25 research outputs found

    Orientability and energy minimization in liquid crystal models

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    Uniaxial nematic liquid crystals are modelled in the Oseen-Frank theory through a unit vector field nn. This theory has the apparent drawback that it does not respect the head-to-tail symmetry in which nn should be equivalent to -nn. This symmetry is preserved in the constrained Landau-de Gennes theory that works with the tensor Q=s(n⊗n−13Id)Q=s\big(n\otimes n- \frac{1}{3} Id\big).We study the differences and the overlaps between the two theories. These depend on the regularity class used as well as on the topology of the underlying domain. We show that for simply-connected domains and in the natural energy class W1,2W^{1,2} the two theories coincide, but otherwise there can be differences between the two theories, which we identify. In the case of planar domains we completely characterise the instances in which the predictions of the constrained Landau-de Gennes theory differ from those of the Oseen-Frank theory

    Stress-induced nuclear speckle reorganization is linked to activation of immediate early gene splicing

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    Current models posit that nuclear speckles (NSs) serve as reservoirs of splicing factors and facilitate posttranscriptional mRNA processing. Here, we discovered that ribotoxic stress induces a profound reorganization of NSs with enhanced recruitment of factors required for splice-site recognition, including the RNA-binding protein TIAR, U1 snRNP proteins and U2-associated factor 65, as well as serine 2 phosphorylated RNA polymerase II. NS reorganization relies on the stress-activated p38 mitogen-activated protein kinase (MAPK) pathway and coincides with splicing activation of both pre-existing and newly synthesized pre-mRNAs. In particular, ribotoxic stress causes targeted excision of retained introns from pre-mRNAs of immediate early genes (IEGs), whose transcription is induced during the stress response. Importantly, enhanced splicing of the IEGs ZFP36 and FOS is accompanied by relocalization of the corresponding nuclear mRNA foci to NSs. Our study reveals NSs as a dynamic compartment that is remodeled under stress conditions, whereby NSs appear to become sites of IEG transcription and efficient cotranscriptional splicing

    Transcriptional signature induced by a C-terminal c-Src mutant in a human breast cell line.

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    Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are characteristic of the viral oncogene protein v-Src and are present in some advanced human colon cancers. They are associated with increased kinase activity and elevated cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison to its wildtype protein, c-Src(wt), expressed in the human non-transformed breast epithelial cell line MCF-10A. We demonstrated previously that the mutant changed migratory and metastatic properties. Genome-wide transcriptome analysis revealed that c-Src(mt) deregulated the expression levels of about 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. More than 80% of these genes have previously been linked to cellular migration, while the others play roles, for instance, in RNA transport and splicing processes. Consistent with the transcriptome data, c-Src(mt)-, but not c-Src(wt)-expressing cells showed the capacity to metastasize into mouse lung tissue in vivo. The mRNA expression profile of c-Src(mt)-expressing cells shows significant overlap with that of various primary human tumor samples, perhaps reflecting elevated Src activity in some cancerous cells. Expression of c-Src(mt) lead to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. We identified genes and pathways deregulated by c-Src(mt) as biomarkers with potential interest for diagnostics or therapy of metastatic cells

    Epidemiological Profile Of 175 Patients With Crohn's Disease Submitted To Biological Therapy

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    Introduction: There is currently an increasing use of biological agents in the management of Crohn's disease (CD). There is lack of data regarding the epidemiological profile of patients on infliximab (IFX) and adalimumab (ADA) for CD in Brazil. Objective: To identify the epidemiological characteristics of patients with CD who underwent biological therapy. Method: Retrospective multicenter study, with CD patients on biological therapy. Analyzed variables: gender, age at treatment initiation, Montreal classification, concomitant perianal disease and smoking status. Results: 175 patients without previous exposure to biological agents were included, 93 (53%) were male. The mean age at treatment initiation was 35.5 (2-79) years old an the mean disease duration was 46.9 (0-480) months. Overall, 117 (66.9%) patients used IFX and 58 (33.1%), ADA. Montreal classification: age at diagnosis - A1 (n=21; 12%), A2 (n=102; 58.3%), and A3 (n=52; 29.7%). CD location - L1 (n=42; 24%), L2 (n=51; 29.1%), L3 (n=81; 46.3%), and L4 (n=1, 0.6%). Phenotype -B1 (n=59; 33.7%), B2 (n=46; 26.3%), and B3 (n=70; 40%). Perianal disease was found in 89 (50.9%) patients. Conclusions: The epidemiological profile of patients was similar to the literature. 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