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1.  Behavioral Medicine Approaches to Chronic Obstructive Pulmonary Disease 
Background
Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease and associated with considerable individual and socioeconomic burden. Recent research started examining the role of psychosocial factors for course and management of the disease.
Purpose
This review provides an overview on recent findings on psychosocial factors and behavioral medicine approaches in COPD.
Results
Research has identified several important psychosocial factors and effective behavioral medicine interventions in COPD. However, there is considerable need for future research in this field.
Conclusions
Although beneficial effects of some behavioral medicine interventions have been demonstrated in COPD, future research efforts are necessary to study the effects of distinct components of these interventions, to thoroughly examine promising but yet not sufficiently proven interventions, and to develop new creative interventions.
doi:10.1007/s12160-012-9348-7
PMCID: PMC3612952  PMID: 22351032
Behavioral medicine; Chronic obstructive pulmonary disease; COPD; Psychosocial; Treatment
2.  The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing 
The EMBO Journal  2013;32(8):1115-1127.
Despite progress in mechanistic understanding of the RNA interference (RNAi) pathways, the subcellular sites of RNA silencing remain under debate. Here we show that loading of lipid-transfected siRNAs and endogenous microRNAs (miRNA) into RISC (RNA-induced silencing complexes), encounter of the target mRNA, and Ago2-mediated mRNA slicing in mammalian cells are nucleated at the rough endoplasmic reticulum (rER). Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT). Fractionation and membrane co-immune precipitations further confirm that siRNA-loaded Ago2 physically associates with the cytosolic side of the rER membrane. Additionally, RLC-associated double-stranded siRNA, diagnostic of RISC loading, and RISC-mediated mRNA cleavage products exclusively co-sediment with rER. Finally, we identify TRBP and PACT as key factors anchoring RISC to ER membranes in an RNA-independent manner. Together, our findings demonstrate that the outer rER membrane is a central nucleation site of siRNA-mediated RNA silencing.
The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing
This detailed characterization of membrane association in siRNA-mediated gene silencing establishes the rough ER as major site for canonical RISC loading and target RNA cleavage.
doi:10.1038/emboj.2013.52
PMCID: PMC3630355  PMID: 23511973
argonaute 2; microRNA; RNA interference; rough endoplasmatic reticulum; siRNA localization
3.  A Novel Multiplex Cell Viability Assay for High-Throughput RNAi Screening 
PLoS ONE  2011;6(12):e28338.
Cell-based high-throughput RNAi screening has become a powerful research tool in addressing a variety of biological questions. In RNAi screening, one of the most commonly applied assay system is measuring the fitness of cells that is usually quantified using fluorescence, luminescence and absorption-based readouts. These methods, typically implemented and scaled to large-scale screening format, however often only yield limited information on the cell fitness phenotype due to evaluation of a single and indirect physiological indicator. To address this problem, we have established a cell fitness multiplexing assay which combines a biochemical approach and two fluorescence-based assaying methods. We applied this assay in a large-scale RNAi screening experiment with siRNA pools targeting the human kinome in different modified HEK293 cell lines. Subsequent analysis of ranked fitness phenotypes assessed by the different assaying methods revealed average phenotype intersections of 50.7±2.3%–58.7±14.4% when two indicators were combined and 40–48% when a third indicator was taken into account. From these observations we conclude that combination of multiple fitness measures may decrease false-positive rates and increases confidence for hit selection. Our robust experimental and analytical method improves the classical approach in terms of time, data comprehensiveness and cost.
doi:10.1371/journal.pone.0028338
PMCID: PMC3230607  PMID: 22162763

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