49 research outputs found
Non-extremal black holes of N=2, d=4 supergravity
We propose a generic recipe for deforming extremal black holes into
non-extremal black holes and we use it to find and study the non-extremal
black-hole solutions of several N=2,d=4 supergravity models (SL(2,R)/U(1), CPn
and STU with four charges). In all the cases considered, the non-extremal
family of solutions smoothly interpolates between all the different extremal
limits, supersymmetric and not supersymmetric. This fact can be used to find
explicitly extremal non-supersymmetric solutions in the cases in which the
attractor mechanism does not completely fix the values of the scalars on the
event horizon and they still depend on the boundary conditions at spatial
infinity.
We compare (supersymmetry) Bogomol'nyi bounds with extremality bounds, we
find the first-order flow equations for the non-extremal solutions and the
corresponding superpotential, which gives in the different extremal limits
different superpotentials for extremal black holes. We also compute the
"entropies" (areas) of the inner (Cauchy) and outer (event) horizons, finding
in all cases that their product gives the square of the moduli-independent
entropy of the extremal solution with the same electric and magnetic charges.Comment: Many small, inessential changes. Some misprints corrected and a few
references adde
A Human TREK-1/HEK Cell Line: A Highly Efficient Screening Tool for Drug Development in Neurological Diseases
TREK-1 potassium channels are involved in a number of physiopathological processes such as neuroprotection, pain and depression. Molecules able to open or to block these channels can be clinically important. Having a cell model for screening such molecules is of particular interest. Here, we describe the development of the first available cell line that constituvely expresses the TREK-1 channel. The TREK-1 channel expressed by the h-TREK-1/HEK cell line has conserved all its modulation properties. It is opened by stretch, pH, polyunsaturated fatty acids and by the neuroprotective molecule, riluzole and it is blocked by spadin or fluoxetine. We also demonstrate that the h-TREK-1/HEK cell line is protected against ischemia by using the oxygen-glucose deprivation model
UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review
BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications
Two Coregulated Efflux Transporters Modulate Intracellular Heme and Protoporphyrin IX Availability in Streptococcus agalactiae
Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia. This pathogen does not synthesize heme, but scavenges it from blood to activate a respiration metabolism, which increases bacterial cell density and is required for full virulence. Factors that regulate heme pools in S. agalactiae are unknown. Here we report that one main strategy of heme and protoporphyrin IX (PPIX) homeostasis in S. agalactiae is based on a regulated system of efflux using two newly characterized operons, gbs1753 gbs1752 (called pefA pefB), and gbs1402 gbs1401 gbs1400 (called pefR pefC pefD), where pef stands for âporphyrin-regulated effluxâ. In vitro and in vivo data show that PefR, a MarR-superfamily protein, is a repressor of both operons. Heme or PPIX both alleviate PefR-mediated repression. We show that bacteria inactivated for both Pef efflux systems display accrued sensitivity to these porphyrins, and give evidence that they accumulate intracellularly. The ÎpefR mutant, in which both pef operons are up-regulated, is defective for heme-dependent respiration, and attenuated for virulence. We conclude that this new efflux regulon controls intracellular heme and PPIX availability in S. agalactiae, and is needed for its capacity to undergo respiration metabolism, and to infect the host
Outer membrane protein folding from an energy landscape perspective
The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the ÎČ-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding