A Series of Manganese(III) Salen Complexes as a Result of Team-Based Inquiry in a Transnational Education Programme.

The development of a team-based approach to research-led transnational practical chemistry teaching is described in which a team of five Chinese students on an articulated transnational degree programme, supported by a team of academic and technical staff, carried out a study examining the structural chemistry of a series of manganese(III) salen complexes. A series of four crystallographically characterized manganese(III) salen complexes with ancillary carboxylate ligands are reported here. The carboxylate coordination modes range from the bridging syn-anti μ2 -κO : κO' mode observed in the predominant cyclohexanoate and isobutyrate species, to a capping terminal monodentate mode for the adamantanoate species, and an unusual mixture of bridging and terminal coordination modes observed in a second minor phase of the cyclohexanoate species. The variation on extended structures based on the weakly interacting aliphatic backbones may provide a useful basis for further structural studies

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Replication Timing: A Fingerprint for Cell Identity and Pluripotency

Many types of epigenetic profiling have been used to classify stem cells, stages of cellular differentiation, and cancer subtypes. Existing methods focus on local chromatin features such as DNA methylation and histone modifications that require extensive analysis for genome-wide coverage. Replication timing has emerged as a highly stable cell type-specific epigenetic feature that is regulated at the megabase-level and is easily and comprehensively analyzed genome-wide. Here, we describe a cell classification method using 67 individual replication profiles from 34 mouse and human cell lines and stem cell-derived tissues, including new data for mesendoderm, definitive endoderm, mesoderm and smooth muscle. Using a Monte-Carlo approach for selecting features of replication profiles conserved in each cell type, we identify “replication timing fingerprints” unique to each cell type and apply a k nearest neighbor approach to predict known and unknown cell types. Our method correctly classifies 67/67 independent replication-timing profiles, including those derived from closely related intermediate stages. We also apply this method to derive fingerprints for pluripotency in human and mouse cells. Interestingly, the mouse pluripotency fingerprint overlaps almost completely with previously identified genomic segments that switch from early to late replication as pluripotency is lost. Thereafter, replication timing and transcription within these regions become difficult to reprogram back to pluripotency, suggesting these regions highlight an epigenetic barrier to reprogramming. In addition, the major histone cluster Hist1 consistently becomes later replicating in committed cell types, and several histone H1 genes in this cluster are downregulated during differentiation, suggesting a possible instrument for the chromatin compaction observed during differentiation. Finally, we demonstrate that unknown samples can be classified independently using site-specific PCR against fingerprint regions. In sum, replication fingerprints provide a comprehensive means for cell characterization and are a promising tool for identifying regions with cell type-specific organization

Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells

Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells

Substituent effects in the zinc(II) coordination chemistry of isomeric pyridylpyrazole ligands

Pyrazoles with unsymmetric substitution are useful ligands in coordination chemistry, but are under-developed due to synthetic challenges in accessing the pure isomers. We have prepared four new structurally related N-(2-pyridyl)-3,5-dialkylpyrazole ligands, L1-L4, and probed their coordination chemistry in the crystalline phase and in solution to elucidate a relationship between steric influence of the alkyl substituents, the stability of the subsequent metal complexes, and their crystal packing influences. We find that L1 and L2, bearing linear or branched alkyl substituents, show similar stabilities and crystal packing motifs featuring pi center dot center dot center dot pi and C-H center dot center dot center dot Cl interactions in the crystalline complexes 1 and 2, respectively. The cyclohexyl-fused species L3 and L4 vary both in the solution stability of complexes 3 and 4, respectively, and in their crystal packing. Complex [ZnCl2(L3)] (3) is a mononuclear complex similar to 1 and 2, albeit with pi center dot center dot center dot pi interactions disallowed by the bulk of the cyclohexyl ring. Reaction of isomeric L4 with ZnCl2 gives two polymorphic complexes, 4 alpha and 4 beta, of the form [Zn2Cl2(mu(2)-Cl)(2)(L4)(2)], varying only in their long-range packing modes. These results show the importance of understanding the steric influences in substituted pyridylpyrazoles, which determine both stability in solution and speciation in the crystalline phase

Supotsu to boken monogatari

<p><b>ITP results using the mean difference as test statistics for (A) recombination hotspots (localized differential landscape–LDL) and (B) mononucleotide microsatellites (invariant differential landscape–IDL) in the flanking regions of fixed ETn vs. controls.</b> The heatmap in the top panel shows the p-values for each component (i.e. window; horizontal axis) corrected controlling the family-wise error rate on all possible maximum interval lengths (vertical axis). Blue corresponds to low p-values, hence significant differences between the distributions underlying the flanking regions of ERVs and the controls. The middle panel shows corrected p-values at the chosen maximum interval length threshold, with gray highlighting significant components (corrected p-values<0.05). The lower panels show the average of the genome feature under consideration over the flanking regions of all fixed ETns (red line) and controls (green line). First and third quartiles (25% and 75% quantiles) are shaded in the respective colors–red for ETns and green for controls. The shades for control are invisible because they are zeros for control. The heatmap suggests the scales (vertical axis) and the locations (horizontal axis) at which the feature is significant to characterize ERVs genomic landscape.</p