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Transcription co-activators CBP and p300 are recruited by sequence-specific transcription factors to specific genomic loci to control gene expression. A highly conserved domain in CBP/p300, the TAZ2 domain, mediates direct interaction with a variety of transcription factors including the myocyte enhancer factor 2 (MEF2). Here we report the crystal structure(More)
Methods for detecting circulating microRNAs (miRNAs), small RNAs that control gene expression, at high sensitivity and specificity in the blood have been reported in recent studies. The goal of this study was to determine if detectable levels of specific miRNAs are released into the circulation for bevacizumab-induced cardiotoxicity. A miRNA array analysis(More)
Although interleukin (IL)-1 beta activates the hypothalamic-pituitary-adrenal (HPA) axis, the mechanisms by which peripheral IL-1 beta acutely stimulates adrenocorticotropin (ACTH) secretion are not clear. Recently, the vagus has been implicated in mediating peripheral cytokine signalling of the brain. To investigate a possible central mechanism for(More)
In this study the expression of pl6INK4, retinoblastoma protein (pRb), and cdk4 proteins have been examined in 18 malignant glioma cell lines and in 45 malignant glial tumors. Loss of pl6INK4 expression associated with pl61NKi gene homozygous deletion was evident in 12 cell lines and in 10 primary tumors. Lack of pl6INK4 expression was also evident in five(More)
Temporal changes in tyrosine hydroxylase (TH) mRNA levels in medullary A1 and A2 neurons and locus coeruleus (LC) cells were studied 6, 12 and 24 h following orchidectomy in rats. Brains from intact controls and sham castrated rats also were evaluated at these same time periods. In situ hybridization histochemistry and quantitative image analysis techniques(More)
We have applied restriction fragment length polymorphism analysis to a 30-member panel of primary glioma DNAs, which had been previ ously examined for loss of genetic information (C. to determine the frequency and sublocalization of loss of genetic information from chromosome 9. We have also utilized scanning densitometry for dosage determination of the(More)
The FYVE domain associates with phosphatidylinositol 3-phosphate [PtdIns(3)P] in membranes of early endosomes and penetrates bilayers. Here, we detail principles of membrane anchoring and show that the FYVE domain insertion into PtdIns(3)P-enriched membranes and membrane-mimetics is substantially increased in acidic conditions. The EEA1 FYVE domain binds to(More)
The pleckstrin homology (PH) domain of the general receptor for phosphoinositides 1 (GRP1) exhibits specific, high-affinity, reversible binding to phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)) at the plasma membrane, but the nature and extent of the interaction between this bound complex and the surrounding membrane environment remains unclear.(More)
Morphine not only suppresses norepinephrine-induced increases in LHRH mRNA levels but, in these same animals, it simultaneously amplifies norepinephrine (NE)-induced LH release. These observations suggest that NE may activate parallel mechanisms which independently increase LHRH mRNA levels and LHRH release and suggest that some of these effects could be(More)
These studies determined whether endogenous gamma-aminobutyric acid (GABA) secretion affects LHRH neuronal responsiveness to norepinephrine (NE). The intracerebroventricular (icv) infusion of either bicuculline or phaclofen (GABA-A or GABA-B receptor antagonists, respectively) into ovariectomized (OVX) estrogen-treated rats did not affect basal LH levels(More)