34 research outputs found
Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis
Inflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.Bronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.Hematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function
Understanding Novel Superconductors with Ab Initio Calculations
This chapter gives an overview of the progress in the field of computational
superconductivity.
Following the MgB2 discovery (2001), there has been an impressive
acceleration in the development of methods based on Density Functional Theory
to compute the critical temperature and other physical properties of actual
superconductors from first-principles. State-of-the-art ab-initio methods have
reached predictive accuracy for conventional (phonon-mediated) superconductors,
and substantial progress is being made also for unconventional superconductors.
The aim of this chapter is to give an overview of the existing computational
methods for superconductivity, and present selected examples of material
discoveries that exemplify the main advancements.Comment: 38 pages, 10 figures, Contribution to Springer Handbook of Materials
Modellin
Subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain: a longitudinal study
Hypomanic Symptoms in Female Undergraduate Students Diagnosed with Unipolar Depression Based on Scores on the Hypomania Checklist
Doping dependence of spin excitations and its correlations with high-temperature superconductivity in iron pnictides
In conventional Bardeen-Cooper-Schrieffer (BCS) superconductors,
superconductivity occurs when electrons form coherent Cooper pairs below the
superconducting transition temperature Tc. Although the kinetic energy of
paired electrons increases in the superconducting state relative to the normal
state, the reduction in the ion lattice energy is sufficient to give the
superconducting condensation energy. For iron pnictide superconductors derived
from electron or hole doping of their antiferromagnetic (AF) parent compounds,
the microscopic origin for supercnductivity is unclear. Here we use neutron
scattering to show that high-Tc superconductivity only occurs for iron
pnictides with low-energy itinerant electron-spin excitation coupling and high
energy spin excitations. Since our absolute spin susceptibility measurements
for optimally hole-doped iron pnictide reveal that the change in magnetic
exchange energy below and above Tc can account for the superconducting
condensation energy, we conclude that the presence of both high-energy spin
excitations giving rise to a large magnetic exchange coupling J and low-energy
spin excitations coupled to the itinerant electrons is essential for high-Tc
superconductivity in iron pnictides.Comment: 9 pages, 4 figures in the main article; 11 pages, 13 figures in the
supplementary material
Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi
Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens