The alpha-effect in cyclic secondary amines: new scaffolds for iminium ion accelerated transformations

Five-membered secondary amine heterocycles containing an α-heteroatom were prepared and shown to be ineffective as catalysts for the iminium ion catalysed Diels–Alder reaction between cinnamaldehyde and cyclopentadiene. Their six-membered counterparts proved to be highly active catalysts. In stark contrast, the catalytic activity observed when comparing the non α-heteroatom cyclic amines proline methyl ester and methyl pipecolinate showed the five-membered ring amine was significantly more active. Concurrent density functional theoretical calculations suggest a rationale for the observed trends in reactivity, highlighting that LUMO activation through an iminium ion intermediate plays a key role in catalytic activity

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution

Insensitivity of alkenone carbon isotopes to atmospheric CO₂ at low to moderate CO₂ levels

Atmospheric pCO2 is a critical component of the global carbon system and is considered to be the major control of Earth’s past, present and future climate. Accurate and precise reconstructions of its concentration through geological time are, therefore, crucial to our understanding of the Earth system. Ice core records document pCO2 for the past 800 kyrs, but at no point during this interval were CO2 levels higher than today. Interpretation of older pCO2 has been hampered by discrepancies during some time intervals between two of the main ocean-based proxy methods used to reconstruct pCO2: the carbon isotope fractionation that occurs during photosynthesis as recorded by haptophyte biomarkers (alkenones) and the boron isotope composition (δ11B) of foraminifer shells. Here we present alkenone and δ11B-based pCO2 reconstructions generated from the same samples from the Plio-Pleistocene at ODP Site 999 across a glacial-interglacial cycle. We find a muted response to pCO2 in the alkenone record compared to contemporaneous ice core and δ11B records, suggesting caution in the interpretation of alkenone-based records at low pCO2 levels. This is possibly caused by the physiology of CO2 uptake in the haptophytes. Our new understanding resolves some of the inconsistencies between the proxies and highlights that caution may be required when interpreting alkenone-based reconstructions of pCO2

Do echinoderm genomes measure up?

Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org

Gene structure in the sea urchin Strongylocentrotus purpuratus based on transcriptome analysis

A comprehensive transcriptome analysis has been performed on protein-coding RNAs of Strongylocentrotus purpuratus, including 10 different embryonic stages, six feeding larval and metamorphosed juvenile stages, and six adult tissues. In this study, we pooled the transcriptomes from all of these sources and focused on the insights they provide for gene structure in the genome of this recently sequenced model system. The genome had initially been annotated by use of computational gene model prediction algorithms. A large fraction of these predicted genes were recovered in the transcriptome when the reads were mapped to the genome and appropriately filtered and analyzed. However, in a manually curated subset, we discovered that more than half the computational gene model predictions were imperfect, containing errors such as missing exons, prediction of nonexistent exons, erroneous intron/exon boundaries, fusion of adjacent genes, and prediction of multiple genes from single genes. The transcriptome data have been used to provide a systematic upgrade of the gene model predictions throughout the genome, very greatly improving the research usability of the genomic sequence. We have constructed new public databases that incorporate information from the transcriptome analyses. The transcript-based gene model data were used to define average structural parameters for S. purpuratus protein-coding genes. In addition, we constructed a custom sea urchin gene ontology, and assigned about 7000 different annotated transcripts to 24 functional classes. Strong correlations became evident between given functional ontology classes and structural properties, including gene size, exon number, and exon and intron size

The cloning, genomic organization and tissue expression profile of the human DLG5 gene

BACKGROUND: Familial atrial fibrillation, an autosomal dominant disease, was previously mapped to chromosome 10q22. One of the genes mapped to the 10q22 region is DLG5, a member of the MAGUKs (Membrane Associated Gyanylate Kinase) family which mediates intracellular signaling. Only a partial cDNA was available for DLG5. To exclude potential disease inducing mutations, it was necessary to obtain a complete cDNA and genomic sequence of the gene. METHODS: The Northern Blot analysis performed using 3' UTR of this gene indicated the transcript size to be about 7.2 KB. Using race technique and library screening the entire cDNA was cloned. This gene was evaluated by sequencing the coding region and splice functions in normal and affected family members with familial atrial fibrillation. Furthermore, haploid cell lines from affected patients were generated and analyzed for deletions that may have been missed by PCR. RESULTS: We identified two distinct alternately spliced transcripts of this gene. The genomic sequence of the DLG5 gene spanned 79 KB with 32 exons and was shown to have ubiquitous human tissue expression including placenta, heart, skeletal muscle, liver and pancreas. CONCLUSIONS: The entire cDNA of DLG5 was identified, sequenced and its genomic organization determined

Analysis of Human Immunodeficiency Virus Type 1 Integrase Mutants

AbstractThe human immunodeficiency virus type-1 (HIV-1) integrase protein (IN) mediates the insertion of linear double-stranded viral DNA into the host genome. Mutations in IN can have different effects on the virus life cycle. In this study, Gag-Pol polyprotein processing, Tat synthesis, and vital replication were investigated in integrase-defective HIV-1 mutants. In the absence of IN synthesis, the Gag-Pol polyprotein stability, packaging, and/or processing was reduced. There was limited expression of Tat observed in IN mutants, but no viral replication

What do students want most from written feedback information? Distinguishing necessities from luxuries using a budgeting methodology

Feedback is a key concern for higher education practitioners, yet there is little evidence concerning the aspects of assessment feedback information that higher education students prioritise when their lecturers’ time and resources are stretched. One recent study found that in such circumstances, students actually perceive feedback information itself as a luxury rather than a necessity. We first re-examined that finding by asking undergraduates to ‘purchase’ characteristics to create the ideal lecturer, using budgets of differing sizes to distinguish necessities from luxuries. Contrary to the earlier research, students in fact considered good feedback information the single biggest necessity for lecturers to demonstrate. In a second study we used the same method to examine the characteristics of feedback information that students value most. Here, the most important perceived necessity was guidance on improvement of skills. In both studies, students’ priorities were influenced by their individual approaches to learning. These findings permit a more pragmatic approach to building student satisfaction in spite of growing expectations and demands