A protocol for retrospective translational science case studies of health interventions.

The critical processes driving successful research translation remain understudied. We describe a mixed-method case study protocol for analyzing translational research that has led to the successful development and implementation of innovative health interventions. An overarching goal of these case studies is to describe systematically the chain of events between basic, fundamental scientific discoveries and the adoption of evidence-based health applications, including description of varied, long-term impacts.

The IN/OUT assay: a new tool to study ciliogenesis.

Background: Nearly all cells have a primary cilia on their surface, which functions as a cellular antennae. Primary cilia assembly begins intracellularly and eventually emerges extracellularly. However, current ciliogenesis assays, which detect cilia length and number, do not monitor ciliary stages.

Zn2+ efflux through lysosomal exocytosis prevents Zn2+-induced toxicity.

Zn(2+) is an essential micronutrient and an important ionic signal whose excess, as well as scarcity, is detrimental to cells. Free cytoplasmic Zn(2+) is controlled by a network of Zn(2+) transporters and chelating proteins. Recently, lysosomes became the focus of studies in Zn(2+) transport, as they were shown to play a role in Zn(2+)-induced toxicity by serving as Zn(2+) sinks that absorb Zn(2+) from the cytoplasm.

Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease.

Zinc-dependent lysosomal enlargement in TRPML1-deficient cells involves MTF-1 transcription factor and ZnT4 (Slc30a4) transporter.

Zinc is critical for a multitude of cellular processes, including gene expression, secretion and enzymatic activities. Cellular zinc is controlled by zinc-chelating proteins and by zinc transporters. The recent identification of zinc permeability of the lysosomal ion channel TRPML1 (transient receptor potential mucolipin 1), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for TRPML1 in zinc transport.