Inflammasome and IL-1β-Mediated Disorders

The NLRP3 inflammasome is an intracellular complex that regulates the release of proinflammatory cytokines such as interleukin-1β in response to exogenous pathogens and endogenous danger signals. Evidence from studies involving human genetics, human ex vivo mononuclear cell responses, and in vivo and in vitro murine models confirms the importance of the inflammasome and interleukin-1β in the pathogenesis of several inherited and complex diseases. The availability of several effective interleukin-1β targeted therapies has allowed for successful proof-of-concept studies in several of these disorders. However, many other diseases are likely to be mediated by the inflammasome and interleukin-1β, providing additional targets in the future

Cold-induced urticaria with a familial transmission: a case report and review of the literature

Abstract Introduction Cryopyrin-associated periodic syndrome is a rare genetic disorder causing cold-induced urticaria, severe arthralgias, and (potentially) renal failure and hearing loss. Therapies that effectively control the symptoms and prevent the complications of this debilitating disorder are now available, making recognition of this disease important. Case presentation A 60-year-old Caucasian woman presented with complaints of rash and joint pains to a general medicine clinic. Her history showed that her symptoms were linked to cold exposure, but the results of a cold stimulation time test were negative. Several generations of her family had similar symptoms. Conclusions This case highlights the importance of considering cryopyrin-associated periodic syndrome in the differential diagnosis of cold-induced urticaria. Several medications targeting interleukin-1-beta are available, providing significant relief from symptoms and improvement in quality of life in affected patients.</p

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Lepton Acceleration in Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) act as calorimeters for the relativistic pair winds emanating from within the pulsar light cylinder. Their radiative dissipation in various wavebands is significantly different from that of their pulsar central engines: the broadband spectra of PWNe possess characteristics distinct from those of pulsars, thereby demanding a site of lepton acceleration remote from the pulsar magnetosphere. A principal candidate for this locale is the pulsar wind termination shock, a putatively highly-oblique, ultra-relativistic MHD discontinuity. This paper summarizes key characteristics of relativistic shock acceleration germane to PWNe, using predominantly Monte Carlo simulation techniques that compare well with semi-analytic solutions of the diffusion-convection equation. The array of potential spectral indices for the pair distribution function is explored, defining how these depend critically on the parameters of the turbulent plasma in the shock environs. Injection efficiencies into the acceleration process are also addressed. Informative constraints on the frequency of particle scattering and the level of field turbulence are identified using the multiwavelength observations of selected PWNe. These suggest that the termination shock can be comfortably invoked as a principal injector of energetic leptons into PWNe without resorting to unrealistic properties for the shock layer turbulence or MHD structure.Comment: 19 pages, 5 figures, invited review to appear in Proc. of the inaugural ICREA Workshop on "The High-Energy Emission from Pulsars and their Systems" (2010), eds. N. Rea and D. Torres, (Springer Astrophysics and Space Science series

Two Energy Scales and two Quasiparticle Dynamics in the Superconducting State of Underdoped Cuprates

The superconducting state of underdoped cuprates is often described in terms of a single energy-scale, associated with the maximum of the (d-wave) gap. Here, we report on electronic Raman scattering results, which show that the gap function in the underdoped regime is characterized by two energy scales, depending on doping in opposite manners. Their ratios to the maximum critical temperature are found to be universal in cuprates. Our experimental results also reveal two different quasiparticle dynamics in the underdoped superconducting state, associated with two regions of momentum space: nodal regions near the zeros of the superconducting gap and antinodal regions. While antinodal quasiparticles quickly loose coherence as doping is reduced, coherent nodal quasiparticles persist down to low doping levels. A theoretical analysis using a new sum-rule allows us to relate the low-frequency-dependence of the Raman response to the temperature-dependence of the superfluid density, both controlled by nodal excitations.Comment: 16 pages, 5 figure

Aneurysm of an autologous aorta to right coronary artery reverse saphenous vein graft presenting as a mediastinal mass: a case report

Aneurysmal dilation of saphenous vein grafts is a relatively rare complication of the now common surgical procedure of coronary artery bypass graft (CABG) surgery. The true prevalence of this condition is not clear, however, literature review by Jorgensen et. al. between 1975 and 2002 revealed only 76 published cases. [1] Recent review of literature, utilizing OVID (search terms: saphenous vein, aneurysm, graft, pseudoaneurysm, coronary bypass) suggests a significantly higher prevalence with 14 such cases published in a variety of multinational journals during the period of 2006 to April 2007. The causes of this dramatic increase is likely multifactorial, however, in the author's opinion, likely reflects the increased sophistication and utilization of cross sectional imaging modalities. Regardless of the true prevalence of the condition, there is little debate that the potential for serious morbidity and mortality in this patient population is significant, and that increased detection and discussion of viable therapeutic options is critical. [1] Therefore, we present a case report and discussion of a patient with symptomatic cardiac ischemia, found to have a large saphenous vein graft aneurysm (SVGA) on coronary CTA

Telepresence and the Role of the Senses

The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al