Ageing: collagenase‐mediated collagen fragmentation as a rejuvenation target

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108666/1/bjd13267.pd

Severe disruption and disorganization of dermal collagen fibrils in early striae gravidarum

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142909/1/bjd15895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142909/2/bjd15895_am.pd

Phase-Field Approach for Faceted Solidification

We extend the phase-field approach to model the solidification of faceted materials. Our approach consists of using an approximate gamma-plot with rounded cusps that can approach arbitrarily closely the true gamma-plot with sharp cusps that correspond to faceted orientations. The phase-field equations are solved in the thin-interface limit with local equilibrium at the solid-liquid interface [A. Karma and W.-J. Rappel, Phys. Rev. E53, R3017 (1996)]. The convergence of our approach is first demonstrated for equilibrium shapes. The growth of faceted needle crystals in an undercooled melt is then studied as a function of undercooling and the cusp amplitude delta for a gamma-plot of the form 1+delta(|sin(theta)|+|cos(theta)|). The phase-field results are consistent with the scaling law "Lambda inversely proportional to the square root of V" observed experimentally, where Lambda is the facet length and V is the growth rate. In addition, the variation of V and Lambda with delta is found to be reasonably well predicted by an approximate sharp-interface analytical theory that includes capillary effects and assumes circular and parabolic forms for the front and trailing rough parts of the needle crystal, respectively.Comment: 1O pages, 2 tables, 17 figure

Genetic associations of psoriasis in a Pakistani population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99639/1/bjd12313.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99639/2/bjd12313-sup-0001-TableS1-S2.pd

Electrovacuum Static Counterrotating Relativistic Dust Disks

A detailed study is presented of the counterrotating model (CRM) for generic electrovacuum static axially symmetric relativistic thin disks without radial pressure. We find a general constraint over the counterrotating tangential velocities needed to cast the surface energy-momentum tensor of the disk as the superposition of two counterrotating charged dust fluids. We also find explicit expressions for the energy densities, charge densities and velocities of the counterrotating fluids. We then show that this constraint can be satisfied if we take the two counterrotating streams as circulating along electro-geodesics. However, we show that, in general, it is not possible to take the two counterrotating fluids as circulating along electro-geodesics nor take the two counterrotating tangential velocities as equal and opposite. Four simple families of models of counterrotating charged disks based on Chazy-Curzon-like, Zipoy-Voorhees-like, Bonnor-Sackfield-like and Kerr-like electrovacuum solutions are considered where we obtain some disks with a CRM well behaved. The models are constructed using the well-known ``displace, cut and reflect'' method extended to solutions of vacuum Einstein-Maxwell equations.Comment: 19 pages, 16 figures, revtex

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10−89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton’s tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS

Retinoic acid induction of human cellular retinoic acid-binding protein-II gene transcription is mediated by retinoic acid receptor-retinoid X receptor heterodimers bound to one far upstream retinoic acid-responsive element with 5-base pair spacing.

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