19 research outputs found
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Effect of halogen substitution on the enthalpies of solvation and hydrogen bonding of organic solutes in chlorobenzene and 1,2-dichlorobenzene derived using multi-parameter correlations
Article on the effect of halogen substitution on the enthalpies of solvation and hydrogen bonding of organic solutes in chlorobenzene and 1,2-dichlorobenzene derived using multi-parameter correlations
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Enthalpies of solution and enthalpies of solvation of organic solutes in ethylene glycol at 298.15 K: prediction and analysis of intermolecular interaction contributions
This article studies thermochemistry of solvation of inert gases and organic solutes in ethylene glycol was thoroughly studied using solution calorimetry technique
c-IAP1 and c-IAP2 Are Critical Mediators of Tumor Necrosis Factor α (TNFα)-induced NF-κB Activation*S⃞
The inhibitor of apoptosis (IAP) proteins are a family of anti-apoptotic
regulators found in viruses and metazoans. c-IAP1 and c-IAP2 are recruited to
tumor necrosis factor receptor 1 (TNFR1)-associated complexes where they can
regulate receptor-mediated signaling. Both c-IAP1 and c-IAP2 have been
implicated in TNFα-stimulated NF-κB activation. However,
individual c-IAP1 and c-IAP2 gene knock-outs in mice did not
reveal changes in TNF signaling pathways, and the phenotype of a combined
deficiency of c-IAPs has yet to be reported. Here we investigate the role of
c-IAP1 and c-IAP2 in TNFα-stimulated activation of NF-κB. We
demonstrate that TNFα-induced NF-κB activation is severely
diminished in the absence of both c-IAP proteins. In addition, combined
absence of c-IAP1 and c-IAP2 rendered cells sensitive to TNFα-induced
cell death. Using cells with genetic ablation of c-IAP1 or cells where the
c-IAP proteins were eliminated using IAP antagonists, we show that
TNFα-induced RIP1 ubiquitination is abrogated in the absence of c-IAPs.
Furthermore, we reconstitute the ubiquitination process with purified
components in vitro and demonstrate that c-IAP1, in collaboration
with the ubiquitin conjugating enzyme (E2) enzyme UbcH5a, mediates
polymerization of Lys-63-linked chains on RIP1. Therefore, c-IAP1 and c-IAP2
are required for TNFα-stimulated RIP1 ubiquitination and NF-κB
activation
APRIL-Deficient Mice Have Normal Immune System Development
APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL(−/−) mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions
Caspase-8 Serves Both Apoptotic and Nonapoptotic Roles
Knockout of caspase-8, a cysteine protease that participates in the signaling for cell death by receptors of the TNF/nerve growth factor family, is lethal to mice in utero. To explore tissue-specific roles of this enzyme, we established its conditional knockout using the Cre/loxP recombination system. Consistent with its role in cell death induction, deletion of caspase-8 in hepatocytes protected them from Fas-induced caspase activation and death. However, application of the conditional knockout approach to investigate the cause of death of caspase-8 knockout embryos revealed that this enzyme also serves cellular functions that are nonapoptotic. Its deletion in endothelial cells resulted in degeneration of the yolk sac vasculature and embryonal death due to circulatory failure. Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death. Thus, besides participating in cell death induction by receptors of the TNF/nerve growth factor family, caspase-8, apparently independently of these receptors, also mediates nonapoptotic and perhaps even antiapoptotic activities