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

Inhibition of Hotspot Formation in Polymer Bonded Explosives Using an Interface Matching Low Density Polymer Coating at the Polymer–Explosive Interface

In order to elucidate how shocks in heterogeneous materials affect decomposition and reactive processes, we used the ReaxFF reactive force field in reactive molecules dynamics (RMD) simulations of the effects of strong shocks (2.5 and 3.5 km/s) on a prototype polymer bonded explosive (PBX) consisting of cyclotrimethylene trinitramine (RDX) bonded to hydroxyl-terminated polybutadiene (HTPB). We showed earlier that shock propagation from the high density RDX to the low density polymer (RDX ? Poly) across a nonplanar periodic interface (sawtooth) leads to a hotspot at the initial asperity but no additional hotspot at the second asperity. This hotspot arises from shear along the interface induced by relaxation of the stress at the asperity. We now report the case for shock propagation from the low density polymer to the high density RDX (Poly ? RDX) where we find a hotspot at the initial asperity and a second more dramatic hotspot at the second asperity. This second hotspot is enhanced due to shock wave convergence from shock wave interaction with nonplanar interfaces. We consider that this second hotspot is likely the source of the detonation in realistic PBX systems. We showed how these hotspots depend on the density mismatch between the RDX and polymer and found that decreasing the density by a factor of 2 dramatically reduces the hotspot. These results suggest that to make PBX less sensitive for propellants and explosives, the binder should be designed to provide low density at the asperity in contact with the RDX. Based on these simulations, we propose a new design for an insensitive PBX in which a low density polymer coating is deposited between the RDX and the usual polymer binder. To test this idea, we simulated shock wave propagation from two opposite directions (RDX ? Poly and Poly ? RDX) through the interface matched PBX (IM-PBX) material containing a 3 nm coating of low density (0.48 g/cm3) polymer. These simulations showed that this IM-PBX design dramatically suppresses hotspot formation

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

Dr Nicolaÿ : Illusions • Magie • Physique

Lithographie en couleur, 77 x 65 cmtéléchargeabl

Thaumaturgie humoristique par le Comte Patrizio de Castiglione : Folies-Bergère, tous les soirs

Lithographie en couleur, 90 x 66 cmtéléchargeabl

Dieback of fir in the Pyrenees in the Luchon region

Un phénomène de dépérissement se développe dans la sapinière des Pyrénées centrales, comparable par certains aspects à ce que l'on constate depuis quelques années dans les massifs forestiers vosgiens et allemands. Une étude phyto-écologique préalable du milieu (végétation, substrats, structure et dynamique forestière, climatologie) n'a révélé aucun déséquilibre majeur si ce n'est un vieillissement indéniable de certains peuplements et un développement abondant du gui et des lichens épiphytes. Une analyse détaillée des sols a fait apparaître l'existence de secteurs très oligotrophes sans qu'aucune corrélation avec l'état sanitaire des peuplements n'ait pu être mise en évidence. Les symptômes affectant le Sapin ainsi que le Hêtre sont décrits et l'importance spatiale du phénomène évaluée à l'aide de données du réseau DEFORPA. Deux hypothèses majeures sont ensuite étudiées : — existence d'une pollution fluorée : les teneurs foliaires mesurées ne sont pas négligeables (10 à 20 ppm) mais se situent nettement en dessous des seuils de nécrose ; — existence d'un phénomène de précipitations acides : des analyses d'eau de pluie en collecteur automatique révèlent une acidité importante (pH inférieur à 4,5 pour 85 % des échantillons) due essentiellement à la présence de deux anions majeurs SO4 et NO3. Des analyses foliaires montrent d'autre part chez les sapins dépérissants l'existence d'un déficit en calcium, d'une nette carence en potassium, d'une teneur en soufre supérieure à la moyenne généralement admise, ainsi qu'une chute sensible du taux de chlorophylle totale. Les auteurs concluent à l'existence en Luchonnais d'un double phénomène de dépérissement forestier et de précipitation acide, sans pour autant établir entre eux une relation de cause à effet.Dieback is spreading through the fir stands of the central Pyrenees, and is in some respects comparable to that observed for several years in the forests of the Vosges and Germany. A preliminary phytoecological study of the environment (vegetation, substrates, forest structure and dynamics, climatology) did not reveal any major imbalance apart from the undeniable aging of some stands and the abundant growth of mistletoe and epiphytic lichens. A detailed soil analysis revealed the existence of highly oligotrophic areas, although no correlation could be established with the state of health of the stands. The symptoms exhibited by firs and also beeches are described, and the size of the area affected by dieback is evaluated using data from the DEFORPA observation network. Two principal hypotheses are then studied : — the existence of fluoride pollution : the foliar levels measured are not inconsiderable (10 to 20 ppm), but are clearly below the thresholds for necrosis; — the existence of acid rain : analyses of rainwater gathered in an automatic collector show high acidity (ph inférieur à 4,5 for 85 % of the samples) due mainly to the presence of 2 major anions, SO4 and NO3. Foliar analyses of declining firs also show calcium deficiency, clear potassium deficiency, a higher sulphur content than average, as well as a perceptible drop in total chlorophyll content. The authors conclude that in the Luchon region both forest dieback and acid rain are occurring, although a cause-and-effect relationship cannot be established between them