Problem During pregnancy, the immune and the endocrine system cooperate to ensure that the fetal allograft develops without eliciting a maternal immune response. This is presumably in part achieved ...by dendritic cells (DCs) that play a dominant role in maintaining peripheral tolerance. In this study, we investigated whether female sex hormones, such as human chorionic gonadotropin (hCG), progesterone (Prog), and estradiol (E2), which are highly elevated during pregnancy, induce the differentiation of DCs into a tolerance‐inducing phenotype.
Methods/Results Immature DCs were generated from blood‐derived monocytes and differentiated in the presence of hCG, Prog, E2, or Dexamethasone (Dex) as a control. Unlike Dex, female sex hormones did not prevent the upregulation of surface markers characteristic for mature DCs, such as CD40, CD83, and CD86, except for hCG, which inhibited HLA‐DR expression. Similarly, hCG, Prog, and E2 had any impact on neither the rearrangement of the F‐actin cytoskeleton nor the enhanced chemokine secretion following DC maturation, both of which were strongly altered by Dex. Nevertheless, the T‐cell stimulatory capacity of DCs was significantly reduced after hCG and E2 exposure.
Conclusion Our findings suggest that the female sex hormones hCG and E2 inhibit the T‐cell stimulatory capacity of DCs, which may help in preventing an allogenic T‐cell response against the embryo.
Collaborative process modeling involves business analysts and subject matter experts in order to properly capture and document process knowledge. In this context, appropriate tool support is required ...to motivate these user groups to actively participate in collaborative process modeling. This paper presents a collaborative process modeling tool that enables the experts to create, visualize and evolve process models based on multi-touch devices (e.g., tablets and touch tables). In particular, users may edit process models on their tablets and share the created or changed process models with other team members on a common touch table. For this purpose, a sophisticated and intuitive interaction concept is provided. Furthermore, results of a controlled experiment, evaluating the influence the use of tablets has on collaborative process modeling based on touch tables, are presented. Altogether the experimental results emphasize the high potential of multi-touch tools for collaborative process modeling.
RAF expression in human astrocytic tumors Hagemann, Carsten; Gloger, Jens; Anacker, Jelena ...
International journal of molecular medicine,
01/2009, Letnik:
23, Številka:
1
Journal Article
Recenzirano
Odprti dostop
RAF proteins are well known oncoproteins. The B-RAF has been shown to be
activated by mutations in a multitude of human cancers. Alterations of C-RAF expression
are discussed to play a role in lung ...cancer. Only for A-RAF no link to tumorigenesis
has been published so far. Malignant gliomas are the most prevalent primary brain
tumors of adults. They are highly invasive and very difficult to treat, despite
of surgery, γ-irradiation and chemotherapy. Although a role of the mitogenic Ras-RAF-MEK-ERK
signalling cascade in brain tumor development is well established, there are only
few reports available addressing alterations in RAF sequence or protein expression
and function in human gliomas. We analysed the mutational status of A-RAF and
B-RAF in human glioblastomas (GBM) by sequencing. Then we checked for RAF gene
amplification by dot blot hybridization and examined RAF mRNA and protein expression
patterns in human astrocytic gliomas of WHO grade II (LGA) and IV (GBM) by semiquantitative
RT-PCR and Western blotting, respectively. The results were correlated with patients
prognosis. Finally, we performed functional assays to address a putative function
of A-RAF in glioma cell proliferation and migration. We showed that RAF mutations
are a rare event in glioblastoma multiforme. A-raf gene amplification was more
often detected and overexpression of all three RAF proteins on mRNA and protein
level was regularly found in human malignant gliomas. Whereas A-RAF and C-RAF
expression was negatively correlated with the patients prognosis, B-RAF expression
had a positive effect. Since neither A-RAF, nor C-RAF expression had any influence
on proliferation and migration of GBM cells, putative functions of C-RAF in angiogenesis
and of A-RAF in regulation of metabolism are discussed. Our data indicate that
RAF proteins might be valuable targets for small molecule therapies. However,
initially specific functions of RAF during tumorigenesis have to be elucidated.
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other ...psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10(-8)). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium-and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
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