E2 attenuates hemodynamic and remodeling parameters in HPH in an ER-dependent manner, through direct antiproliferative mechanisms on vascular cells, which may provide novel nonhormonal therapeutic targets for HPH.

Coccidioidomycosis consists of a spectrum of disease, ranging from a mild, self-limited, febrile illness to severe, life-threatening infection. It is caused by the soil-dwelling fungi, Coccidioides immitis and C. posadasii, which are present in diverse endemic areas. Climate changes and environmental factors affect the Coccidioides lifecycle and influence infection rates. The incidence of coccidioidomycosis has risen substantially over the past two decades. The vast majority of Coccidioides infections occur in the endemic zones, such as California, Arizona, Mexico, and Central America. Infections occurring outside those zones appear to be increasingly common, and pose unique clinical and public health challenges. It has long been known that elderly persons, pregnant women, and members of certain ethnic groups are at risk for severe or disseminated coccidioidomycosis. In recent years, it has become evident that persons with immunodeficiency diseases, diabetics, transplant recipients, and prisoners are also particularly vulnerable.

Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states.

The Hedgehog (Hh) pathway was first defined by its role in segment polarity in the Drosophila melanogaster embryonic epidermis and has since been linked to many aspects of vertebrate development and disease. In humans, mutation of the Patched1 (PTCH1) gene, which encodes an inhibitor of Hh signaling, lead to tumors of the skin and pediatric brain. Despite the high level of conservation between the vertebrate and invertebrate Hh pathways, studies in Drosophila have yet to find direct evidence that ptc limits organ size. Here we report identification of Drosophila ptc in a screen for mutations that require a synergistic apoptotic block in order to drive overgrowth. Developing imaginal discs containing clones of ptc mutant cells immortalized by the concurrent loss of the Apaf-1-related killer (Ark) gene are overgrown due, in large part, to the overgrowth of wild type portions of these discs. This phenotype correlates with overexpression of the morphogen Dpp in ptc,Ark double-mutant cells, leading to elevated phosphorylation of the Dpp pathway effector Mad (p-Mad) in cells surrounding ptc,Ark mutant clones. p-Mad functions with the Hippo pathway oncoprotein Yorkie (Yki) to induce expression of the pro-growth/anti-apoptotic microRNA bantam. Accordingly, Yki activity is elevated among wild type cells surrounding ptc,Ark clones and alleles of bantam and yki dominantly suppress the enlarged-disc phenotype produced by loss of ptc. These data suggest that ptc can regulate Yki in a non-cell autonomous manner and reveal an intercellular link between the Hh and Hippo pathways that may contribute to growth-regulatory properties of the Hh pathway in development and disease.

This study assessed the Anti-Stigma Project workshop, a contact/education intervention developed by On Our Own of Maryland, Inc. and the Maryland Mental Hygiene Administration. Two separate randomized controlled trials administered pre- and post-test questionnaire assessments. One included people with mental illness (N = 127) and a second included mental health providers (N = 131). Post-intervention, people with mental illness were more aware of stigma, had lower levels of prejudice, and increased belief in recovery. Providers were more aware of stigma, had lower levels of prejudice, and increased concurrence in self-determination of people with mental illness. Increasing providers' stigma awareness and recognition can promote higher quality service delivery. Increasing stigma awareness and recognition for people with mental illness can foster confidence in overcoming psychiatric disabilities. Using a participatory action research team, our protocol included extant and newly developed stigma change tools. Organizations seeking to conduct effective evaluation studies should consider collaborative processes including the expertise of affected constituents.