Motif models proposing independent and interdependent impacts of nucleotides are related to high and low affinity transcription factor binding sites in Arabidopsis

Position weight matrix (PWM) is the traditional motif model representing the transcription factor (TF) binding sites. It proposes that the positions contribute independently to TFs binding affinity, although this hypothesis does not fit the data perfectly. This explains why PWM hits are missing in a substantial fraction of ChIP-seq peaks. To study various modes of the direct binding of plant TFs, we compiled the benchmark collection of 111 ChIP-seq datasets for Arabidopsis thaliana, and applied the traditional PWM, and two alternative motif models BaMM and SiteGA, proposing the dependencies of the positions. The variation in the stringency of the recognition thresholds for the models proposed that the hits of PWM, BaMM, and SiteGA models are associated with the sites of high/medium, any, and low affinity, respectively. At the medium recognition threshold, about 60% of ChIP-seq peaks contain PWM hits consisting of conserved core consensuses, while BaMM and SiteGA provide hits for an additional 15% of peaks in which a weaker core consensus is compensated through intra-motif dependencies. The presence/absence of these dependencies in the motifs of alternative/traditional models was confirmed by the dependency logo DepLogo visualizing the position-wise partitioning of the alignments of predicted sites. We exemplify the detailed analysis of ChIP-seq profiles for plant TFs CCA1, MYC2, and SEP3. Gene ontology (GO) enrichment analysis revealed that among the three motif models, the SiteGA had the highest portions of genes with the significantly enriched GO terms among all predicted genes. We showed that both alternative motif models provide for traditional PWM greater extensions in predicted sites for TFs MYC2/SEP3 with condition/tissue specific functions, compared to those for TF CCA1 with housekeeping functions. Overall, the combined application of standard and alternative motif models is beneficial to detect various modes of the direct TF-DNA interactions in the maximal portion of ChIP-seq loci

NPRD: Nucleosome Positioning Region Database

Nucleosome Positioning Region Database (NPRD), which is compiling the available experimental data on locations and characteristics of nucleosome formation sites (NFSs), is the first curated NFS-oriented database. The object of the database is a single NFS described in an individual entry. When annotating results of NFS experimental mapping, we pay special attention to several important functional characteristics, such as the relationship between type of gene activity and nucleosome positioning, the influence of non-histone proteins on nucleosome formation, type of the variant of nucleosome positioning (translational or rotational), indication of tissue types and states of cell activity, description of experimental methods used and accuracy of nucleosome position determination, and the results of applying theoretical and computer methods to the analysis of contextual and conformational DNA properties. At present, the NPRD database contains 438 entries and integrates the data described in 124 original papers. The database URL: http://srs6.bionet.nsc.ru/srs6/. Then click the button ‘Databank’ and open the link NUCLEOSOME

Epitope-dependent Selection of Highly Restricted or Diverse T Cell Receptor Repertoires in Response to Persistent Infection by Epstein-Barr Virus

The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11–restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. The response to the subdominant epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved Vβ usage and identical length and amino acid motifs in the third complementarity-determining regions (CDR3), while a broad repertoire using different combinations of TCR-α/β V and J segments and CDR3 regions was selected by the immunodominant epitope (EBNA4 416-424, designated IVT). Distinct patterns of interaction with the A11–peptide complex were revealed for each AVF- or IVT-specific TCR clonotype by alanine scanning mutagenesis analysis. Blocking of cytotoxic function by antibodies specific for the CD8 coreceptor indicated that, while AVF-specific TCRs are of high affinity, the oligoclonal response to the IVT epitope includes both low- and high-affinity TCRs. Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire

