The role of the microbiome in driving RA-related autoimmunity

Once referred to as “normal commensal flora” the human microbiome plays an integral role between health and disease. The host mucosal surface replete with a multitude of immune cells is a vast arena constantly sensing and responding to antigen presentation and microbial by-products. It is this key role that may allow the microbiome to prime or protect the host from autoimmune disease. Rheumatoid arthritis (RA) is a chronic, disabling inflammatory condition characterized by a complex multifactorial etiology. The presence of certain genetic markers has been proven to increase susceptibility to RA however it does not guarantee disease development. Given low concordance rates demonstrated in monozygotic twin studies there is a clear implication for the involvement of external players in RA pathogenesis. Since the historical description of rheumatoid factor, numerous additional autoantibodies have been described in the sera of RA patients. The presence of anti-cyclic citrullinated protein antibody is now a standard test, and is associated with a more severe disease course. Interestingly these antibodies are detectable in patient’s sera long before the clinical signs of RA occur. The production of autoantibodies is driven by the lack of tolerance of the immune system, and how tolerance is broken is a crucial question for understanding RA development. Here we review current literature on the role of the microbiome in RA development including periodontal, gut and lung mucosa, with particular focus on proposed mechanisms of host microbiome interactions. We discuss the use of Mendelian randomization to assign causality to the microbiome and present considerations for future studies

Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium

© 2015 Webster et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Spontaneous time reversal symmetry breaking in the pseudogap state of high-Tc superconductors

When matter undergoes a phase transition from one state to another, usually a change in symmetry is observed, as some of the symmetries exhibited are said to be spontaneously broken. The superconducting phase transition in the underdoped high-Tc superconductors is rather unusual, in that it is not a mean-field transition as other superconducting transitions are. Instead, it is observed that a pseudo-gap in the electronic excitation spectrum appears at temperatures T* higher than Tc, while phase coherence, and superconductivity, are established at Tc (Refs. 1, 2). One would then wish to understand if T* is just a crossover, controlled by fluctuations in order which will set in at the lower Tc (Refs. 3, 4), or whether some symmetry is spontaneously broken at T* (Refs. 5-10). Here, using angle-resolved photoemission with circularly polarized light, we find that, in the pseudogap state, left-circularly polarized photons give a different photocurrent than right-circularly polarized photons, and therefore the state below T* is rather unusual, in that it breaks time reversal symmetry11. This observation of a phase transition at T* provides the answer to a major mystery of the phase diagram of the cuprates. The appearance of the anomalies below T* must be related to the order parameter that sets in at this characteristic temperature .Comment: 11 pages, 4 figure

Spitzer Observations of Interstellar Object 1I/`Oumuamua

1I/`Oumuamua is the first confirmed interstellar body in our Solar System. Here we report on observations of `Oumuamua made with the Spitzer Space Telescope on 2017 November 21--22 (UT). We integrated for 30.2~hours at 4.5 micron (IRAC channel 2). We did not detect the object and place an upper limit on the flux of 0.3 uJy (3sigma). This implies an effective spherical diameter less than [98, 140, 440] meters and albedo greater than [0.2, 0.1, 0.01] under the assumption of low, middle, or high thermal beaming parameter eta, respectively. With an aspect ratio for `Oumuamua of 6:1, these results correspond to dimensions of [240:40, 341:57, 1080:180] meters, respectively. We place upper limits on the amount of dust, CO, and CO2 coming from this object that are lower than previous results; we are unable to constrain the production of other gas species. Both our size and outgassing limits are important because `Oumuamua's trajectory shows non-gravitational accelerations that are sensitive to size and mass and presumably caused by gas emission. We suggest that `Oumuamua may have experienced low-level post-perihelion volatile emission that produced a fresh, bright, icy mantle. This model is consistent with the expected eta value and implied high albedo value for this solution, but, given our strict limits on CO and CO2, requires another gas species --- probably H2O --- to explain the observed non-gravitational acceleration. Our results extend the mystery of `Oumuamua's origin and evolution

An explanation for a universality of transition temperatures in families of copper oxide superconductors

A remarkable mystery of the copper oxide high-transition-temperature (Tc) superconductors is the dependence of Tc on the number of CuO2 layers, n, in the unit cell of a crystal. In a given family of these superconductors, Tc rises with the number of layers, reaching a peak at n=3, and then declines: the result is a bell-shaped curve. Despite the ubiquity of this phenomenon, it is still poorly understood and attention has instead been mainly focused on the properties of a single CuO2 plane. Here we show that the quantum tunnelling of Cooper pairs between the layers simply and naturally explains the experimental results, when combined with the recently quantified charge imbalance of the layers and the latest notion of a competing order nucleated by this charge imbalance that suppresses superconductivity. We calculate the bell-shaped curve and show that, if materials can be engineered so as to minimize the charge imbalance as n increases, Tc can be raised further.Comment: 15 pages, 3 figures. The version published in Natur

Imaging the Two Gaps of the High-TC Superconductor Pb-Bi2Sr2CuO6+x

The nature of the pseudogap state, observed above the superconducting transition temperature TC in many high temperature superconductors, is the center of much debate. Recently, this discussion has focused on the number of energy gaps in these materials. Some experiments indicate a single energy gap, implying that the pseudogap is a precursor state. Others indicate two, suggesting that it is a competing or coexisting phase. Here we report on temperature dependent scanning tunneling spectroscopy of Pb-Bi2Sr2CuO6+x. We have found a new, narrow, homogeneous gap that vanishes near TC, superimposed on the typically observed, inhomogeneous, broad gap, which is only weakly temperature dependent. These results not only support the two gap picture, but also explain previously troubling differences between scanning tunneling microscopy and other experimental measurements.Comment: 6 page

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Direct evidence for a competition between the pseudogap and high temperature superconductivity in the cuprates

A pairing gap and coherence are the two hallmarks of superconductivity. In a classical BCS superconductor they are established simultaneously at Tc. In the cuprates, however, an energy gap (pseudogap) extends above Tc. The origin of this gap is one of the central issues in high temperature superconductivity. Recent experimental evidence demonstrates that the pseudogap and the superconducting gap are associated with different energy scales. It is however not clear whether they coexist independently or compete. In order to understand the physics of cuprates and improve their superconducting properties it is vital to determine whether the pseudogap is friend or foe of high temperature supercondctivity. Here we report evidence from angle resolved photoemission spectroscopy (ARPES) that the pseudogap and high temperature superconductivity represent two competing orders. We find that there is a direct correlation between a loss in the low energy spectral weight due to the pseudogap and a decrease of the coherent fraction of paired electrons. Therefore, the pseudogap competes with the superconductivity by depleting the spectral weight available for pairing in the region of momentum space where the superconducting gap is largest. This leads to a very unusual state in the underdoped cuprates, where only part of the Fermi surface develops coherence.Comment: Improved version was published in Natur