The role of IL-23 in the immunopathogenesis of psoriasis

In just 10 years from its discovery in 2000, interleukin-23 has quickly moved from being recognized as a pro-inflammatory cytokine to a key player and potential therapeutic target in psoriasis

Pinning of a solid--liquid--vapour interface by stripes of obstacles

We use a macroscopic Hamiltonian approach to study the pinning of a solid--liquid--vapour contact line on an array of equidistant stripes of obstacles perpendicular to the liquid. We propose an estimate of the density of pinning stripes for which collective pinning of the contact line happens. This estimate is shown to be in good agreement with Langevin equation simulation of the macroscopic Hamiltonian. Finally we introduce a 2--dimensional mean field theory which for small strength of the pinning stripes and for small capillary length gives an excellent description of the averaged height of the contact line.Comment: Plain tex, 12 pages, 3 figures available upon reques

Deformation and flow of a two-dimensional foam under continuous shear

We investigate the flow properties of a two-dimensional aqueous foam submitted to a quasistatic shear in a Couette geometry. A strong localization of the flow (shear banding) at the edge of the moving wall is evidenced, characterized by an exponential decay of the average tangential velocity. Moreover, the analysis of the rapid velocity fluctuations reveals self-similar dynamical structures consisting of clusters of bubbles rolling as rigid bodies. To relate the instantaneous (elastic) and time-averaged (plastic) components of the strain, we develop a stochastic model where irreversible rearrangements are activated by local stress fluctuations originating from the rubbing of the wall. This model gives a complete description of our observations and is also consistent with data obtained on granular shear bands by other groups.Comment: 5 pages, 2 figure

Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions

Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced the inflammatory response in the imiquimod-induced model of skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in particular keratinocytes, were responsible for this hyperinflammatory response, which involved upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders

Width distribution of contact lines on a disordered substrate

We have studied the roughness of a contact line of a liquid meniscus on a disordered substrate by measuring its width distribution. The comparison between the measured width distribution and the width distribution calculated in previous works, extended here to the case of open boundary conditions, confirms that the Joanny-de Gennes model is not sufficient to describe the dynamics of contact lines at the depinning threshold. This conclusion is in agreement with recent measurements which determine the roughness exponent by extrapolation to large system sizes.Comment: 4 pages, 3 figure

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Biodiversity and ecology of lichens of Katmai and Lake Clark National Parks and Preserves, Alaska

We inventoried lichens in Lake Clark (LACL) and Katmai (KATM) National Parks and Preserves. We assembled the known information on lichens in these parks by combining field, herbarium, and literature studies. Our results provide baseline data on lichen occurrence that may be used in resource condition assessments, vulnerability assessments, long-term ecological monitoring, and resource management. We report a total of 896 taxa of lichenized fungi from the Parks, adding 889 taxa to the total of seven taxa reported for the Parks by the National Park Service database and including ten new species first published elsewhere. An additional 15 lichenicolous fungi are reported here. Seven non-lichenized fungi associated with young living twigs of particular host species are also included. Sixteen species are new to Alaska, and six species new to North America (Caloplaca fuscorufa, Lecanora leucococca s.l., Ochrolechia brodoi, Protoparmelia memnonia, and Rhizocarpon leptolepis). Four new combinations are made, Cetraria minuscula, Enchylium millegranum var. bachmanianum, Lathagrium undulatum var. granulosum, and Protomicarea alpestris. Additional new species based on collections from the Parks have been described in separate publications