Cell-selective glucocorticoid receptor (GR) binding to distal regulatory elements is associated with cell type-specific regions of locally accessible chromatin. These regions can either pre-exist in chromatin (pre-programmed) or be induced by the receptor (de novo). Mechanisms that create and maintain these sites are not well understood. We observe a global enrichment of CpG density for pre-programmed elements, and implicate their demethylated state in the maintenance of open chromatin in a tissue-specific manner. In contrast, sites that are actively opened by GR (de novo) are characterized by low CpG density, and form a unique class of enhancers devoid of suppressive effect of agglomerated methyl-cytosines. Furthermore, treatment with glucocorticoids induces rapid changes in methylation levels at selected CpGs within de novo sites. Finally, we identify GR-binding elements with CpGs at critical positions, and show that methylation can affect GR-DNA interactions in vitro. The findings present a unique link between tissue-specific chromatin accessibility, DNA methylation and transcription factor binding and show that DNA methylation can be an integral component of gene regulation by nuclear receptors.

Domestic violence is not as simple as one partner physically harming another. Instead, it consists of a complex range of controlling behaviors including physical, emotional, sexual, and economic maltreatment as well as isolation, male privilege, blaming, intimidation, threats, and minimizing/denying behaviors. In addition to the controlling behaviors reported by women seeking shelter from violent relationships, a growing body of research indicates some individuals who abuse their intimate partner also abuse their pets. This study explores these connections using reports of 1,283 female pet owners seeking refuge from their male batterer in a domestic violence shelter. Findings indicate that batterers who also abuse their pet (a) use more forms of violence and (b) demonstrate greater use of controlling behaviors than batterers who do not abuse their pets. Likewise, positive correlations are found between specific controlling behaviors and cruelty to pets. Implications for practice and future research are discussed.

Numerous biochemical and structural studies have shown that the conformation of the estrogen receptor alpha (ERalpha) can be influenced by ligand binding. In turn, the conformational state of ERalpha affects the ability of the receptor to interact with a wide variety of protein accessory factors. To globally investigate ligand-based cofactor recruitment activities of ERalpha, we have applied a flow cytometric multiplexed binding assay to determine the simultaneous binding of ERalpha to over 50 different peptides derived from both known cofactor proteins and random peptide phage display. Using over 400 ERalpha-binding compounds, we have observed that the multiplexed in vitro peptide-binding profiles are distinct for a number of compounds and that these profiles can predict the effect that ERalpha ligands have on various cellular activities. These cell-based activities include transcriptional regulation at an estrogen response element, MCF-7 cell proliferation, and Ishikawa endometrial cell stimulation. The majority of the compound-induced diversity in the peptide profiling assay is provided by the unique phage display peptides. Importantly, some of these peptides show a sequence relationship with the corepressor motif, suggesting that peptides identified via phage display might represent natural binding partners of ERalpha. These in vitro:cellular correlations may in part explain tissue-specific activities of ERalpha-modulating compounds.

The current study addresses the validation of the Checklist of Controlling Behaviors (CCB), an 84-item domestic violence assessment instrument that can be used to address multiple levels of violence and coercive control in violent relationships. Derived from clinical observation and current theories, the CCB makes use of intimate partner violence survivor reports to identify the intensity and frequency of relationship violence. The instrument is divided into 10 subscales including (1) physical abuse, (2) sexual abuse, (3) male privilege, (4) isolation, (5) minimizing and denying, (6) blaming, (7) intimidation, (8) threats, (9) emotional abuse, and (10) economic abuse. To assess validity and reliability of the CCB, 2,135 female volunteers taking refuge at a domestic violence shelter were administered the instrument. Results of principal component analysis of the individual subscales revealed 10 factors having goodness-of-fit values above the desired normative level of .90.

Exploring the relationship between parenting and women's use of violence the current study surveyed 106 mothers arrested for intimate partner violence (IPV) related crimes on parenting styles and attitudes toward when using violence against their partner is justified. Findings indicate parenting styles indicative of low belief in using physical discipline with their child/ children and an internal parental locus of control. However, a moderate to weak relationship between parenting styles and justification for using violence against a partner was also found. Although some support for the spillover theory is noted, results are far from conclusive.

Objective Evaluate changes in end-of-life care following initiation of a Palliative Care Program in a neonatal intensive care unit. Study Design Retrospective study comparing infant deaths before and after implementation of a Palliative Care Program comprised of medication guidelines, an individualized order set, a nursing care plan, and staff education. Result 82 infants died before (Era 1) and 68 infants died after implementation of the program (Era 2). Morphine use was similar [88% vs. 81%; p=0.17], while benzodiazepines use increased in Era 2 [26% vs. 43%; p=0.03]. Withdrawal of life support (73% vs. 63%; p=0.17) and do-not-resuscitate orders (46% vs. 53%; p=0.42) were similar. Do-not-resuscitate orders and family meetings were more frequent among Era 2 infants with activated palliative care orders (n=21) compared to infants without activated orders (n=47). Conclusion End-of-life family meetings and benzodiazepine use increased following implementation of our program, likely reflecting adherence to guidelines and improved communication.

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Traditional approaches to discovery of selective estrogen receptor modulators (SERMs) have relied on ER binding and cell-based estrogen response element-driven assays to identify compounds that are osteoprotective but nonproliferative in breast and uterine tissues. To discover new classes of potential SERMs, we have employed a cell-free microsphere-based binding assay to rapidly characterize ERalpha interactions with conformation-sensing cofactor or phage display peptides. Peptide profiles of constrained triarenes were compared to known proliferative and nonproliferative ER ligands to discover potent quinoline-based ligands with minimal Ishikawa cell stimulation.