The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances, manually curated from more than 2400 scientific publications. In addition, more data have been made available as individually searchable pages and are downloadable in various formats.

We are exploring the mechanisms underlying how maternal infection increases the risk for schizophrenia and autism in the offspring. Several mouse models of maternal immune activation (MIA) were used to examine the immediate effects of MIA induced by influenza virus, poly(I:C) and interleukin IL-6 on the fetal brain transcriptome. Our results indicate that all three MIA treatments lead to strong and common gene expression changes in the embryonic brain. Most notably, there is an acute and transient upregulation of the α, β and γ crystallin gene family. Furthermore, levels of crystallin gene expression are correlated with the severity of MIA as assessed by placental weight. The overall gene expression changes suggest that the response to MIA is a neuroprotective attempt by the developing brain to counteract environmental stress, but at a cost of disrupting typical neuronal differentiation and axonal growth. We propose that this cascade of events might parallel the mechanisms by which environmental insults contribute to the risk of neurodevelopmental disorders such as schizophrenia and autism.

Background Peripheral biomarkers for major psychiatric disorders have been an elusive target for the last half a century. Dermal fibroblasts are a simple, relevant, and much underutilized model for studying molecular processes of patients with affective disorders as they share considerable similarity of signal transduction with neuronal tissue. Methods Cultured dermal fibroblast samples from patients with Major Depressive Disorder (MDD) and matched controls (CNTR) (n=16 pairs, 32 samples) were assayed for genome wide mRNA expression using microarrays. In addition, a simultaneous qPCR-based assessment of >1,000 miRNA species was performed. Finally, to test the relationship between the mRNA-miRNA expression changes, the two datasets were correlated with each other. Results Our data revealed that MDD fibroblasts, when compared to matched controls, showed a strong mRNA gene expression pattern change in multiple molecular pathways, including cell-to-cell communication, innate/adaptive immunity and cell proliferation. Furthermore, the same patient fibroblasts showed altered expression of a distinct panel of 38 miRNAs, which putatively targeted many of the differentially expressed mRNAs. The miRNA-mRNA expression changes appeared to be functionally connected, as the majority of the miRNA and mRNA changes were in the opposite direction. Conclusions Our data suggest that a combined miRNA-mRNA assessments are informative about the disease process, and that analyses of dermal fibroblasts might lead to the discovery of promising peripheral biomarkers of MDD, which could be potentially used to aid the diagnosis and allow mechanistic testing of disturbed molecular pathways.