Regulation and glucocorticoid-independent induction of lipocortin I in cultured astrocytes.

Stimulation of prostaglandin (PG) release in rat astroglial cultures by various substances, including phorbol esters, melittin, or extracellular ATP, has been reported recently. It is shown here that glucocorticoids (GCs) reduced both basal and stimulated PGD2 release. Hydrocortisone, however, did not inhibit ATP-, calcium ionophore A23187-, or tetradecanoyl phorbol acetate (TPA)-stimulated arachidonic acid release, and only TPA stimulations were affected by dexamethasone. GC-mediated inhibition of PGD2 release thus appeared to exclude regulation at the phospholipase A2 (PLA2) level. Therefore, the effects of GCs on the synthesis of lipocortin I (LC I), a potent, physiological inhibitor of PLA2, were studied in more detail. Dexamethasone was not able to enhance de novo synthesis of LC I in freshly seeded cultures and failed to increase LC I synthesis in 2-3-week-old cultures. It is surprising that LC I was the major LC synthesized in those cultures, and marked amounts accumulated with culture time, reaching plateau levels at approximately day 10. In contrast, LC I was barely detectable in vivo. This tonic inhibition of PLA2 is the most likely explanation for unsuccessful attempts to evoke PG release in astrocyte cultures by various physiological stimuli. GC receptor antagonists (progesterone and RU 38486) given throughout culture time reduced LC I accumulation and simultaneously increased PGD2 release. Nonetheless, a substantial production of LC I persisted in the presence of antagonists. Therefore, LC I induction did not seem to involve GC receptor activation. This was confirmed in serum- and GC-free brain cell aggregate cultures. Here also a marked accumulation of LC I was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Vortices and extreme black holes: The question of flux expulsion

It has been claimed that extreme black holes exhibit a phenomenon of flux expulsion for Abelian Higgs vortices, irrespective of the relative width of the vortex to the black hole. Recent work by two of the authors showed a subtlety in the treatment of the event horizon, which cast doubt on this claim. We analyze in detail the vortexextreme black hole system, showing that, while flux expulsion can occur, it does not do so in all cases. We give analytic proofs for both expulsion and penetration of flux, in each case deriving a bound for that behavior. We also present extensive numerical work backing up, and refining, these claims, and showing in detail how a vortex can end on a black hole in all situations. We also calculate the back reaction of the vortex on the geometry, and comment on the more general vortexblack hole system.

Cosmic rays as probes of large extra dimensions and TeV gravity

If there are large extra dimensions and the fundamental Planck scale is at the TeV scale, then the question arises of whether ultrahigh energy cosmic rays might probe them. We study the neutrino-nucleon cross section in these models. The elastic forward scattering is analyzed in some detail, hoping to clarify earlier discussions. We also estimate the black hole production rate. We study energy loss from graviton mediated interactions and conclude that they cannot explain the cosmic ray events above the GZK energy limit. However, these interactions could start horizontal air showers with characteristic profile and at a rate higher than in the standard model.

NLRC5, at the Heart of Antigen Presentation.

Nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are intracellular proteins mainly involved in pathogen recognition, inflammatory responses, and cell death. Until recently, the function of the family member NLR caspase recruitment domain (CARD) containing 5 (NLRC5) has been a matter of debate. It is now clear that NLRC5 acts as a transcriptional regulator of the major-histocompatibility complex class I. In this review we detail the development of our understanding of NLRC5 function, discussing both the accepted and the controversial aspects of NLRC5 activity. We give insight into the molecular mechanisms, and the potential implications, of NLRC5 function in health and disease.