Gene expression profiling of the long-term adaptive response to hypoxia in the gills of adult zebrafish

Animal science

New Results for the Correlation Functions of the Ising Model and the Transverse Ising Chain

In this paper we show how an infinite system of coupled Toda-type nonlinear differential equations derived by one of us can be used efficiently to calculate the time-dependent pair-correlations in the Ising chain in a transverse field. The results are seen to match extremely well long large-time asymptotic expansions newly derived here. For our initial conditions we use new long asymptotic expansions for the equal-time pair correlation functions of the transverse Ising chain, extending an old result of T.T. Wu for the 2d Ising model. Using this one can also study the equal-time wavevector-dependent correlation function of the quantum chain, a.k.a. the q-dependent diagonal susceptibility in the 2d Ising model, in great detail with very little computational effort.Comment: LaTeX 2e, 31 pages, 8 figures (16 eps files). vs2: Two references added and minor changes of style. vs3: Corrections made and reference adde

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Geological, geochemical, and geophysical survey of the geothermal resources at Hot Springs Bay Valley, Akutan Island, Alaska

An extensive survey was conducted of the geothermal resource potential of Hot Springs Bay Valley on Akutan Island. A topographic base map was constructed, geologic mapping, geophysical and geochemical surveys were conducted, and the thermal waters and fumarolic gases were analyzed for major and minor element species and stable isotope composition. (ACR

Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia.

We prospectively studied 45 anaemic patients (37 women, 8 men) with chronic inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as well as ESR) in its predictive capacity for bone marrow iron stores was examined. The relationship between other iron-related measurements (transferrin, transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores was also investigated. Stainable bone marrow iron was taken as the most suitable standard to separate iron-deficient from iron-replete patients. 14 patients (31%) were lacking bone marrow iron. Regression analysis showed a good correlation between ferritin and bone marrow iron (adjusted R2 = 0.721, P < 0.0001). The combination of ferritin and CRP (ESR) did not improve the predictive power for bone marrow iron (adjusted R2 = 0.715) in this cohort of patients with low systemic inflammatory activity. With respect to the bone marrow iron content the best predictive cut-off value of ferritin was 30 micrograms/l (86% sensitivity, 90% specificity). The other iron-related parameters both individually and when combined were less powerful in predicting bone marrow iron than ferritin alone. Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly improved prediction (adjusted R2 = 0.731). A cut-off point of 11% hypochromic erythrocytes reached a high specificity (90%), but was less sensitive (77%)

ANTI-CD74 ANTIBODIES AS DIAGNOSTIC BIOMARKER FOR EARLY AXIAL SPONDYLOARTHRITIS: DATA FROM THE SPONDYLOARTHRITIS CAUGHT EARLY (SPACE) COHORT STUDY

Pathophysiology and treatment of rheumatic disease