Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris

YesEpithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator−activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator−activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator−activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris

Acoustic far-field hypersonic surface wave detection with single plasmonic nanoantennas

The optical properties of small metallic particles allow us to bridge the gap between the myriad of subdiffraction local phenomena and macroscopic optical elements. The optomechanical coupling between mechanical vibrations of Au nanoparticles and their optical response due to collective electronic oscillations leads to the emission and the detection of surface acoustic waves (SAWs) by single metallic nanoantennas. We take two Au nanoparticles, one acting as a source and the other as a receptor of SAWs and, even though these antennas are separated by distances orders of magnitude larger than the characteristic subnanometric displacements of vibrations, we probe the frequency content, wave speed, and amplitude decay of SAWs originating from the damping of coherent mechanical modes of the source. Two-color pump-probe experiments and numerical methods reveal the characteristic Rayleigh wave behavior of emitted SAWs, and show that the SAW-induced optical modulation of the receptor antenna allows us to accurately probe the frequency of the source, even when the eigenmodes of source and receptor are detuned

The large Thaumasia graben on Mars: Is it a rift?

We investigate the morphology and topography of one of the largest fault-bounded tectonic structures on Mars, a complex, approximately N-S trending system of troughs and scarps at the western border of the Thaumasia plateau in the Claritas region (hereinafter referred to as “Thaumasia graben,” or TG). It is located between 15°S and 38°S latitude and at ∼255°E longitude. No detailed investigation of its morphotectonic setting has been performed yet. The region is a complexly fractured area with a number of different fault sets, including simple and complex graben. The TG extends over more than 1000 km along its trend, averaging 100 km in width and 1.6 km in depth. Crustal extension is accommodated by the formation of a system of asymmetric graben, or halfgraben. On the basis of fault orientation and trough depth, the TG can be subdivided in a north-south direction into three segments. Except for the northernmost segment, the predominant master fault system is located along the eastern flank of the TG, highlighting the overall asymmetric architecture. Fault length segments vary from 50 to 90 km with observable displacements of 1.3–2.2 km. Crustal extension, inferred from gridded MOLA topography across scarp offsets, varies along trend between 0.5 km and ∼4 km, assuming a fault dip of 60°. This is relatively moderate extension if compared to terrestrial continental rifts, but consistent with extension measured across the Tempe Rift on Mars. We find that the Thaumasia graben displays some characteristics which are common to terrestrial continental rifts, whereas other properties are distinctively not rift-like

Production of Embryonic and Fetal-Like Red Blood Cells from Human Induced Pluripotent Stem Cells

We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications

INPUT DEVICE RESEARCH FOR DIGITAL PATHOLOGY. AN ERGONOMIC OUTLOOK

Introduction/ Background Digital Pathology represents a technological innovation that introduces changes in the traditional work of pathologists. In this regard, an important issue that has not been enough emphasized is the image handling from an ergonomic point of view to avoid work-related musculoskeletal disorders (MSD). Aims The aim of this study was to investigate a proper input device for digital pathology. Methods Research was conducted in two phases: 1. Comparative study to find an optimal external controller. Eight medical students analyzed 11 input devices: keyboard (HP), conventional mouse (HP), vertical mouse (CLS), touchpad (Logitech), 3 trackballs (Logitech, Kensington Expert and Ulove), Rollermouse (Contour), Ergopointer (Märzhäuser Sensotech), gamepad (Logitech) and a touchless device (Leap-Motion), using them with the Image Viewer software (Ventana). The web-based Fitts´ law test (UC Berkeley) was used to objectify the accuracy of each device, randomly. 12 items were included in the questionnaire: comfort, technical aspects (cursor movement and objective achievement), prospects, overall satisfaction, prior experience, and others. 2. Evaluation by two experienced pathologists (MPR and ANO, 55 and 50 year-old, respectively) the best rated input device and comparison with a voice recognition system (Invox Medical Dictation) using a headset microphone (Plantronics), rating perceived workload using NASA Task Load Index with 28 whole slide images. Digital Image Hub (Leica) with a 4 MegaPixel display (Barco) was used. Data were processed with SPSS 21.0. Results Correlation between technical aspects of the evaluated devices and accuracy (Fitts´ law test), and comfort with overall satisfaction existed (p<0.05). The assessment concluded that vertical mouse was the best rated input device. However, it has a slightly higher perceived workload in comparison with the voice recognition system, which was the proper controller for digital pathology in this study. Conclusion: We describe a methodology that can study and compare input devices for future workstations in digital pathology. Pathologists should be involved in this process trying to find ergonomic devices that prevent MSD. Voice recognition can function as a good handsfree device for digital pathology and could be considered in physical disability situations. Further studies using electromyography, accelerometry and 3D reconstruction analysis could provide additional ergonomic information

Empirically-grounded development of legal ontologies: a socio-legal perspective

This paper shows the multiple relationships between empirical data and semantic content in the legal field. One of the well-known problems of ontology construction is the "knowledge acquisition bottleneck problem" pointed out by Edward Feigenbaum and others, many years ago. In the next generation of Semantic Web developments this problem has not been completely solved. It is our con-tention that an accurate description of the legal environment, and well-grounded previous sociological studies may help to face it in a more satisfactory way. This means adopting a user-centered approach for legal ontologies, in what we will call an "iterative and integrated pragmatic circle" involving legal theorists, socio-legal researchers, professional people (lawyers, magistrates, prosecutors…) and com-puter scientists. We put the example of how the ontology of IURISERVICE was built up