A Turing mechanism in order to explain the patchy nature of Crohn's disease.

Crohn's disease is an inflammatory bowel disease (IBD) that is not well understood. In particular, unlike other IBDs, the inflamed parts of the intestine compromise deep layers of the tissue and are not continuous but separated and distributed through the whole gastrointestinal tract, displaying a patchy inflammatory pattern. In the present paper, we introduce a toy-model which might explain the appearance of such patterns. We consider a reaction-diffusion system involving bacteria and phagocyte and prove that, under certain conditions, this system might reproduce an activator-inhibitor dynamic leading to the occurrence of Turing-type instabilities. In other words, we prove the existence of stable stationary solutions that are spatially periodic and do not vanish in time. We also propose a set of parameters for which the system exhibits such phenomena and compare it with realistic parameters found in the literature. This is the first time, as far as we know, that a Turing pattern is investigated in inflammatory models.

Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status.

The conditions used to describe the presence of an immune disease are often represented by interaction graphs. These informative, but intricate structures are susceptible to perturbations at different levels. The mode in which that perturbation occurs is still of utmost importance in areas such as cell reprogramming and therapeutics models. In this sense, module identification can be useful to well characterise the global graph architecture. To help us with this identification, we perform topological overlap-related measures. Thanks to these measures, the location of highly disease-specific module regulators is possible. Such regulators can perturb other nodes, potentially causing the entire system to change behaviour or collapse. We provide a geometric framework explaining such situations in the context of inflammatory bowel diseases (IBD). IBD are severe chronic disorders of the gastrointestinal tract whose incidence is dramatically increasing worldwide. Our approach models different IBD status as Riemannian manifolds defined by the graph Laplacian of two high throughput proteome screenings. It also identifies module regulators as singularities within the manifolds (the so-called singular manifolds). Furthermore, it reinterprets the characteristic nonlinear dynamics of IBD as compensatory responses to perturbations on those singularities. Then, particular reconfigurations of the immune system could make the disease status move towards an innocuous target state.

Refined Regularity of the Blow-Up Set Linked to Refined Asymptotic Behavior for the Semilinear Heat Equation.

We consider u ⁢ ( x , t ) , a solution of ∂ t ⁡ u = Δ â¢ u + | u | p - 1 ⁢ u which blows up at some time T > 0 , where u : ℝ N × [ 0 , T ) → ℝ , p > 1 and ( N - 2 ) ⁢ p < N + 2 . Define S ⊂ ℝ N to be the blow-up set of u, that is, the set of all blow-up points. Under suitable non-degeneracy conditions, we show that if S contains an ( N - ℓ ) -dimensional continuum for some ℓ ∈ { 1 , … , N - 1 } , then S is in fact a 𝒞 2 manifold. The crucial step is to make a refined study of the asymptotic behavior of u near blow-up. In order to make such a refined study, we have to abandon the explicit profile function as a first-order approximation and take a non-explicit function as a first-order description of the singular behavior. This way we escape logarithmic scales of the variable ( T - t ) and reach significant small terms in the polynomial order ( T - t ) µ for some µ > 0 . Knowing the refined asymptotic behavior yields geometric constraints of the blow-up set, leading to more regularity on S.

Integrative Network-based Analysis of Colonic Detoxification Gene Expression in Ulcerative Colitis According to Smoking Status.

BACKGROUNDS AND AIMS: The effect of cigarette smoking [CS] is ambivalent since smoking improves ulcerative colitis [UC] while it worsens Crohn's disease [CD]. Although this clinical relationship between inflammatory bowel disease [IBD] and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes. METHODS: A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers [n = 8] and non-smokers [n = 9] versus the non-affected colonic mucosa of UC patients [n = 19] was performed by quantitative real-time polymerase chain reaction [qRT PCR]. The detoxification gene expression profile was analysed in CD patients [n = 18], in smoking UC patients [n = 5], and in biopsies from non-smoking UC patients cultured or not with cigarette smoke extract [n = 8]. RESULTS: Of the 244 detoxification genes investigated, 65 were dysregulated in UC patients in comparison with healthy controls or CD patients. The expression of ≥ 45/65 genes was inversed by CS in biopsies of smoking UC patients in remission and in colonic explants of UC patients exposed to cigarette smoke extract. We devised a network-based data analysis approach for differentially assessing changes in genetic interactions, allowing identification of unexpected regulatory detoxification genes that may play a major role in the beneficial effect of smoking on UC. CONCLUSIONS: Non-inflamed colonic mucosa in UC is characterised by a specifically altered detoxification gene network, which is partially restored by tobacco. These mucosal signatures could be useful for developing new therapeutic strategies and biomarkers of drug response in UC.