Foteini Christodoulou

Annelids and arthropods share a similar segmented organization of the body whose evolutionary origin remains unclear. The Hedgehog signaling pathway, prominent in arthropod embryonic segment patterning, has not been shown to have a similar function outside arthropods. We show that the ligand Hedgehog, the receptor Patched, and the transcription factor Gli are all expressed in striped patterns before the morphological appearance of segments in the annelid Platynereis dumerilii. Treatments with small molecules antagonistic to Hedgehog signaling disrupt segment formation. Platynereis Hedgehog is not necessary to establish early segment patterns but is required to maintain them. The molecular similarity of segment patterning functions of the Hedgehog pathway in an annelid and in arthropods supports a common origin of segmentation in protostomes.

Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined DEA of mRNAs and microRNAs (miRNAs) to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server uses as input miRNA/RNA-Seq read count data sets that can be uploaded for analysis. Users can combine their data with 350 small-RNA-Seq and 65 RNA-Seq in-house analyzed libraries which are provided by DIANA-mirExTra v2.0.The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets. More than 450 000 miRNA interactions and 2 000 000 TF binding sites from specific or high-throughput techniques have been incorporated, while accurate miRNA TSS annotation is obtained from microTSS experimental/in silico framework. These comprehensive data sets enable users to perform analyses based solely on experimentally supported information and to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression. The server also supports predicted miRNA:gene interactions from DIANA-microT-CDS for 4 species (human, mouse, nematode and fruit fly). DIANA-mirExTra v2.0 has an intuitive user interface and is freely available to all users without any login requirement.

Binding of podoplanin to the C-type lectin-like receptor 2 (CLEC-2) promotes platelet activation and soluble CLEC-2 (sCLEC-2) is shed from activated platelets. The role of sCLEC-2 in the plasma is unknown. The expression level and plasma concentration of sCLEC-2 could be affected by variants of the corresponding gene, CLEC1B. Here, we genotyped SNVs in the promoter and coding region of CLEC1B and determined plasma levels of sCLEC-2 in healthy individuals. We genotyped 516 healthy blood donors for 7 SNVs (rs10505743, rs11053538, rs4764178, rs76016091, rs2273986, rs2273987, rs521040) by using PCR methods and calculated haplotypes from the SNV genotypes. For 313 of the donors we measured the sCLEC-2 concentration in EDTA plasma samples by using a commercial ELISA. SNV typing revealed allele frequencies comparable to database information. None of the SNVs showed significant correlation with sCLEC-2 plasma levels. Haplotype analysis indicated 6 haplotypes with frequencies >1% and haplotype h3 was the most frequent (33.8%). Donors homozygous for h3 (n = 37) showed significantly lower sCLEC-2 plasma levels (median 0.95 ng/mL) than donors being h3 negative or heterozygous (n = 276; 1.44 ng/mL; p = .0203). We found that the sCLEC-2 plasma concentration is variable in healthy individuals and the CLEC1B genotype contributes to the expression level.