for T cell immune synapse trafficking of LCK

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    Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a “regulatory arm” by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse

    Quantum Oscillations in the Underdoped Cuprate YBa2Cu4O8

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    We report the observation of quantum oscillations in the underdoped cuprate superconductor YBa2Cu4O8 using a tunnel-diode oscillator technique in pulsed magnetic fields up to 85T. There is a clear signal, periodic in inverse field, with frequency 660+/-15T and possible evidence for the presence of two components of slightly different frequency. The quasiparticle mass is m*=3.0+/-0.3m_e. In conjunction with the results of Doiron-Leyraud et al. for YBa2Cu3O6.5, the present measurements suggest that Fermi surface pockets are a general feature of underdoped copper oxide planes and provide information about the doping dependence of the Fermi surface.Comment: Contains revisions addressing referees' comments including a different Fig 1b. 4 pages, 4 figure

    Importance of adequate sample sizes in fatty acid intervention trials

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    Abstract not availableLisa N. Yelland, Maria Makrides, Andrew J. McPhee, Julie Quinlivan, Robert A. Gibso

    Developing a tool for obtaining maternal skinfold thickness measurements and assessing inter-observer variability among pregnant women who are overweight and obese

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    Extent: 6p.Background: It is estimated that between 34% and 50% of Australian women entering pregnancy are overweight and obese, which is associated with an increased risk in complications for both the woman and her infant. Current tools used in clinical and research practice for measuring body composition include body mass index (BMI), waist circumference and bioimpedance analysis. Not all of these measures are applicable for use during pregnancy due to a lack of differentiation between maternal and fetal contributions. While skinfold thickness measurement (SFTM) is increasingly being used in pregnancy, there is limited data and a lack of a standard tool for its use in overweight and obese pregnant women. Methods: We developed a standard tool for evaluating SFTM among women with a BMI ≥ 25 kg/m2. Forty-nine women were measured as part of a prospective cohort study nested within a multicentre randomised controlled trial (The LIMIT Randomised Controlled Trial). Two blinded observers each performed 2 skinfold measurements on the biceps, triceps and subscapular of each woman. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were used to analyse SFTM, body fat percentage (BF%) and inter-observer variability. Results: The ICC for inter-observer variability in measurements were considered moderate for biceps SFTM (ICC = 0.56) and triceps SFTM (ICC = 0.51); good for subscapular SFTM (ICC = 0.71) and BF% (ICC = 0.74); and excellent for arm circumference (ICC = 0.97). The standard error of measurements ranged from 0.53 cm for arm circumference to 3.58 mm for the subscapular SFTM. Conclusion: Our findings indicate that arm circumference and biceps, triceps and subscapular SFTM can be reliably obtained from overweight and obese pregnant women to calculate BF%, using multiple observers, and can be used in a research setting.Lavern M Kannieappan, Andrea R Deussen, Rosalie M Grivell, Lisa Yelland and Jodie M Dod

    Low-Frequency Quantum Oscillations due to Strong Electron Correlations

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    The normal-state energy spectrum of the two-dimensional tt-JJ model in a homogeneous perpendicular magnetic field is investigated. The density of states at the Fermi level as a function of the inverse magnetic field 1B\frac{1}{B} reveals oscillations in the range of hole concentrations 0.08<x<0.180.08<x<0.18. The oscillations have both high- and low-frequency components. The former components are connected with large Fermi surfaces, while the latter with van Hove singularities in the Landau subbands, which traverse the Fermi level with changing BB. The singularities are related to bending the Landau subbands due to strong electron correlations. Frequencies of these components are of the same order of magnitude as quantum oscillation frequencies observed in underdoped cuprates.Comment: 10 pages, 3 figures, Proc. NSS-2013, Yalta. arXiv admin note: text overlap with arXiv:1308.056

    Plasma oxylipins and unesterified precursor fatty acids are altered by DHA supplementation in pregnancy: Can they help predict risk of preterm birth?

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    Oxidized lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids, collectively known as oxylipins, are bioactive signaling molecules that play diverse roles in human health and disease. Supplementation with n-3 docosahexaenoic acid (DHA) during pregnancy has been reported to decrease the risk of preterm birth in singleton pregnancies, which may be due to effects of DHA supplementation on oxylipins or their precursor n-6 and n-3 fatty acids. There is only limited understanding of the levels and trajectory of changes in plasma oxylipins during pregnancy, effects of DHA supplementation on oxylipins and unesterified fatty acids, and whether and how oxylipins and their unesterified precursor fatty acids influence preterm birth. In the present study we used liquid chromatography-tandem mass spectrometry to profile oxylipins and their precursor fatty acids in the unesterified pool using plasma samples collected from a subset of pregnant Australian women who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) study. ORIP is a large randomized controlled trial testing whether daily supplementation with n-3 DHA can reduce the incidence of early preterm birth compared to control. Plasma was collected at study entry (≈pregnancy week 14) and again at ≈week 24, in a subgroup of 48 ORIP participants-12 cases with spontaneous preterm (&lt;37 weeks) birth and 36 matched controls with spontaneous term (≥40 weeks) birth. In the combined preterm and term pregnancies, we observed that in the control group without DHA supplementation unesterified AA and AA-derived oxylipins 12-HETE, 15-HETE and TXB2 declined between weeks 14-24 of pregnancy. Compared to control, DHA supplementation increased unesterified DHA, EPA, and AA, DHA-derived 4-HDHA, 10-HDHA and 19,20-EpDPA, and AA-derived 12-HETE at 24 weeks. In exploratory analysis independent of DHA supplementation, participants with concentrations above the median for 5-lipoxygenase derivatives of AA (5-HETE, Odds Ratio (OR) 8.2; p = 0.014) or DHA (4-HDHA, OR 8.0; p = 0.015) at 14 weeks, or unesterified AA (OR 5.1; p = 0.038) at 24 weeks had higher risk of spontaneous preterm birth. The hypothesis that 5-lipoxygenase-derived oxylipins and unesterified AA could serve as mechanism-based biomarkers predicting spontaneous preterm birth should be evaluated in larger, adequately powered studies

    de Haas-van Alphen effect investigations of the electronic structure of pure and aluminum-doped MgB_2

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    Understanding the superconducting properties of MgB_2 is based strongly on knowledge of its electronic structure. In this paper we review experimental measurements of the Fermi surface parameters of pure and Al-doped MgB_2 using the de Haas-van Alphen (dHvA) effect. In general, the measurements are in excellent agreement with the theoretical predictions of the electronic structure, including the strength of the electron-phonon coupling on each Fermi surface sheet. For the Al doped samples, we are able to measure how the band structure changes with doping and again these are in excellent agreement with calculations based on the virtual crystal approximation. We also review work on the dHvA effect in the superconducting state.Comment: Contribution to the special issue of Physica C "Superconductivity in MgB2: Physics and Applications" (10 Pages with figures
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