Psoriasis: Molecular targets of denervation and therapy

In this thesis global transcriptomic effects of denervation were analyzed in unique cases showing unilateral resolution of psoriasis occurred following surgical denervation (chapter 2). In our studies, we focused on the epidermis, as this forms the main innate defence barrier of the skin. We analysed global transcriptomic effects of surgical denervation in a murine psoriasiform model (chapter 3). Because the contribution of neuromediators to innate defence is mostly unknown, we investigated the effects of SP, CGRP, and VIP on the epidermal expression of TLR and host defence peptides in an ex vivo skin explant model (chapter 4). The molecular epidermal targets of recombinant IL-4 in ex vivo stimulated biopsies from psoriatic and healthy skin were investigated (chapter 5). Furthermore, the effect of the biologic ustekinumab (anti IL-12/IL-23) on epidermal molecular markers of innate defence in uninvolved skin of patients with psoriasis was investigated (chapter 6). The following main conclusions were drawn: Denervation affected genes involved in epidermal barrier function, and TLR function, as the inflammatory response to the TLR7 ligand imiquimod is prevented in denervated skin. Denervation inhibited cutaneous CGRP expression and prevented the enhanced expression of CGRP by imiquimod. Ex vivo stimulation of skin with GCRP results in enhanced expression of epidermal TLR9. Established treatments reach beyond the dermal infiltrate and also target keratinocytes: IL-4 and ustekinumab therapy increase GATA3, which is a transcription factor critical for epidermal homeostasis, and down-regulate NGF expression, which is linked to inflammatory conditions

Community structure and ethnic preferences in school friendship networks

Recently developed concepts and techniques of analyzing complex systems provide new insight into the structure of social networks. Uncovering recurrent preferences and organizational principles in such networks is a key issue to characterize them. We investigate school friendship networks from the Add Health database. Applying threshold analysis, we find that the friendship networks do not form a single connected component through mutual strong nominations within a school, while under weaker conditions such interconnectedness is present. We extract the networks of overlapping communities at the schools (c-networks) and find that they are scale free and disassortative in contrast to the direct friendship networks, which have an exponential degree distribution and are assortative. Based on the network analysis we study the ethnic preferences in friendship selection. The clique percolation method we use reveals that when in minority, the students tend to build more densely interconnected groups of friends. We also find an asymmetry in the behavior of black minorities in a white majority as compared to that of white minorities in a black majority.Comment: submitted to Physica

Why and how selection patterns in classroom networks differ between students : the potential influence of networks size preferences, level of information, and group membership

Los estudiantes de secundaria pueden escoger compañeros como nuevos amigos utilizando un repertorio de modalidades. Pueden querer activamente crear nuevas amistades, utilizar la estructura existente de la red y/o utilizar la información, escasa y a menudo errónea, sobre los "candidatos". En este artículo teórico argumentamos que dichas modalidades de selección no deben ser estudiadas como resultado de reglas generales tal y como se viene haciendo en los estudios sobre redes sociales. En concreto, afirmamos que las preferencias relativas al tamaño de las redes, el nivel de información sobre los atributos de los compañeros de clase y la pertenencia a grupos pueden ser distintas para cada alumno y, por ello, también sus modalidalidades de selección pueden ser distintas. En este artíclo se esbozan las articulaciones teóricas entre ellos.High school students can select class mates for new friendships using a repertoire of patterns. They can actively pursue new friendships, make use of the existing network structure, and/ or use the scarce and often erroneous information about candidates. In this theoretical paper, we argue that such selection patterns should not be studied as the result of general rules, as is usually done in social network studies. Specifically, we state that network size preferences, the level of information about individual attributes of fellow classmates, and group membership are likely to differ among high school students, and that as a result, also their selection patterns are likely to be different. In this paper we sketch the theoretical articulations between these

Cómo y por qué los modelos de selección difieren entre estudiantes. La influencia potencial de los tamaños de la red, el nivel de información y la pertenencia a grupos

High school students can select class mates for new friendships using a repertoire of patterns. They can actively pursue new friendships, make use of the existing network structure, and/ or use the scarce and often erroneous information about candidates. In this theoretical paper, we argue that such selection patterns should not be studied as the result of general rules, as is usually done in social network studies. Specifically, we state that network size preferences, the level of information about individual attributes of fellow classmates, and group membership are likely to differ among high school students, and that as a result, also their selection patterns are likely to be different. In this paper we sketch the theoretical articulations between these.Los estudiantes de secundaria pueden escoger compañeros como nuevos amigos utilizando un repertorio de modalidades. Pueden querer activamente crear nuevas amistades, utilizar la estructura existente de la red y/o utilizar la información, escasa y a menudo errónea, sobre los “candidatos”. En este artículo teórico argumentamos que dichas modalidades de selección no deben ser estudiadas como resultado de reglas generales tal y como se viene haciendo en los estudios sobre redes sociales. En concreto, afirmamos que las preferencias relativas al tamaño de las redes, el nivel de información sobre los atributos de los compañeros de clase y la pertenencia a grupos pueden ser distintas para cada alumno y, por ello, también sus modalidalidades de selección pueden ser distintas. En este artíclo se esbozan las articulaciones teóricas entre ellos