Nuclear SR-protein mediated mRNA quality control is continued in cytoplasmic nonsense-mediated decay.

One important task of eukaryotic cells is to translate only mRNAs that were correctly processed to prevent the production of truncated proteins, found in neurodegenerative diseases and cancer. Nuclear quality control of splicing requires the SR-like proteins Gbp2 and Hrb1 in S. cerevisiae, where they promote the degradation of faulty pre-mRNAs. Here we show that Gbp2 and Hrb1 also function in nonsense mediated decay (NMD) of spliced premature termination codon (PTC)-containing mRNAs. Our data support a model in which they are in a complex with the Upf-proteins and help to transmit the Upf1-mediated PTC recognition to the transcripts ends. Most importantly they appear to promote translation repression of spliced transcripts that contain a PTC and to finally facilitate degradation of the RNA, presumably by supporting the recruitment of the degradation factors. Therefore, they seem to control mRNA quality beyond the nuclear border and may thus be global surveillance factors. Identification of SR-proteins as general cellular surveillance factors in yeast will help to understand the complex human system in which many diseases with defects in SR-proteins or NMD are known, but the proteins were not yet recognized as general RNA surveillance factors.

Dbp5/DDX19 between Translational Readthrough and Nonsense Mediated Decay.

The DEAD-box protein Dbp5 (human DDX19) remodels RNA-protein complexes. Dbp5 functions in ribonucleoprotein export and translation termination. Termination occurs, when the ribosome has reached a stop codon through the Dbp5 mediated delivery of the eukaryotic termination factor eRF1. eRF1 contacts eRF3 upon dissociation of Dbp5, resulting in polypeptide chain release and subsequent ribosomal subunit splitting. Mutations in DBP5 lead to stop codon readthrough, because the eRF1 and eRF3 interaction is not controlled and occurs prematurely. This identifies Dbp5/DDX19 as a possible potent drug target for nonsense suppression therapy. Neurodegenerative diseases and cancer are caused in many cases by the loss of a gene product, because its mRNA contained a premature termination codon (PTC) and is thus eliminated through the nonsense mediated decay (NMD) pathway, which is described in the second half of this review. We discuss translation termination and NMD in the light of Dbp5/DDX19 and subsequently speculate on reducing Dbp5/DDX19 activity to allow readthrough of the PTC and production of a full-length protein to detract the RNA from NMD as a possible treatment for diseases.

Development of a shear stress sensor to analyse the influence of polymers on the turbulent wall shear stress.

The drag reducing effect of polymers in a channel flow is well known and it is assumed that the polymer filaments interfere with the turbulent structures in the very near-wall flow. To analyse their precise effect, a micro-pillar shear stress sensor (MPS³) measurement system is developed which allows the detection of wall shear stress at high spatial and temporal resolutions. Different manufacturing techniques for the required micro-pillars are discussed and their influence on the flow is investigated evidencing the non-intrusive character of the pillars. Subsequently, a complete calibration is presented to relate the recorded deflection to wall shear stress values and to assure the correct detection over the whole expected frequency spectrum. A feasibility study about the ability to visualize the two-dimensional wall shear stress distribution completes the discussion about the validity of MPS³. In the last step, the drag reduction of a polymer filament grafted on a micro-pillar compared to a plain pillar and the application of MPS³ in an ocean-type polymer solution are investigated. The results confirm the expected behaviour found in the literature.

Micro-Particle Image Velocimetry (microPIV): recent developments, applications, and guidelines.

In this review we discuss the state of the art of the optical whole-field velocity measurement technique micro-scale Particle Image Velocimetry (microPIV). microPIV is a useful tool for fundamental research of microfluidics as well as for the detailed characterization and optimization of microfluidic applications in life science, lab-on-a-chip, biomedical research, micro chemical engineering, analytical chemistry and other related fields of research. An in depth description of the microPIV method is presented and compared to other flow visualization and measurement methods. An overview of the most relevant applications is given on the topics of near-wall flow, electrokinetic flow, biological flow, mixing, two-phase flow, turbulence transition and complex fluid dynamic problems. Current trends and applications are critically reviewed. Guidelines for the implementation and application are also discussed.

The Micro-Pillar Shear-Stress Sensor MPS(3) for Turbulent Flow.

Wall-shear stress results from the relative motion of a fluid over a body surface as a consequence of the no-slip condition of the fluid in the vicinity of the wall. To determine the two-dimensional wall-shear stress distribution is of utter importance in theoretical and applied turbulence research. In this article, characteristics of the Micro-Pillar Shear-Stress Sensor MPS(3), which has been shown to offer the potential to measure the two-directional dynamic wall-shear stress distribution in turbulent flows, will be summarized. After a brief general description of the sensor concept, material characteristics, possible sensor-structure related error sources, various sensitivity and distinct sensor performance aspects will be addressed. Especially, pressure-sensitivity related aspects will be discussed. This discussion will serve as 'design rules' for possible new fields of applications of the sensor technology.