Hippo effectors YAP/TAZ act as on–off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

BACKGROUND Extracellular vesicles (EVs) are cell‐derived membrane vesicles. EVs contain several RNAs such as mRNA, microRNAs, and ncRNAs, but less is known of their genomic DNA (gDNA) content. It is also unknown whether the DNA cargo is randomly sorted or if it is systematically packed into specific EV subpopulations. The aim of this study was to analyze whether different prostate cancer (PCa) cell‐derived EV subpopulations (apoptotic bodies, microvesicles, and exosomes) carry different gDNA fragments. METHODS EV subpopulations were isolated from three PCa cell lines (LNCaP, PC‐3, and RC92a/hTERT) and the plasma of PCa patients and healthy donors, and characterized by transmission electron microscopy, nanoparticle tracking analysis and total protein content. gDNA fragments of different genes were detected by real time quantitative PCR and confirmed by DNA sequencing. RESULTS We report that the concentration of EVs was higher in the cancer patients than in the healthy controls. EV subpopulations differed from each other in terms of total protein and DNA content. Analysis of gDNA fragments of MLH1, PTEN, and TP53 genes from the PCa cell‐derived EV subpopulations showed that different EVs carried different gDNA content, which could even harbor specific mutations. Altogether, these results suggest that both nucleic acids and proteins are selectively and cell‐dependently packed into the EV subtypes. CONCLUSIONS EVs derived from PCa cell lines and human plasma samples contain double‐stranded gDNA fragments which could be used to detect specific mutations, making EVs potential biomarkers for cancer diagnostics and prognostics. Prostate 74:1379–1390, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

Although new therapeutic approaches for burn treatment have made progress, there is still need for better methods to enhance wound healing and recovery especially in severely burned patients. Nanofibrillar cellulose (NFC) has gained attention due to its renewable nature, good biocompatibility and excellent physical properties that are of importance for a range of applications in pharmaceutical and biomedical fields. In the present study, we investigated the potential of a wood based NFC wound dressing in a clinical trial on burn patients. Previously, we have investigated NFC as a topical functionalized wound dressing that contributes to improve wound healing in mice. Wood based NFC wound dressing was tested in split-thickness skin graft donor site treatment for nine burn patients in clinical trials at Helsinki Burn Centre. NFC dressing was applied to split thickness skin graft donor sites. The dressing gradually dehydrated and attached to donor site during the first days. During the clinical trials, physical and mechanical properties of NFC wound dressing were optimized by changing its composition. From patient 5 forward, NFC dressing was compared to commercial lactocapromer dressing, Suprathel® (PMI Polymedics, Germany). Epithelialization of the NFC dressing-covered donor site was faster in comparison to Suprathel®. Healthy epithelialized skin was revealed under the detached NFC dressing. NFC dressing self-detached after 11-21days for patients 1-9, while Suprathel® self-detached after 16-28days for patients 5-9. In comparison studies with patients 5-9, NFC dressing self-detached on average 4days earlier compared with Suprathel®. Lower NFC content in the material was evaluated to influence the enhanced pliability of the dressing and attachment to the wound bed. No allergic reaction or inflammatory response to NFC was observed. NFC dressing did not cause more pain for patients than the traditional methods to treat the skin graft donor sites. Based on the preliminary clinical data, NFC dressing seems to be promising for skin graft donor site treatment since it is biocompatible, attaches easily to wound bed, and remains in place until donor site has renewed. It also detaches from the epithelialized skin by itself.

Several quality control (QC) procedures are available to detect errors in ground records of solar radiation, mainly range tests, model comparison and graphical analysis, but most of them are ineffective in detecting common problems that generate errors within the physical and statistical acceptance ranges. Herein, we present a novel QC method to detect small deviations from the real irradiance profile. The proposed method compares ground records with estimates from three independent radiation products, mainly satellite-based datasets, and flags periods of consecutive days where the daily deviation of the three products differs from the historical values for that time of the year and region. The confidence intervals of historical values are obtained using robust statistics and errors are subsequently detected with a window function that goes along the whole time series. The method is supplemented with a graphical analysis tool to ease the detection of false alarms. The proposed QC was validated in a dataset of 313 ground stations. Faulty records were detected in 31 stations, even though the dataset had passed the Baseline Surface Radiation Network (BSRN) range tests. The graphical analysis tool facilitated the identification of the most likely causes of these errors, which were classified into operational errors (snow over the sensor, soiling, shading, time shifts, large errors) and equipment errors (miscalibration and sensor replacements), and it also eased the detection of false alarms (16 stations). These results prove that our QC method can overcome the limitations of existing QC tests by detecting common errors that create small deviations in the records and by providing a graphical analysis tool that facilitates and accelerates the inspection of flagged values.JRC.C.2-Energy Efficiency and Renewable