59 research outputs found
Simulating psoriasis by altering transit amplifying cells
No full textComputational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (tau). Prolonging tau results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells and (4) a marked reduction in turnover time. The prolongation of tau is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency
A multicellular systems biology model predicts epidermal morphology, kinetics and Ca2+ flow
No full textSystems biology is currently focused on integrating intracellular networks, although clinically, diseases are largely defined by their histological features. For example, no computational model can simulate today the formation of a horizontally layered epidermis. Since the epidermis is the most complex structured epithelial tissue, systems biology models could yield important insights in epithelial tissue, in which most of all human cancers arise
Neuber K: Simulating psoriasis by altering transit amplifying cells
No full textComputational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in-silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (τ). Prolonging τ results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells, and (4) a marked reduction in turnover time. The prolongation of τ is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency. Contact
ESR4: Palaeography and digital scholarly editions
No full textMy name is Frederike Neuber, I’m originally from Germany and I’m currently based at the University of Graz at the Austrian Centre for Digital Humanities (Centre for Information Modelling). My supervisor is Georg Vogeler. I graduated in March 2014 at Freie Universität Berlin in ‘Editionwissenschaft’, which is something in between Editorial Philology and Textual Scholarship. My master’s thesis was a scholarly edition of a collection of letters from the german author Fanny Lewald (1811-1889) to ..
The relevance of transthyretin and hsp 27 in the aging skin
No full textDer Alterungsprozess der Haut zeigt sich vor allem in dem Abbau der dermalen Matrixproteine im Bereich der Dermis, welche schließlich als Faltenbildung sichtbar werden. Über die eigentliche ‘äußere Schicht’ des Körpers, die Epidermis, welche zum größten Teil aus Keratinozyten besteht, sind kaum Alterungsmechanismen bekannt.
In dieser Arbeit konnten Proteine aus Spalthäuten als Epidermisäquivalent mittels zweidimensionaler Gelelektrophorese dargestellt werden. Im Vergleich von jungen zu älteren Spalthautspendern konnte festgestellt werden, dass es zu altersabhängigen Proteinveränderungen kommt. Dazu zählen unter anderem das kleine Hitzeschockprotein HSP 27 sowie das Plasmaprotein Transthyretin, die mittels MALDI-Q-TOF identifiziert und anschließend über Western Blot Verfahren verifiziert wurden. Transthyretin scheint nicht in der Epidermis synthetisiert zu werden, allerdings scheint es als Transportprotein für ihre intakte Funktion unerlässlich.
HSP 27 scheint ein Marker für den Stresszustand der Haut darzustellen. Dabei ist auffällig, dass es in gealterter Haut ungleichmäßig exprimiert wird, sich dann allerdings mit deutlich zunehmendem Alter eine verringerte Expression zeigt. Ursächlich für eine verstärkte Expression scheint ein erhöhter Stresszustand bei gleichzeitig differenzierten Keratinozyten zu sein, da HSP 27 überwiegend in suprabasalen Zelllagen der Epidermis exprimiert wird. Neben einem ungestressten Zustand der Keratinozyten im Alter kann auch eine Reduktion der Epidermisschichten im Alter ursächlich sein für eine reduzierte HSP 27 Expression. Andererseits kann aber auch eine altersabhängige Zunahme von funktionslosen oder denaturierten Proteinen, die nachfolgend die Transkription von Hitzeschock-Proteinen negativ beeinflussen, eine reduzierte HSP 27 Expression zur Folge haben. Mit den fehlenden protektiven Funktionen des kleinen Hitzeschockproteins könnte dies auch ein erhöhtes Neoplasierisiko im Alter bedeuten
Treosulfan in the Treatment of Metastatic Melanoma: From Chemosensitivity Testing to Clinical Trials
No full textTotal and specific serum IgE decreases with age in patients with allergic rhinitis, asthma and insect allergy but not in patients with atopic dermatitis
No full textAbstract Concerning allergic diseases, the incidence of allergic symptoms, as well as their severity, seems to decrease with age. The decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total and specific IgE. Atopic disorders are complex diseases that involve interactions among several physiological systems, e.g. skin, lung, mucosae, and the immune system. It was the aim of this study to compare the effects of age on total and specific IgE in patients with atopic dermatitis (AD), allergic rhinitis or asthma, and insect allergy, respectively. The study population consisted of 559 individuals (male: 229 and female: 330). Total and allergen specific IgE was measured in every individual. From the whole study population, 113 patients suffered from atopic dermatitis (AD), 132 had allergic rhinitis or asthma, and 314 were tested because of insect allergy. Total and specific serum IgE was significantly decreased as a function of age in patients with allergic rhinitis and asthma and with insect allergy. In contrast, no significant decrease of total and specific serum IgE in old individuals with AD was observed. Additionally, in the group of patients with a total IgE 300 kU/l showed no correlation with age. Immunosenescence does not affect increased IgE levels in atopic patients with AD and/or high serum IgE levels indicating that in these subgroups of patients the atopic propensity remains into advanced age. One may hypothesize that either onset of allergic sensitization during life or the kind of atopic disease influences the correlation between age and IgE synthesis.</p
Expression of Fas Ligand (CD95L) in Primary Malignant Melanoma and Melanoma Metastases is Associated with Overall Survival
No full textBIOINFORMATICS DISCOVERY NOTE doi:10.1093/bioinformatics/btm042 Systems biology Simulating psoriasis by altering transit amplifying cells
No full textComputational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (). Prolonging results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells and (4) a marked reduction in turnover time. The prolongation of is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency. Contact
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