Distinguishing Dismissing From Fearful Attachment in the Association Between Closeness and Commitment

When avoidantly attached individuals are simultaneously high in attachment anxiety, they are inclined to experience strong internal conflicts between seeking and avoiding closeness. This research examined whether the extent to which closeness, assessed as the inclusion of other in the self (IOS), is associated with greater commitment varies within individuals high in attachment avoidance as a result of differences in ambivalence toward maintaining the relationship. In two studies ( N1 = 1,604, N2 = 2,271), we found that the positive association between IOS and commitment was significantly weaker when attachment avoidance was combined with high (vs. low) attachment anxiety. In Study 2, we found lingering relational ambivalence even at high levels of IOS among individuals simultaneously high in attachment avoidance and anxiety, which in turn was related to relatively low commitment. Our findings highlight the role of relational ambivalence in avoidants’ relationship functioning and the need to examine the interplay of the two attachment dimensions. </jats:p

Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15

Abstract Background Enhanced metabolic plasticity and diversification of energy production is a hallmark of highly proliferative breast cancers. This contributes to poor pharmacotherapy efficacy, recurrence, and metastases. We have previously identified a mitochondrial-targeted furazano[3,4-b]pyrazine named BAM15 that selectively reduces bioenergetic coupling efficiency and is orally available. Here, we evaluated the antineoplastic properties of uncoupling oxidative phosphorylation from ATP production in breast cancer using BAM15. Methods The anticancer effects of BAM15 were evaluated in human triple-negative MDA-MB-231 and murine luminal B, ERα-negative EO771 cells as well as in an orthotopic allograft model of highly proliferative mammary cancer in mice fed a standard or high fat diet (HFD). Untargeted transcriptomic profiling of MDA-MB-231 cells was conducted after 16-h exposure to BAM15. Additionally, oxidative phosphorylation and electron transfer capacity was determined in permeabilized cells and excised tumor homogenates after treatment with BAM15. Results BAM15 increased proton leak and over time, diminished cell proliferation, migration, and ATP production in both MDA-MB-231 and EO771 cells. Additionally, BAM15 decreased mitochondrial membrane potential, while inducing apoptosis and reactive oxygen species accumulation in MDA-MB-231 and EO771 cells. Untargeted transcriptomic profiling of MDA-MB-231 cells further revealed inhibition of signatures associated with cell survival and energy production by BAM15. In lean mice, BAM15 lowered body weight independent of food intake and slowed tumor progression compared to vehicle-treated controls. In HFD mice, BAM15 reduced tumor growth relative to vehicle and calorie-restricted weight-matched controls mediated in part by impaired cell proliferation, mitochondrial respiratory function, and ATP production. LC-MS/MS profiling of plasma and tissues from BAM15-treated animals revealed distribution of BAM15 in adipose, liver, and tumor tissue with low abundance in skeletal muscle. Conclusions Collectively, these data indicate that mitochondrial uncoupling may be an effective strategy to limit proliferation of aggressive forms of breast cancer. More broadly, these findings highlight the metabolic vulnerabilities of highly proliferative breast cancers which may be leveraged in overcoming poor responsiveness to existing therapies

The chick chorioallantoic membrane imaging method as a platform to evaluate vasoactivity and assess irritancy of compounds

10.1111/j.2042-7158.2012.01506.xJournal of Pharmacy and Pharmacology6481128-1137JPPM