Accessing rare α-heterocyclic aziridines via Brønsted acid-catalyzed Michael addition/annulation : scope, limitations, and mechanism

Funding: T.A.H. thanks the University of St Andrews for a PhD studentship. A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF-2022-014).We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Brønsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presentedPeer reviewe

Lunar mineral feedstocks from rocks and soils: X-ray digital imaging in resource evaluation

The rocks and soils of the Moon provide raw materials essential to the successful establishment of a lunar base. Efficient exploitation of these resources requires accurate characterization of mineral abundances, sizes/shapes, and association of 'ore' and 'gangue' phases, as well as the technology to generate high-yield/high-grade feedstocks. Only recently have x-ray mapping and digital imaging techniques been applied to lunar resource evaluation. The topics covered include inherent differences between lunar basalts and soils and quantitative comparison of rock-derived and soil-derived ilmenite concentrates. It is concluded that x-ray digital-imaging characterization of lunar raw materials provides a quantitative comparison that is unattainable by traditional petrographic techniques. These data are necessary for accurately determining mineral distributions of soil and crushed rock material. Application of these techniques will provide an important link to choosing the best raw material for mineral beneficiation

Cross Sectional Investigation of Coxiella burnetii Following Parturition: A New Spotlight on a Neglected Zoonotic Disease in Scotland

No abstract available

Performance and Simulation of the RICE detector

The RICE experiment (Radio Ice Cherenkov Experiment) at the South Pole, co-deployed with the AMANDA experiment, seeks to detect ultra-high energy (UHE) electron neutrinos interacting in cold polar ice. Such interactions produce electromagnetic showers, which emit radio-frequency Cherenkov radiation. We describe the experimental apparatus and the procedures used to measure the neutrino flux.Comment: preprint, to be submitted to Astropart. Phy

High-Throughput In Vivo Analysis of Gene Expression in Caenorhabditis elegans

Using DNA sequences 5′ to open reading frames, we have constructed green fluorescent protein (GFP) fusions and generated spatial and temporal tissue expression profiles for 1,886 specific genes in the nematode Caenorhabditis elegans. This effort encompasses about 10% of all genes identified in this organism. GFP-expressing wild-type animals were analyzed at each stage of development from embryo to adult. We have identified 5′ DNA regions regulating expression at all developmental stages and in 38 different cell and tissue types in this organism. Among the regulatory regions identified are sequences that regulate expression in all cells, in specific tissues, in combinations of tissues, and in single cells. Most of the genes we have examined in C. elegans have human orthologs. All the images and expression pattern data generated by this project are available at WormAtlas (http://gfpweb.aecom.yu.edu/index) and through WormBase (http://www.wormbase.org)

A Transcription Factor Map as Revealed by a Genome-Wide Gene Expression Analysis of Whole-Blood mRNA Transcriptome in Multiple Sclerosis

Background: Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls. Methodology/Principal Findings: We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value ,3.31E-6; V$CREBP1_Q2, p-value ,9.93E-6, V$YY1_02, p-value ,1.65E-5). Conclusions/Significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation

Conserved elements associated with ribosomal genes and their trans-splice acceptor sites in Caenorhabditis elegans

The recent publication of the Caenorhabditis elegans cisRED database has provided an extensive catalog of upstream elements that are conserved between nematode genomes. We have performed a secondary analysis to determine which subsequences of the cisRED motifs are found in multiple locations throughout the C. elegans genome. We used the word-counting motif discovery algorithm DME to form the motifs into groups based on sequence similarity. We then examined the genes associated with each motif group using DAVID and Ontologizer to determine which groups are associated with genes that also have significant functional associations in the Gene Ontology and other gene annotation sources. Of the 3265 motif groups formed, 612 (19%) had significant functional associations with respect to GO terms. Eight of the first 20 motif groups based on frequent dodecamers among the cisRED motif sequences were specifically associated with ribosomal protein genes; two of these were similar to mouse EBP-45, rat HNF3-family and Drosophila Zeste transcription factor binding sites. Additionally, seven motif groups were extensions of the canonical C. elegans trans-splice acceptor site. One motif group was tested for regulatory function in a series of green fluorescent protein expression experiments and was shown to be involved in pharyngeal expression

DNA Barcode Detects High Genetic Structure within Neotropical Bird Species

BACKGROUND: Towards lower latitudes the number of recognized species is not only higher, but also phylogeographic subdivision within species is more pronounced. Moreover, new genetically isolated populations are often described in recent phylogenies of Neotropical birds suggesting that the number of species in the region is underestimated. Previous COI barcoding of Argentinean bird species showed more complex patterns of regional divergence in the Neotropical than in the North American avifauna. METHODS AND FINDINGS: Here we analyzed 1,431 samples from 561 different species to extend the Neotropical bird barcode survey to lower latitudes, and detected even higher geographic structure within species than reported previously. About 93% (520) of the species were identified correctly from their DNA barcodes. The remaining 41 species were not monophyletic in their COI sequences because they shared barcode sequences with closely related species (N = 21) or contained very divergent clusters suggestive of putative new species embedded within the gene tree (N = 20). Deep intraspecific divergences overlapping with among-species differences were detected in 48 species, often with samples from large geographic areas and several including multiple subspecies. This strong population genetic structure often coincided with breaks between different ecoregions or areas of endemism. CONCLUSIONS: The taxonomic uncertainty associated with the high incidence of non-monophyletic species and discovery of putative species obscures studies of historical patterns of species diversification in the Neotropical region. We showed that COI barcodes are a valuable tool to indicate which taxa would benefit from more extensive taxonomic revisions with multilocus approaches. Moreover, our results support hypotheses that the megadiversity of birds in the region is associated with multiple geographic processes starting well before the Quaternary and extending to more recent geological periods

The Achievement of a Decentralized Water Management Through Stakeholder Participation: An Example from the Drôme River Catchment Area in France (1981–2008)

International audienceDifferent water Acts (e.g., the European Water Framework Directive) and stakeholders involved in aquatic affairs have promoted integrated river basin management (IRBM) over recent decades. However, few studies have provided feedback on these policies. The aim of the current article is to fill this gap by exploring how local newspapers reflect the implementation of a broad public participation within a catchment of France known for its innovation with regard to this domain. The media coverage of a water management strategy in the Drôme watershed from 1981 to 2008 was investigated using a content analysis and a geographic information system (GIS). We sought to determine what public participation and decentralized decision-making can be in practice. The results showed that this policy was integrated because of its social perspective, the high number of involved stakeholders, the willingness to handle water issues, and the local scale suitable for participation. We emphasized the prominence of the watershed scale guaranteed by the local water authority. This area was also characterized by compromise, arrangements, and power dynamics on a fine scale. We examined the most politically engaged writings regarding water management, which topics each group emphasized, and how the groups agreed and disagreed on issues based on their values and context. The temporal pattern of participation implementation was progressive but worked by fits and starts

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response