31421212
New regulators of NF-κB in inflammation
Research on the biological function of nuclear factor-κB (NF-κB), a key mediator of inducible transcription in the immune system, has traditionally focused on its role in the initiation of innate and adaptive immune responses. These studies have largely concentrated on the mechanisms of signalling that lead to NF-κB activation and on the positive role of NF-κB in both physiological immunity and pathological inflammation. More recently, there has been growing interest in the mechanisms that directly regulate the NF-κB transcriptional programmes. As a result, several new NF-κB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-κB.
15459299
Missing Pieces in the NF-κB Puzzle
The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.
37212550
Management of Crohn’s disease from efficacy, quality of life and health economic perspectives
The expectations of the physician and patient in the modern management of Crohn’s disease have moved on from alleviation of symptoms whenever relapses occur, to sustained maintenance of remission and mucosal healing. The majority of treatment costs are as a consequence of hospitalizations and surgery. These heightened therapeutic goals are leading to expectations that management costs will decrease. Health-related quality of life can be measured by validated disease-specific tools in Crohn’s disease, and such measurements are now forming common outcome measures in clinical trials of new therapies in Crohn’s disease. This review gives an overview of patient-focused management of Crohn’s disease and the rapid evolution in therapy, with pharmacoeconomic analysis where available.
12424757
Endotoxin-induced organ injury.
OBJECTIVE
To review the effects of endotoxemia on the major organ systems of the body and discuss potential mechanisms of tissue injury.


DESIGN
Appraisal of 60 articles representing a cross section of studies relating to in vivo and in vitro responses to endotoxin.


MAIN METHODS
Cell cultures, isolated tissue preparations, animal and human studies.


RESULTS
Endotoxemia results in the activation of numerous cellular and hematogenous mediators. These mediators range from prostaglandins, thromboxanes, and leukotrienes, to complement components. Tumor necrosis factor may be responsible for initiating many of the observed responses to endotoxin. Species and tissue specificity are a prominent feature of the response to endotoxin.


CONCLUSIONS
No single agent can yet be implicated as the common mediator of endotoxin-induced organ injury. Endotoxin initiates the elaboration of a cascade of secondary mediators that amplify the response to the initial insult. The relative importance of individual agents as mediators of the response to endotoxin varies with the experimental model studied.
6526989
Isolation and characterization of superdormant spores of Bacillus species.
Superdormant spores of Bacillus subtilis and Bacillus megaterium were isolated in 4 to 12% yields following germination with high nutrient levels that activated one or two germinant receptors. These superdormant spores did not germinate with the initial nutrients or those that stimulated other germinant receptors, and the superdormant spores' defect was not genetic. The superdormant spores did, however, germinate with Ca(2+)-dipicolinic acid or dodecylamine. Although these superdormant spores did not germinate with high levels of nutrients that activated one or two nutrient germinant receptors, they germinated with nutrient mixtures that activated more receptors, and using high levels of nutrient mixtures activating more germinant receptors decreased superdormant spore yields. The use of moderate nutrient levels to isolate superdormant spores increased their yields; the resultant spores germinated poorly with the initial moderate nutrient concentrations, but they germinated well with high nutrient concentrations. These findings suggest that the levels of superdormant spores in populations depend on the germination conditions used, with fewer superdormant spores isolated when better germination conditions are used. These findings further suggest that superdormant spores require an increased signal for triggering spore germination compared to most spores in populations. One factor determining whether a spore is superdormant is its level of germinant receptors, since spore populations with higher levels of germinant receptors yielded lower levels of superdormant spores. A second important factor may be heat activation of spore populations, since yields of superdormant spores from non-heat-activated spore populations were higher than those from optimally activated spores.
21780213
Interfacial and self-aggregation of binary mixtures of anionic and nonionic amphiphiles in aqueous medium.
Interfacial and bulk properties of sodium dodecyl sulfate (SDS), polyoxyethylene (20) sorbitan monooleate (Tween-80), and their binary mixtures in aqueous medium have been investigated using surface tension, conductance, and fluorescence measurements at different temperatures. The critical micelle concentration (CMC), counterion binding, polarity index, aggregation number, thermodynamics of interfacial adsorption, and micellization are evaluated. The entropic contribution is found to be the predominant factor in micelle formation. The aggregation number and the polarity index of the micelle interior estimated by the pyrene fluorescence technique show interesting temperature dependence. The size and composition of the mixed micelles vary with the total concentration. The micellar compositions, activities of the individual components in the mixed species, and intersurfactant interactions are also estimated following regular solution theory, excess thermodynamic functions, and a molecular thermodynamic model. The surfactant mixtures are found to be nonideal with a lower degree of counterion binding compared to the individual members. Mixed micelles are nonspherical in nature at all temperatures when the mole fraction (α) of the ionic part in mixtures is high but transform to spherical when α(SDS) is ≤0.50.
21393419
Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival.
The TSC1-TSC2 complex has recently been implicated in cell survival responses. We observed that NF-kappaB signaling is attenuated in TSC1- and TSC2-deficient MEFs concomitant with reduced survival following DNA damage or TNFalpha stimulation. Reconstitution of TSC2 expression in TSC2(-/-) MEFs rescued survival in an NF-kappaB activity-dependent manner. Furthermore, in TSC2(-/-) MEFs, the rapamycin-mediated inhibition of deregulated mTOR activity restored NF-kappaB activation and survival. This rapamycin-mediated effect was reversed by inhibition of NF-kappaB transcriptional activation or by inhibition of ERK1/2 MAP kinase or PI-3K pathways, which lie on signaling cascades that lead to NF-kappaB activation. These results provide evidence for a crosstalk between the TSC/Rheb/mTOR pathway and the NF-kappaB induction pathways and indicate that NF-kappaB functions as an important survival factor that regulates TSC2-dependent cell survival.