The strategy for evaluating template-based models submitted to CASP has continuously evolved from CASP1 to CASP5, leading to a standard procedure that has been used in all subsequent editions. The established approach includes methods for calculating the quality of each individual model, for assigning scores based on the distribution of the results for each target and for computing the statisti...

Introduction The proinflammatory enzyme caspase-1 belongs to the family of cystein proteases and plays a pivotal role in innate immunity. Classically, caspase-1 mediated proinflammatory signaling is thought to be dependent on its enzymatic activity. Interestingly, a number of patients carrying variants of the CASP1 gene show proinflammatory symptoms like febrile episodes despite of reduced enzy...

Circular RNAs (circRNAs) are a novel class of non-coding RNA which have recently shown huge capabilities in the regulation of gene expression at the post-transcriptional level. Growing evidence has indicated that circRNAs could serve as competing endogenous RNAs (ceRNAs) to bind with microRNAs (miRNAs) and to inhibit the activity and function of the targeted miRNAs. Here, we demonstrated that c...

Listeriolysin O (LLO), an hly-encoded cytolysin from Listeria monocytogenes, plays an essential role in the entry of this pathogen into the macrophage cytoplasm and is also a key factor in inducing the production of IFN-gamma during the innate immune stage of infection. In this study, we examined the involvement of LLO in macrophage production of the IFN-gamma-inducing cytokines IL-12 and IL-18...

Caspase-1 promotes both the maturation of proinflammatory cytokines and apoptosis in cells infected by certain pathogens. Work by now reveals a surprising new function for caspase-1: the stimulation of membrane biogenesis to repair damage caused by bacterial pore-forming toxins. Thus, caspase-1 may promote host cell survival as a means of resistance to pathogenic bacteria.

Novel therapeutic targets against which we can develop medications are urgently needed in the field of Alzheimer Disease (AD) research. While immense progress has been made in the description and diagnosis of AD, no effective medication to prevent or treat AD exists. Yet, 47 million individuals suffer from AD worldwide. The cost to care for AD and other dementias is $259 billion dollars/year in...

The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macr...

Bladder dysfunction is common in Multiple Sclerosis (MS) but little is known of its pathophysiology. We show that mice with experimental autoimmune encephalomyelitis (EAE), a MS model, have micturition dysfunction and altered expression of genes associated with bladder mechanosensory, transduction and signaling systems including pannexin 1 (Panx1) and Gja1 (encoding connexin43, referred to here...

Background The systemic subtype of juvenile idiopathic arthritis (sJIA) can be the most severe, and unlike other forms of JIA is an autoinflammatory disease. There is evidence for the involvement of IL-1 in sJIA: treatment with the IL-1 receptor agonist, Anakinra, has shown dramatic improvement in some sJIA patients. Additionally we have shown a significant association with members of the IL-1 ...

Inflammasome activation permits processing of interleukins (IL)-1β and 18 and elicits cell death (pyroptosis). Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1) activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, th...