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Investigated attachment security and behavior in 34 physically disabled infants and 26 non-disabled infants using convergent, categorical, and continuous (Attachment Behavior Q-Set) measures of relationship, based on the same set of home observations. Proportions of attachment classifications were identical for each group, but insecure disabled infants scored consistently lower on the AQS security score than insecure non-disabled infants. (TJQ)

Nuclear receptors can activate diverse biological pathways within a target cell in response to their cognate ligands, but how this compartmentalization is achieved at the level of gene regulation is poorly understood. We used a genome-wide analysis of promoter occupancy by the estrogen receptor [alpha] (ER[alpha]) in MCF-7 cells to investigate the molecular mechanisms underlying the action of 17[beta]-estradiol ([E.sub.2]) in controlling the growth of breast cancer cells. We identified 153 promoters bound by ER[alpha] in the presence of [E.sub.2]. Motif-finding algorithms demonstrated that the estrogen response element (ERE) is the most common motif present in these promoters whereas conventional chromatin immunoprecipitation assays showed [E.sub.2]-modulated recruitment of coactivator AIB1 and RNA polymerase II at these loci. The promoters were linked to known ER[alpha] targets but also to many genes not directly associated with the estrogenic response, including the transcriptional factor FOXA1, whose expression correlates with the presence of ER[alpha] in breast tumors. We found that ablation of FOXA1 expression in MCF-7 cells suppressed ER[alpha] binding to the prototypic TFF1 promoter (which contains a FOXA1 binding site), hindered the induction of TFF1 expression by [E.sub.2], and prevented hormone-induced reentry into the cell cycle. Taken together, these results define a paradigm for estrogen action in breast cancer cells and suggest that regulation of gene expression by nuclear receptors can be compartmentalized into unique transcriptional domains by means of licensing of their activity to cofactors such as FOXA1. ChIP-on-chip | forkhead box | transcription | cell cycle

The article describes that IFN [gamma] induces the expression of many nuclear genes encoding mitochondrial respiratory chain machinery through activation of the nuclear receptor ERR [alpha]. This shows that ERR[gamma] and PGC [beta] together act as a key effector of IFN- [gamma] induced mitochondrial ROS production and host defence.

Loss of dopaminergic neurons is primarily responsible for the onset and progression of Parkinson's disease (PD); thus, neuroprotective and/or neuroregenerative strategies remain critical to the treatment of this increasingly prevalent disease. Here we explore a novel approach to neurotrophic factor-based therapy by engineering zinc finger protein transcription factors (ZFP IFs) that activate the expression of the endogenous glial cell line-derived neurotrophic factor (GDNF) gene. We show that GDNF activation can be achieved with exquisite genome-wide specificity. Furthermore, in a rat model of PD, striatal delivery of an adeno-associated viral vector serotype 2 encoding the GDNF activator resulted in improvements in forelimb akinesia, sensorimotor neglect, and amphetamine-induced rotations caused by 6-hydroxydopamine (6-OHDA) lesion. Our results suggest that an engineered ZFP IF can drive sufficient GDNF expression in the brain to provide functional neuroprotection against 6-OHDA; therefore, targeted activation of the endogenous gene may provide a method for delivering appropriate levels of GDNF to PD patients. [ABSTRACT FROM AUTHOR]