Effects of Synthetic Ligands on Heterodimer Pairs Regarding Full-Length Human PPARα, RXRα and LXRα

Nuclear receptor study is critically relevant in therapeutic medicine since the intricate details of disease states pertaining to atherosclerosis and diabetes are poorly understood. Three nuclear receptors of interest regulate target genes pertaining to cholesterol and fatty acid regulation, linking these receptors to therapeutic medicine. The first is the peroxisome proliferator-activated receptor alpha (PPARa), which resides in liver and muscle, coordinating lipoprotein and fatty acid homeostasis [1]. Cholesterol homeostasis is dictated by the liver X receptor alpha (LXRa), targeting genes pertaining to the kidney, intestine, liver and adipose tissues [2]. A common partner receptor to PPARa and LXRa is known as the retinoid X receptor alpha (RXRa) [3]. Although each receptor appears unique in function, the cause and effects of disease states are poorly understood due to the promiscuous nature of these receptor proteins. These particular receptors can form permissive heterodimers where metabolic effects can be manipulated by ligands [3]. Accordingly, clinical care becomes increasingly complex as synthetic ligands made to target one receptor could have additional repercussions. With respect to therapeutic medicine, ligand binding may not be exclusive. Therefore, it becomes necessary to study synthetic ligands with each receptor, individually and in heterodimeric form, to further understand the complex regulation and clinical implications of synthetic ligands on disease states such as atherosclerosis and diabetes

Molecular analysis of mammalian Neu4 sialidase gene promoter

Thesis (Master)--Izmir Institute of Technology, Biotechnology, Izmir, 2011Includes bibliographical referencesText in English; Abstract: Turkish and Englishix, 58 leavesThere are four different mammalian sialidases that have been described; lysosomal (Neu1), cytoplasmic (Neu2), plasma membrane (Neu3), lysosomal/mitochondrial (Neu4). The activity of sialidase Neu4 enzyme against sialic acid containing ganglioside GM2 has been demonstrated. Biological role of sialidase Neu4 enzyme has been shown by the transfection of neuroglia cells from a Tay-Sachs patient with a Neu4-expressing plasmid showed clearance of accumulated ganglioside GM2. It has been also shown that sialidase Neu4 enzyme is responsible for degradation reactions of another ganglioside such as GD1a in brains of Neu4-/- mice. Aim of our study is to identify minimal promoter region of human Neu4 gene and demonstrate binding of transcription factors to this region. In our study, we used bioinformatic approaches to predict the sequence motifs where several specific transcription factors bind using TESS (Transcription Element Seach System) tool. We amplified seven different DNA fragments from human Neu4 promoter region, cloned into luciferase expression vector and performed reporter assay. We also performed electrophoretic mobility shift assay to demonstrate binding of transcription factors to candidate promoter region. We demonstrated that 187 bp upstream of Neu4 gene is minimal promoter region to control transcription from Neu4 gene. Electrophoretic mobility shift assay showed that 187 bp upstream region recruits several transcription factors. Our results demonstrated the minimal promoter region revealing several putative transcription factors such as Sp-1 and c-myc which might be responsible mainly for regulation of Neu4 gene transcription. The data we obtained might be useful to discover small molecules which can control Neu4 gene expression. High expression of Neu4 gene might be controlled using drugs or small molecules and the accumulated GM2 ganglioside in lysosomes of Tay-Sachs patients can be reduced

Young Adults Getting Involved: Participatory Action Research & Transition Age Youth

Research presented on improving supports for transition age youth and young adults who have serious mental health conditions and want to complete schooling and training to move into work lives, through actively participating in the research and dissemination process

Delman Jack - Callison College One Pager

https://scholarlycommons.pacific.edu/callison-college-sis/1032/thumbnail.jp

Disparities in Vocational Supports for Black Young Adults with Mental Health Conditions

This research brief discusses the disparities in vocational rehabilitation (VR) services and supports that Black young adults with mental health conditions face when compared to their White peers. It touches on what the disparities this population faces in VR are, research on barriers and facilitators to employment for Black young adults, engagement and access to vocational services and areas for future study

Young Adults Getting Involved: Participatory Action Research and Transition Age Youth [English, Vietnamese, and Spanish versions]

Vietnamese and Spanish translations of this publication are available for download under Additional Files below. Describes the positive outcomes when young adults take part in participatory action research. Originally published as: Research You Can Use, Issue 4, 2011. Also issued as Transitions RTC Tip Sheet 1, Feb. 2011

Peer led Recovery Learning Communities: Expanding Social Integration Opportunities for People with the Lived Experience of Psychiatric Disability and Emotional Distress

Social integration is the development of mutually supportive relationships with other community members. For people with psychiatric disabilities (PD) social integration is a critical aspect of mental wellness and recovery. While people with PD generally want supportive friends, their social networks tend to be weak, often limited to treatment staff and close family. The barriers to social integration of people with PD are often high, and include public discrimination, lack of confidence, and insufficient financial resources. In the United States, community mental health providers have focused primarily on illness management and have not successfully helped clients integrate socially.  To fill that gap, people with lived experience of psychiatric disability have for many years established networks of peer support, including peer-facilitated groups. With the aim of enhancing that approach, peers in Massachusetts developed the “Recovery Learning Community” model, a regional network of peer support and education operated and staffed by people with lived experience, are distinct from most other peer run programs in that they provide meetings and workshops in various community locations, not only in a single location. In this article, we describe conceptually and with examples the significant impact RLCs have on both the social integration of people with PD and the delivery of mental health services in United States and internationally

The History of Mining in Cerro de Pasco and Heavy Metal Deposition in Lake Junin Peru

Lake Junín covers 530-km2 and is located at 4,430-m in an intermontane basin between the eastern and western cordillera of the central Peruvian Andes. The lake sits between the large sulfide mining districts of La Oroya and Cerro de Pasco. Designated a National Reserve in 1974, Lake Junín drains northward to the Río San Juan, which joins the Río Mantaro within several kilometers of the lake. Dam construction by the Cerro de Pasco Copper Corporation on the Río Mantaro in 1932 caused the Río San Juan, the principal river draining Cerro de Pasco, to back up into the lake. Using an ICP-MS, this report documents the contamination of Lake Junín with Co, Cu, Zn, Pb, Fe, and Mn; constrains the timing of the heavy metal pollution by correlating the δ18O record of a Lake Junín Core with a core from nearby Lake Pumacocha; and quantifies the contribution of heavy metals delivered via surficial runoff by comparing metal concentrations in Lake Junín sediments with those of Lake Pumacocha, which receives heavy metals only through atmospheric deposition and airfall. We analyzed six sediment cores, and the results reveal dramatic peaks in most metal concentrations at depths ranging from 10-55 cm below the sediment surface. Comparison of the sediment record from Lake Junín with Lake Pumacocha indicates that metal laden sediment transported into Lake Junín from the Río San Juan has formed a deposit with concentrations at least one order of magnitude greater than lakes that received only atmospherically transported metals

Relationships as the Foundation of Shared Decision Making: The Experience of Young Adults with Mental Health Conditions

To describe the experience of young adults with serious mental illness as active participants in making medication decisions with their psychiatrists