A Molecular Link between Malaria and Epstein–Barr Virus Reactivation

Although malaria and Epstein–Barr (EBV) infection are recognized cofactors in the genesis of endemic Burkitt lymphoma (BL), their relative contribution is not understood. BL, the most common paediatric cancer in equatorial Africa, is a high-grade B cell lymphoma characterized by c-myc translocation. EBV is a ubiquitous B lymphotropic virus that persists in a latent state after primary infection, and in Africa, most children have sero-converted by 3 y of age. Malaria infection profoundly affects the B cell compartment, inducing polyclonal activation and hyper-gammaglobulinemia. We recently identified the cystein-rich inter-domain region 1α (CIDR1α) of the Plasmodium falciparum membrane protein 1 as a polyclonal B cell activator that preferentially activates the memory compartment, where EBV is known to persist. Here, we have addressed the mechanisms of interaction between CIDR1α and EBV in the context of B cells. We show that CIDR1α binds to the EBV-positive B cell line Akata and increases the number of cells switching to the viral lytic cycle as measured by green fluorescent protein (GFP) expression driven by a lytic promoter. The virus production in CIDR1α-exposed cultures was directly proportional to the number of GFP-positive Akata cells (lytic EBV) and to the increased expression of the EBV lytic promoter BZLF1. Furthermore, CIDR1α stimulated the production of EBV in peripheral blood mononuclear cells derived from healthy donors and children with BL. Our results suggest that P. falciparum antigens such as CIDR1α can directly induce EBV reactivation during malaria infection that may increase the risk of BL development for children living in malaria-endemic areas. To our knowledge, this is the first report to show that a microbial protein can drive a latently infected B cell into EBV replication

High Catalytic Activity of Heterometallic (Fe6Na7 and Fe6Na6) Cage Silsesquioxanes in Oxidations with Peroxides

International audienceTwo types of heterometallic (Fe(III),Na) silsesquioxanes—[Ph5Si5O10]2[Ph10Si10O21]Fe6(O2‒)2Na7(H3O+)(MeOH)2(MeCN)4.5.1.25(MeCN), I, and [Ph5Si5O10]2[Ph4Si4O8]2Fe6Na6(O2‒)3(MeCN)8.5(H2O)8.44, II—were obtained and characterized. X-ray studies established distinctive structures of both products, with pair of Fe(III)-O-based triangles surrounded by siloxanolate ligands, giving fascinating cage architectures. Complex II proved to be catalytically active in the formation of amides from alcohols and amines, and thus becoming a rare example of metallasilsesquioxanes performing homogeneous catalysis. Benzene, cyclohexane, and other alkanes, as well as alcohols, can be oxidized in acetonitrile solution to phenol—the corresponding alkyl hydroperoxides and ketones, respectively—by hydrogen peroxide in air in the presence of catalytic amounts of complex II and trifluoroacetic acid. Thus, the cyclohexane oxidation at 20 °C gave oxygenates in very high yield of alkanes (48% based on alkane). The kinetic behaviour of the system indicates that the mechanism includes the formation of hydroxyl radicals generated from hydrogen peroxide in its interaction with di-iron species. The latter are formed via monomerization of starting hexairon complex with further dimerization of the monomer

Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions

<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-κB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p

Fatma Aliye and Defense of Islamic Values

The article concerns an analysis of the recently published text by Fatma Aliye debating with European ideas and prejudices about Islam that has not been a subject of interest in the South Slavonic intellectual and academic circles. Fatma Aliye (1862–1936) was the first Turkish woman novelist, the first Turkish woman philosopher, and the author of the book Tezâhür-i Hakikat (Appearance of Truth) that was published for the first time in January 2016 on the occasion of the 80th anniversary of her death. Like some writers of the Tanzimat era, especially Namik Kemal, Fatma Aliye entered the debate with the European writers wishing to oppose the prevailing Orientalist approach in Europe that had been blaming Islam for the stagnation of sciences and culture. She demonstrated enviable erudition and devotion to the Islamic culture. Her views show the permanent duality of the Ottoman intellectuals between their desire for Westernization and their need to stay in the Islamic tradition. In many aspects, the approaches to Islam and the defence of Islamic values of Fatma Aliye are still current