The photodecomposition product μ-oxalato-1κ^2O,O′:2κ^2O″,O‴-bis{bis[2-(2-pyridyl)phenyl-κ^2C,N]iridium(III)}–acetone (1/1.974)

An attempt to grow crystals of [Ir(ppy)_2(vacac)], (I), from an acetone-d_6 solution formed instead crystals of [{Ir(ppy)_2}_2(μ-oxalato)] acetone solvate, (II), [Ir_2(C_(11)H_8N)_4(C_2O_4)]·1.974C_3H_6O, where ppy is the phenyl­pyridine anion and vacac is vin­ylacetyl­acetonate. Each Ir^(III) ion in (II) is in a pseudo-octa­hedral coordination environment, where the pyridine N atoms are trans to each other and the phen­yl C atoms are trans to the O atoms of the oxalate bridging ligand. There are two crystallographically independent dimer molecules, each lying on an inversion centre. It is suggested that the oxalate ligand is formed in a series of steps initiated by the aldol condensation of acetone with vacac

Novel Modeling of Combinatorial miRNA Targeting Identifies SNP with Potential Role in Bone Density

MicroRNAs (miRNAs) are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting), a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD) in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential tool for miRNA-related studies. © 2012 Coronnello et al

clusterMaker: a multi-algorithm clustering plugin for Cytoscape

<p>Abstract</p> <p>Background</p> <p>In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present <it>clusterMaker</it>, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. <it>clusterMaker </it>is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL.</p> <p>Results</p> <p>Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast <it>Saccharomyces cerevisiae</it>; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section.</p> <p>Conclusions</p> <p>The Cytoscape plugin <it>clusterMaker </it>provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the <it>clusterMaker </it>plugin. <it>clusterMaker </it>is available via the Cytoscape plugin manager.</p

The Economies and Diseconomies of Industrial Clustering:Multinational Enterprises versus Uninational Enterprises

This study’s objective is to compare cluster economies and diseconomies for multinational enterprises (MNEs) and uninational enterprises (UNEs) within the London financial services cluster. In contrast to the implicit assumption of the cluster participation literature that the economies and diseconomies of clusters are valued similarly by all firms, we find that economies relating to social capital and labour market pooling are equally important to MNEs and UNEs, economies relating to local competition and diseconomies relating to congestion costs are more important to MNEs than to UNEs, and economies relating to the reputational effects of locating in a world-leading cluster and access to specialised suppliers are more important to UNEs than to MNEs. That MNEs and UNEs do not experience cluster economies and diseconomies in the same way indicates that both cluster participation theory and international business theory need augmentation to recognise that cluster incumbents benefit and suffer from cluster membership differently

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Vinigrol : a compact, Diene-Transmissive Diels-Alder strategy to the tricyclic core

A short (six steps from 17), versatile route to the tricyclic core of Vinigrol is described. A Lewis acid catalyzed and self-assembled Diels-Alder (LACASA-DA) reaction from the homoallylic cross-conjugated trienol 15 with N-methylmaleimide afforded the monoadduct 17 with diastereo-, regio-, and chemoselective control. Oxidation and installation of an acetylene (Ohira's reagent) followed by further manipulations afforded trienone 24. The second intramolecular Diels-Alder (at 45 C) reaction assembled the tricyclic skeleton 25 directly. The configuration of 25 was confirmed by X-ray analysis.NRC publication: Ye

Resorcinarene configuration and inclusion behaviour: isolation of a guest free form of pyrogall[4]arene

Both single crystals and bulk powder of the apo form of the rctt isomer of c-methylpyrogall[4]arene can be obtained, the former by molecular recognition in solution, the latter by desolvation of a clathrate.NRC publication: Ye

Pseudopolymorphism of ethylpyrogall[6]arene : investigating the role of solvent in guiding self-assembly of 3D networks

Recent studies have demonstrated that the r-tctct isomer of ethylpyrogall[6]arene (6EPGR) can be readily isolated as a minor product of the synthesis of the corresponding tetramer in the form of a 6 DMSO/1 6EPGR clathrate in the hexagonal space group R-3. Simultaneous studies in our group have led to the isolation of said hexamer as a 12 DMSO/1 6EPGR clathrate in the same space group. Using powder X-ray diffraction (PXRD) and 13C cross polarization magic angle spinning (CP/MAS) NMR spectroscopy, we have demonstrated that this 12 DMSO/1 6EPGR pseudopolymorph is, in fact, the precursor to the 6 DMSO/1 6EPGR form. The 6 DMSO/1 6EPGR form can be obtained through simple heating of this 12 DMSO/1 6EPGR precursor, as well as recrystallization of the precursor from acetone. Furthermore, in light of the data we have obtained using these techniques, in conjunction with direct observation of the process using a microscope, we suggest that the 6:1 inclusion as prepared by recrystallization from acetone is more appropriately modeled as containing acetone in addition to DMSO and comment on the relationship between these pseudopolymorphic forms and the impacts of the two methods of conversion on the structures of the clathrates.Peer reviewed: YesNRC publication: Ye