TGFβ1 Overexpression by Keratinocytes Alters Skin Dendritic Cell Homeostasis and Enhances Contact Hypersensitivity

Overexpression of transforming growth factor beta-1 (TGFβ1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGFβ1 overproduction by keratinocytes on skin dendritic cells (DCs). TGFβ1 induction for 2 and 4 days increased the numbers and CD86 expression of B220+ plasmacytoid DCs (pDCs) and CD207+CD103+, CD207−CD103−CD11b+, and CD207−CD103−CD11b− dermal DCs (dDCs) in skin-draining lymph nodes (SDLNs). The dermis of TGFβ1-overexpressing mice had significantly more pDCs, CD207+CD103+ dDCs, and CD207−CD11b+ dDCs in the absence of increased dermal proliferation. Application of dye, tetramethyl rhodamine iso-thiocyanate (TRITC), in dibutylpthalate (DBP) solution after TGFβ1 induction increased the numbers of TRITC+CD207− dDCs in SDLNs, and augmented TRITC/DBP-induced Langerhans cell (LC) migration 72hours post TRITC treatment. Consistent with this, LC migration was increased in vitro by TGFβ1 overexpression in skin explants and by exogenous TGFβ1 in culture media. Transient TGFβ1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGFβ1 alone is sufficient to alter homeostasis of multiple cutaneous DC subsets, and enhance DC migration and immune responses to contact sensitizers. These results highlight a role for keratinocyte-derived TGFβ1 in DC trafficking and in the initiation of skin inflammation

Mass Generation in Perturbed Massless Integrable Models

We extend form-factor perturbation theory to non--integrable deformations of massless integrable models, in order to address the problem of mass generation in such systems. With respect to the standard renormalisation group analysis this approach is more suitable for studying the particle content of the perturbed theory. Analogously to the massive case, interesting information can be obtained already at first order, such as the identification of the operators which create a mass gap and those which induce the confinement of the massless particles in the perturbed theory

Form-factors of the sausage model obtained with bootstrap fusion from sine-Gordon theory

We continue the investigation of massive integrable models by means of the bootstrap fusion procedure, started in our previous work on O(3) nonlinear sigma model. Using the analogy with SU(2) Thirring model and the O(3) nonlinear sigma model we prove a similar relation between sine-Gordon theory and a one-parameter deformation of the O(3) sigma model, the sausage model. This allows us to write down a free field representation for the Zamolodchikov-Faddeev algebra of the sausage model and to construct an integral representation for the generating functions of form-factors in this theory. We also clear up the origin of the singularities in the bootstrap construction and the reason for the problem with the kinematical poles.Comment: 16 pages, revtex; references added, some typos corrected. Accepted for publication in Physical Review

Ranging behaviour of translocated roe deer in a Mediterranean habitat: seasonal and altitudinal influences on home range size and patterns of range use

In this study we investigated the causes of seasonal variation in the home ranges of roe deer reintroduced to the Gardunha Mountains (Portugal). From May 2002 to April 2003, 1 year after the animals had been released, we collected data using radio-tracking techniques for five monitored animals (two males and three females). We found differences in the size of home ranges between seasons, with home ranges larger in summer than winter (minimum convex polygon peeled to 95%: summer 409.64 +/- 98.20 ha, winter 116.20 +/- 17.90 ha). This is contrary to evidence from central and northern Europe, where home ranges are typically larger in winter than summer. Moreover, two of the sampled females and one of the males tended to use higher elevations in summer. Comparisons between Mediterranean populations and those in central and northern Europe showed that Mediterranean populations in the winter easily fulfil their needs within a small area, whereas in the hot dry summer a larger area is needed. Furthermore, individuals prefer a higher, cooler mountainous habitat in summer, which is likely to be a means of avoiding warmer temperatures

Exact S-matrices for supersymmetric sigma models and the Potts model

We study the algebraic formulation of exact factorizable S-matrices for integrable two-dimensional field theories. We show that different formulations of the S-matrices for the Potts field theory are essentially equivalent, in the sense that they can be expressed in the same way as elements of the Temperley-Lieb algebra, in various representations. This enables us to construct the S-matrices for certain nonlinear sigma models that are invariant under the Lie ``supersymmetry'' algebras sl(m+n|n) (m=1,2; n>0), both for the bulk and for the boundary, simply by using another representation of the same algebra. These S-matrices represent the perturbation of the conformal theory at theta=pi by a small change in the topological angle theta. The m=1, n=1 theory has applications to the spin quantum Hall transition in disordered fermion systems. We also find S-matrices describing the flow from weak to strong coupling, both for theta=0 and theta=pi, in certain other supersymmetric sigma models.Comment: 32 pages, 8 figure

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field