Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Field induced ordering in highly frustrated antiferromagnets

We predict that an external field can induce a spin order in highly frustrated classical Heisenberg magnets. We find analytically stabilization of collinear states by thermal fluctuations at a one-third of the saturation field for kagome and garnet lattices and at a half of the saturation field for pyrochlore and frustrated square lattices. This effect is studied numerically for the frustrated square-lattice antiferromagnet by Monte Carlo simulations for classical spins and by exact diagonalization for $S=1/2$. The field induced collinear states have a spin gap and produce magnetization plateaus.Comment: 4 pages, new analytical proof the order by disorder by thermal fluctuations is adde

The quiet crossing of ocean tipping points

Anthropogenic climate change profoundly alters the ocean’s environmental conditions, which, in turn, impact marine ecosystems. Some of these changes are happening fast and may be difficult to reverse. The identification and monitoring of such changes, which also includes tipping points, is an ongoing and emerging research effort. Prevention of negative impacts requires mitigation efforts based on feasible research-based pathways. Climate-induced tipping points are traditionally associated with singular catastrophic events (relative to natural variations) of dramatic negative impact. High-probability high-impact ocean tipping points due to warming, ocean acidification, and deoxygenation may be more fragmented both regionally and in time but add up to global dimensions. These tipping points in combination with gradual changes need to be addressed as seriously as singular catastrophic events in order to prevent the cumulative and often compounding negative societal and Earth system impacts

Field induced transitions in a kagome antiferromagnet

The thermal order by disorder effect in magnetic field is studied for a classical Heisenberg antiferromagnet on the kagome lattice. Using analytical arguments we predict a unique H-T phase diagram for this strongly frustrated magnet: states with a coplanar and a uniaxial triatic order parameters respectively at low and high magnetic fields and an incompressible collinear spin-liquid state at a one-third of the saturation field. We also present the Monte Carlo data which confirm existence of these phases.Comment: 4 pages, 2 figures, accepted versio

Biliary Bicarbonate Secretion Constitutes a Protective Mechanism against Bile Acid-Induced Injury in Man

Background: Cholangiocytes expose a striking resistance against bile acids: while other cell types, such as hepatocytes, are susceptible to bile acid-induced toxicity and apoptosis already at micromolar concentrations, cholangiocytes are continuously exposed to millimolar concentrations as present in bile. We present a hypothesis suggesting that biliary secretion of HCO(3)(-) in man serves to protect cholangiocytes against bile acid-induced damage by fostering the deprotonation of apolar bile acids to more polar bile salts. Here, we tested if bile acid-induced toxicity is pH-dependent and if anion exchanger 2 (AE2) protects against bile acid-induced damage. Methods: A human cholangiocyte cell line was exposed to chenodeoxycholate (CDC), or its glycine conjugate, from 0.5 mM to 2.0 mM at pH 7.4, 7.1, 6.7 or 6.4, or after knockdown of AE2. Cell viability and apoptosis were determined by WST and caspase-3/-7 assays, respectively. Results: Glycochenodeoxycholate (GCDC) uptake in cholangiocytes is pH-dependent. Furthermore, CDC and GCDC (pK(a) 4-5) induce cholangiocyte toxicity in a pH-dependent manner: 0.5 mM CDC and 1 mM GCDC at pH 7.4 had no effect on cell viability, but at pH 6.4 decreased viability by >80% and increased caspase activity almost 10- and 30-fold, respectively. Acidification alone had no effect. AE2 knockdown led to 3- and 2-fold enhanced apoptosis induced by 0.75 mM CDC or 2 mM GCDC at pH 7.4. Discussion: These data support our hypothesis of a biliary HCO(3)(-) umbrella serving to protect human cholangiocytes against bile acid-induced injury. AE2 is a key contributor to this protective mechanism. The development and progression of cholangiopathies, such as primary biliary cirrhosis, may be a consequence of genetic and acquired functional defects of genes involved in maintaining the biliary HCO(3)(-) umbrella. Copyright (C) 2011 S. Karger AG, Base

Thermodynamic Study of Excitations in a 3D Spin Liquid

In order to characterize thermal excitations in a frustrated spin liquid, we have examined the magnetothermodynamics of a model geometrically frustrated magnet. Our data demonstrate a crossover in the nature of the spin excitations between the spin liquid phase and the high-temperature paramagnetic state. The temperature dependence of both the specific heat and magnetization in the spin liquid phase can be fit within a simple model which assumes that the spin excitations have a gapped quadratic dispersion relation.Comment: 5 figure

Transition to Long Range Magnetic Order in the Highly Frustrated Insulating Pyrochlore Antiferromagnet Gd_2Ti_2O_7

Experimental evidence from measurements of the a.c. and d.c. susceptibility, and heat capacity data show that the pyrochlore structure oxide, Gd_2Ti_2O_7, exhibits short range order that starts developing at 30K, as well as long range magnetic order at $T\sim 1$K. The Curie-Weiss temperature, $\theta_{CW}$ = -9.6K, is largely due to exchange interactions. Deviations from the Curie-Weiss law occur below $\sim$10K while magnetic heat capacity contributions are found at temperatures above 20K. A sharp maximum in the heat capacity at $T_c=0.97$K signals a transition to a long range ordered state, with the magnetic specific accounting for only $\sim$ 50% of the magnetic entropy. The heat capacity above the phase transition can be modeled by assuming that a distribution of random fields acts on the $^8S_{7/2}$ ground state for Gd$^{3+}$. There is no frequency dependence to the a.c. susceptibility in either the short range or long range ordered regimes, hence suggesting the absence of any spin-glassy behavior. Mean field theoretical calculations show that no long range ordered ground state exists for the conditions of nearest-neighbor antiferromagnetic exchange and long range dipolar couplings. At the mean-field level, long range order at various commensurate or incommensurate wave vectors is found only upon inclusion of exchange interactions beyond nearest-neighbor exchange and dipolar coupling. The properties of Gd$_2Ti_2O_7 are compared with other geometrically frustrated antiferromagnets such as the Gd_3Ga_5O_{12} gadolinium gallium garnet, RE_2Ti_2O_7 pyrochlores where RE = Tb, Ho and Tm, and Heisenberg-type pyrochlore such as Y_2Mo_2O_7, Tb_2Mo_2O_7, and spinels such as ZnFe_2O_4Comment: Letter, 6 POSTSCRIPT figures included. (NOTE: Figure 5 is not included --) To appear in Physical Review B. Contact: [email protected]

Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis

The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 × 10−32 and P = 1.8 × 10−22 in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (Hepatology 2011;53:1967-1976

Enhanced magnetocaloric effect in frustrated magnets

The magnetothermodynamics of strongly frustrated classical Heisenberg antiferromagnets on kagome, garnet, and pyrochlore lattices is examined. The field induced adiabatic temperature change (dT/dH)_S is significantly larger for such systems compared to ordinary non-frustrated magnets and also exceeds the cooling rate of an ideal paramagnet in a wide range of fields. An enhancement of the magnetocaloric effect is related to presence of a macroscopic number of soft modes in frustrated magnets below the saturation field. Theoretical predictions are confirmed with extensive Monte Carlo simulations.Comment: 7 page

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants