224 research outputs found
The voice of song : a prosodic and phonological approach to William Blake
Thesis (M.A.) -- University of Adelaide, Dept. of English, 198
Eviction Prevention Programming (EPP): Best Practices Review Feb 2015
There is no question that eviction is bad news for renters. Forced moves put individuals and families at risk in so many ways: They have a more difficult time being accepted as tenants elsewhere; they frequently are disconnected from social-support networks, health care providers, employment and schools; and the stress takes a psychological toll of its own.For property owners and managers, turnover means additional expense for legal procedures, recruitment of new tenants and apartment make-ready. But in the nonprofit, mission-oriented world, it's not just about money; it's also about addressing the underlying challenges that drive nonpayment of rent to begin with. The question is what (resident) services are most successful as well as cost efficient. This is the issue this study set out to explore
The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1 pulmonary circulation
Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with
dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent
development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of
PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that
an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH.
Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was
attenuated by the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative
stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression
was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged
survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by
an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased
SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This
promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate
that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy
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