Autoinflammatory Disease Reloaded: A Clinical Perspective

Our understanding of the etiology of autoinflammatory disease is growing rapidly. Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed

Effective Sample Size: Quick Estimation of the Effect of Related Samples in Genetic Case-Control Association Analyses

Correlated samples have been frequently avoided in case-control
genetic association
 studies in part because the methods for handling them are either not
easily implemented or not widely known. We
advocate one method for case-control association analysis of correlated
samples -- the effective sample size method -- as a simple and
accessible approach that does not require specialized computer programs.
The effective sample size method captures the variance inflation
of allele frequency estimation exactly, and can be used to modify the
chi-square test statistic, p-value, and 95% confidence interval of
odds-ratio simply by replacing the apparent number of allele counts with the
effective ones. For genotype frequency estimation, although a single
effective sample size is unable to completely characterize the variance inflation,
an averaged one can satisfactorily approximate the simulated result.
The effective sample size method is applied to the rheumatoid arthritis
siblings data collected from the North American Rheumatoid Arthritis Consortium (NARAC)
to establish a significant association with the interferon-induced
helicasel gene (IFIH1) previously being identified as a type 1 diabetes
susceptibility locus. Connections between the effective sample size
method and other methods, such as generalized estimation equation,
variance of eigenvalues for correlation matrices, and genomic controls,
are also discussed.
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Insect reproductive behaviors are important mediators of carrion nutrient release into soil

Current declines in terrestrial insect biomass and abundance have raised global concern for the fate of insects and the ecosystem services they provide. However, the ecological and economic contributions of many insects have yet to be quantified. Carrion-specializing invertebrates are important mediators of carrion decomposition; however, the role of their reproductive activities in facilitating this nutrient pulse into ecosystems is poorly understood. Here, we investigate whether insects that sequester carrion belowground for reproduction alter soil biotic and abiotic properties in North American temperate forests. We conducted a field experiment that measured soil conditions in control, surface carrion alone, and beetle-utilized carrion treatments. Our data demonstrate that Nicrophorus beetle reproduction and development results in changes in soil characteristics which are consistent with those observed in surface carrion decomposition alone. Carrion addition treatments increase soil labile C, DON and DOC, while soil pH and microbial C:N ratios decrease. This study demonstrates that the decomposition of carrion drives soil changes but suggests that the behaviors of insect scavengers play an important role in the release of carrion nutrients directly into the soil by sequestering carrion resources in the ecosystem where they were deposited

Use of Oxyrase® enzyme to enhance recovery of Escherichia coli O157:H7 from culture media and ground beef

Escherichia coli O157:H7 is a bacterium that has caused great concern in the meat and food industry during the last few years because of several, well-publicized, disease outbreaks, including the incident at the Jackin- the-Box fast food chain in Seattle, Washington. The organism can cause severe sickness and even death in certain population groups. To better assure meat safety, federal meat inspection is focusing on developing rapid methods to detect this disease agent and others. Oxyrase is a commercially available enzyme that can accelerate the growth of some bacteria. Current techniques for isolation and culturing of E. coli O157:H7 from foods require an enrichment period of 18 to 24 hours, thus limiting their usefulness for perishable foods that are marketed quickly. Our investigation found that Oxyrase shortened required enrichment periods in broth culture only. The enzyme was less effective in sterilized ground beef

Microbial flora of commercially produced vacuum packaged, cooked beef roast

Commercially produced vacuum packaged, fully cooked, microwaveable beef roasts from four producers were purchased from local retail markets. Salt concentration, pH, water activity (aw), and percent moisture, fat and protein were determined. Samples of both package juice and homogenized beef plus juice were analyzed for the presence of aerobic, anaerobic and lactic acid bacteria and clostridia-type organisms. The cooked beef products had pH values from 5.82 to 6.19, water activity of 0.992 to 0.997, and contained 0.34 to 1.07% salt, 61.89 to 72.39% moisture, 4.29 to 18.21% fat and 15.92 to 20.62% protein. No growth was detected in juice for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Combined beef and juice had less than 2 CFU/g for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Cooking and chilling schedules used in the manufacture of the four products we evaluated in this study limited survival and outgrowth of microorganisms

MF2293

Fadi Aramouni et al, Food safety, Kansas State University, October 1997

Pyrin Modulates the Intracellular Distribution of PSTPIP1

PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease-associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are thought to share a common pathoetiology. The studies outlined here describe several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associated filaments in native and transfected cells. An extended FCH (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self-aggregation. We further show that the PSTPIP1 filament network is dependent upon an intact tubulin cytoskeleton and that the distribution of this network can be modulated by pyrin, indicating that this is a dynamic structure. Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein. ASC specks are associated with inflammasome activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin to ASC specks with particularly high efficiency, suggesting a unique mechanism underlying the robust inflammatory phenotype of PAPA syndrome

Critical Signaling Events in the Mechanoactivation of Human Mast Cells through p.C492Y-ADGRE2

A role for the adhesion G-protein coupled receptor ADGRE2 or EMR2 in mechanosensing was revealed by the finding of a missense substitution (p.C492Y) associated with familial vibratory urticaria. In these patients, friction of the skin induces mast cell hyper-degranulation through p.C492Y-ADGRE2, causing localized hives, flushing, and hypotension. We have now characterized the responses and intracellular signals elicited by mechanical activation in human mast cells expressing p.C492Y-ADGRE2 and attached to dermatan sulfate, a ligand for ADGRE2. The presence of p.C492Y-ADGRE2 reduced the threshold to activation and increased the extent of degranulation along with the percentage of mast cells responding. Vibration caused phospholipase C activation, transient increases in cytosolic calcium, and downstream activation of phosphoinositide 3-kinase and extracellular signaleregulated kinases 1 and 2 by Gbg, Gaq/11, and Gai/o-independent mechanisms. Degranulation induced by vibration was dependent on phospholipase C pathways, including calcium, protein kinase C, and phosphoinositide 3-kinase but not extracellular signaleregulated kinases 1/2 pathways, along with pertussis toxin-sensitive signals. In addition, mechanoactivation of mast cells stimulated the synthesis and release of prostaglandin D2, to our knowledge a previously unreported mediator in vibratory urticaria, and extracellular signaleregulated kinases 1/2 activation was required for this response together with calcium, protein kinase C, and to some extent, phosphoinositide 3-kinase. Our studies thus identified critical molecular events initiated by mechanical forces and potential therapeutic targets for patients with vibratory urticaria.This work was supported by the Division of Intramural Research within the National Institute of Allergy and Infectious Diseases and the National Human Genome Research Institute at the National Institutes of Health.S

From second to first order transitions in a disordered quantum magnet

We study the spin-glass transition in a disordered quantum model. There is a region in the phase diagram where quantum effects are small and the phase transition is second order, as in the classical case. In another region, quantum fluctuations drive the transition first order. Across the first order line the susceptibility is discontinuous and shows hysteresis. Our findings reproduce qualitatively observations on LiHo$_x$Y$_{1-x}$F$_4$. We also discuss a marginally stable spin-glass state and derive some results previously obtained from the real-time dynamics of the model coupled to a bath.Comment: 4 pages, 3 figures, RevTe