Drm/Gremlin and Dan, two homologous secreted antagonists of bone morphogenic proteins, have been shown to regulate early development, tumorigenesis, and renal pathophysiology. In this study, we report that Drm and Dan physically and functionally interact with Slit1 and Slit2 proteins. Drm binding to Slits depends on its glycosylation and is not interfered with by bone morphogenic proteins. Importantly, Drm and Dan function as inhibitors for monocyte migration induced by stromal cell-derived factor 1α (SDF-1α) or fMLP. The inhibition of SDF-1α-induced monocyte chemotaxis by Dan is not due to blocking the binding of SDF-1α to its receptor. Thus, the results identify that Drm and Dan can interact with Slit proteins and act as inhibitors of monocyte chemotaxis, demonstrating a previously unidentified biological role for these proteins.

In crosses of wild and cultivated peas (Pisum sativum L.), nuclear-cytoplasmic incompatibility frequently occurs manifested as decreased pollen fertility, male gametophyte lethality, sporophyte lethality. High-throughput sequencing of plastid genomes of one cultivated and four wild pea accessions differing in cross-compatibility was performed. Candidate genes for involvement in the nuclear-plastid conflict were searched in the reconstructed plastid genomes. In the annotated Medicago truncatula genome, nuclear candidate genes were searched in the portion syntenic to the pea chromosome region known to harbor a locus involved in the conflict. In the plastid genomes, a substantial variability of the accD locus represented by nucleotide substitutions and indels was found to correspond to the pattern of cross-compatibility among the accessions analyzed. Amino acid substitutions in the polypeptides encoded by the alleles of a nuclear locus, designated as Bccp3, with a complementary function to accD, fitted the compatibility pattern. The accD locus in the plastid genome encoding beta subunit of the carboxyltransferase of acetyl-coA carboxylase and the nuclear locus Bccp3 encoding biotin carboxyl carrier protein of the same multi-subunit enzyme were nominated as candidate genes for main contribution to nuclear-cytoplasmic incompatibility in peas. Existence of another nuclear locus involved in the accD-mediated conflict is hypothesized.

Since the human genome was sequenced in draft, single nucleotide polymorphism (SNP) analysis has become one of the keynote fields of bioinformatics. We have developed an integrated database-tools system, rSNP_Guide (http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/), devoted to prediction of transcription factor (TF) binding sites, alterations of which could be associated with disease phenotype. By inputting data on alterations in DNA sequence and in DNA binding pattern of an unknown TF, rSNP_Guide searches for a known TF with alterations in the recognition score calculated on the basis of TF site's sequence and consistent with the input alterations in DNA binding to the unknown TF. Our system has been tested on many relationships between known TF sites and diseases, as well as on site-directed mutagenesis data. Experimental verification of rSNP_Guide system was made on functionally important SNPs in human TDO2and mouse K-ras genes. Additional examples of analysis are reported involving variants in the human gammaA-globin (HBG1), hsp70(HSPA1A), and Factor IX (F9) gene promoters.

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Fragments of rRNA, mitochondrial transcripts, microRNAs, fragments of scRNAs, snRNA and snoRNA, fragments of several mRNAs as well as the set of newly discovered transcripts were found to be permanent representatives of human blood plasma RNAs. Advanced mapping allowed to identify circulating herpes virus and enterobacterial transcripts. Documented profile of circulating RNA of healthy individuals provides basis for development of new approaches in research and diagnosis of human pathology.

Single base mutations GC CA at position 663 and GC CT at position 666 of intron 6 of the human tryptophan oxygenase gene (TDO2) are associated with a variety of psychiatric disorders [Comings, D.E. et al. (1996) Pharmacogenetics 6, 307^318]. Binding of rat liver nuclear extract proteins to synthetic double-strand oligonucleotides corresponding to three allelic states of the region between 651 bp and 680 bp of human TDO2 intron 6 has been studied by gel shift assay. It has been demonstrated that to each allelic state of the region there corresponds a specific set of proteins that interacts with it. With the aid of computer analysis and using specific anti-YY-1 antibodies it has been shown that both mutations damage the YY-1 transcription factor binding site.z 1999 Federation of European Biochemical Societies.

Auxin plays a pivotal role in virtually every aspect of plant morphogenesis. It simultaneously orchestrates a diverse variety of processes such as cell wall biogenesis, transition through the cell cycle, or metabolism of a wide range of chemical substances. The coordination principles for such a complex orchestration are poorly understood at the systems level. Here, we perform an RNA-seq experiment to study the transcriptional response to auxin treatment  within gene groups of different biological processes, molecular functions, or cell components in a quantitative fold-change-specific manner. We find for Arabidopsis thaliana roots treated with auxin for 6 h that (i) there are functional groups within which genes respond to auxin with a surprisingly similar fold changes and that (ii) these fold changes vary from one group to another. These findings make it tempting to conjecture the existence of some transcriptional logic orchestrating the coordinated expression of genes within functional groups in a fold-change-specific manner. To obtain some initial insight about this coordinated expression, we performed a motif enrichment analysis and found cis-regulatory elements TBX1-3, SBX, REG, and TCP/site2 as the candidates conferring fold-change-specific responses to auxin in Arabidopsis thaliana.

Background In population ecology, the concept of reproductive potential denotes the most vital indicator of chances to produce and sustain a healthy descendant until his/her reproductive maturity under the best conditions. This concept links quality of life and longevity of an individual with disease susceptibilities encoded by his/her genome. Female reproductive potential has been investigated deeply, widely, and comprehensively in the past, but the male one has not received an equal amount of attention. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of male reproductive potential. Results Examining in silico (i.e., using our earlier created Web-service SNP_TATA_Z-tester) all 1206 unannotated SNPs within 70 bp proximal promoters of all 63 Y-linked genes, we found 261 possible male-reproductive-potential SNP markers that can significantly alter the binding affinity of TATA-binding protein (TBP) for these promoters. Among them, there are candidate SNP markers of spermatogenesis disorders (e.g., rs1402972626), pediatric cancer (e.g., rs1483581212) as well as male anxiety damaging family relationships and mother’s and children’s health (e.g., rs187456378). First of all, we selectively verified in vitro both absolute and relative values of the analyzed TBP–promoter affinity, whose Pearson’s coefficients of correlation between predicted and measured values were r = 0.84 (significance p <  0.025) and r = 0.98 (p <  0.025), respectively. Next, we found that there are twofold fewer candidate SNP markers decreasing TBP–promoter affinity relative to those increasing it, whereas in the genome-wide norm, SNP-induced damage to TBP–promoter complexes is fourfold more frequent than SNP-induced improvement (p <  0.05, binomial distribution). This means natural selection against underexpression of these genes. Meanwhile, the numbers of candidate SNP markers of an increase and decrease in male reproductive potential were indistinguishably equal to each other (p <  0.05) as if male self-domestication could have happened, with its experimentally known disruptive natural selection. Because there is still not enough scientific evidence that this could have happened, we discuss the human diseases associated with candidate SNP markers of male reproductive potential that may correspond to domestication-related disorders in pets. Conclusions Overall, our findings seem to support a self-domestication syndrome with disruptive natural selection by male reproductive potential preventing Y-linked underexpression of a protein.