Alternative signaling pathways from IGF1 or insulin to AKT activation and FOXO1 nuclear efflux in adult skeletal muscle fibers.

Muscle atrophy is regulated by the balance between protein degradation and synthesis. FOXO1, a transcription factor, helps to determine this balance by activating pro-atrophic gene transcription when present in muscle fiber nuclei. Foxo1 nuclear efflux is promoted by AKT-mediated Foxo1 phosphorylation, eliminating FOXO1's atrophy-promoting effect.

Consumer experiences of home care packages.

Objective: The study aimed to explore consumers' experiences of receiving a home care package (HCP).

Methods: Community engagement was used to recruit older people approved for a HCP. Data were collected through face-to-face interviews, and data analysis identified themes.

Foxo1 nucleo-cytoplasmic distribution and unidirectional nuclear influx are the same in nuclei in a single skeletal muscle fiber but vary between fibers.

Foxo transcription factors promote protein breakdown and atrophy of skeletal muscle fibers. Foxo transcriptional effectiveness is largely determined by phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-green fluorescent protein (GFP) over time in 124 nuclei in 68 multinucleated adult skeletal muscle fibers under control culture conditions reveals large variability between fibers in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in the apparent rate coefficient ( kI') for Foxo1-GFP unidirectional nuclear influx (measured with efflux blocked by leptomycin B).

Identification of a multienzyme complex for glucose metabolism in living cells.

Sequential metabolic enzymes in glucose metabolism have long been hypothesized to form multienzyme complexes that regulate glucose flux in living cells. However, it has been challenging to directly observe these complexes and their functional roles in living systems. In this work, we have used wide-field and confocal fluorescence microscopy to investigate the spatial organization of metabolic enzymes participating in glucose metabolism in human cells.

Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers.

Prevention and slowing of skeletal muscle atrophy with nutritional approaches offers the potential to provide far-reaching improvements in the quality of life for our increasingly aging population. Here we show that polyphenol flavonoid epigallocatechin 3-gallate (EGCG), found in the popular beverage green tea (Camellia sinensis), demonstrates similar effects to the endogenous hormones insulin-like growth factor 1 (IGF-1) and insulin in the ability to suppress action of the atrophy-promoting transcription factor Foxo1 through a net translocation of Foxo1 out of the nucleus as monitored by nucleo-cytoplasmic movement of Foxo1-green fluorescent protein (GFP) in live skeletal muscle fibers. Foxo1-GFP nuclear efflux is rapid in IGF-1 or insulin, but delayed by an additional 30 min for EGCG.

Dynamic architecture of the purinosome involved in human de novo purine biosynthesis.

Enzymes in human de novo purine biosynthesis have been demonstrated to form a reversible, transient multienzyme complex, the purinosome, upon purine starvation. However, characterization of purinosomes has been limited to HeLa cells and has heavily relied on qualitative examination of their subcellular localization and reversibility under wide-field fluorescence microscopy. Quantitative approaches, which are particularly compatible with human disease-relevant cell lines, are necessary to explicitly understand the purinosome in live cells.

Logic models as a tool for sexual violence prevention program development.

Sexual violence is a growing public health problem, and there is an urgent need to develop sexual violence prevention programs. Logic models have emerged as a vital tool in program development. The Centers for Disease Control and Prevention funded an empowerment evaluation designed to work with programs focused on the prevention of first-time male perpetration of sexual violence, and it included as one of its goals, the development of program logic models.

Staying well with bipolar disorder.

Objective: The research aimed to investigate how people diagnosed with bipolar mood disorder avoided episodes of illness and managed to stay well. The research also examined the role that personal, social and environmental factors played in helping people with bipolar mood disorder to stay well.

Method: This project used a combination of qualitative research methods.

The primary substrate binding site in the b' domain of ERp57 is adapted for endoplasmic reticulum lectin association.

ERp57 is a member of the protein disulfide isomerase (PDI) family that is located in the endoplasmic reticulum (ER) and characterized by its specificity for glycoproteins. Substrate selection by ERp57 is dependent upon its formation of discrete complexes with two ER resident lectins, soluble calreticulin and membrane-bound calnexin. It is these two lectins that directly associate with glycoproteins bearing correctly trimmed oligosaccharide side chains.