PeerWise provides significant academic benefits to biological science students across diverse learning tasks, but with minimal instructor intervention.

We demonstrate that student engagement with PeerWise, an online tool that allows students to author and answer multiple-choice questions (MCQs), is associated with enhanced academic performance across diverse assessment types on a second year Genetics course. Benefits were consistent over three course deliveries, with differential benefits bestowed on groups of different prior ability. A rating scheme, to assess the educational quality of students' questions, is presented and demonstrates that our students are able intuitively to make such quality assessments, and that the process of authoring high quality questions alone does not explain the academic benefits. We further test the benefits of providing additional PeerWise support and conclude that PeerWise works efficiently with minimal intervention, and can be reliably assessed using automatically generated PeerWise scores.

Nucleosome positioning signals in the DNA sequence of the human and mouse H19 imprinting control regions.

We have investigated the sequences of the mouse and human H19 imprinting control regions (ICRs) to see whether they contain nucleosome positioning information pertinent to their function as a methylation-regulated chromatin boundary. Positioning signals were identified by an in vitro approach that employs reconstituted chromatin to comprehensively describe the contribution of the DNA to the most basic, underlying level of chromatin structure. Signals in the DNA sequence of both ICRs directed nucleosomes to flank and encompass the short conserved sequences that constitute the binding sites for the zinc finger protein CTCF, an essential mediator of insulator activity. The repeat structure of the human ICR presented a conserved array of strong positioning signals that would preferentially flank these CTCF binding sites with positioned nucleosomes, a chromatin structure that would tend to maintain their accessibility. Conversely, all four CTCF binding sites in the mouse sequence were located close to the centre of positioning signals that were stronger than those in their flanks; these binding sites might therefore be expected to be more readily incorporated into positioned nucleosomes. We found that CpG methylation did not effect widespread repositioning of nucleosomes on either ICR, indicating that allelic methylation patterns were unlikely to establish allele-specific chromatin structures for H19 by operating directly upon the underlying DNA-histone interactions; instead, epigenetic modulation of ICR chromatin structure is likely to be mediated principally at higher levels of control. DNA methylation did, however, both promote and inhibit nucleosome positioning at several sites in both ICRs and substantially negated one of the strongest nucleosome positioning signals in the human sequence, observations that underline the fact that this epigenetic modification can, nevertheless, directly and decisively modulate core histone-DNA interactions within the nucleosome.

Sequence analysis of transposable elements in the sea squirt, Ciona intestinalis.

A systematic search of 1 Mb of genomic sequences from the sea squirt, Ciona intestinalis, revealed the presence of six families of transposable elements. The Cigr-1 retrotransposon contains identical 245-bp long terminal repeats (LTRs) and a 3,630-bp open reading frame (ORF) encoding translation products in the same order as the domains characteristic of gypsy/Ty3-type LTR retrotransposons. The closest homologs of the reverse transcriptase domain were in gypsy elements from Drosophila and the sushi element from the pufferfish. However, the capsid-nucleocapsid region shows the clearest homology to an echinoderm element, Tgr1. Database searches also indicated two classes of non-LTR retrotransposon, named Cili-1 and Cili-2. The Cili-1 sequences show matches to regions of the ORF2 product of mammalian L1 elements. The Cili-2 sequences possess similarity to the RNaseH domain of Lian-Aa1, a mosquito non-LTR retrotransposon. The most abundant element was a short interspersed nucleotide element named Cics-1 with a copy number estimated at 40,000. Cics-1 consists of two conserved domains separated by an A-rich stretch. The 172-bp 5' domain is related to tRNA sequences, whereas the 110-bp 3' domain is unique. Cics-1 is unusual, not just in its modular structure, but also in its lack of a 3' poly(A) tail or direct flanking repeats. A second abundant element, Cimi-1, has an A+T-rich 193-bp consensus sequence and 30-bp terminal inverted repeats (TIRs) and is usually flanked by A+T-rich 2-4-bp putative target site duplications-characteristics of miniature inverted-repeat transposable elements found in plants and insects. A single 2,444-bp foldback element was found, possessing long TIRs containing an A+T-rich internal domain, an array of subrepeats, and a flanking domain at the TIR ends; this is the first example of a chordate foldback element. This study provides the first systematic characterization of the families of transposable elements in a lower chordate.

CpG island libraries from human chromosomes 18 and 22: landmarks for novel genes.

CpG islands are found at the 5' end of approximately 60% of human genes and so are important genomic landmarks. They are concentrated in early-replicating, highly acetylated gene-rich regions. With respect to CpG island content, human Chrs 18 and 22 are very different from each other: Chr 18 appears to be CpG island poor, whereas Chr 22 appears to be CpG island rich. We have constructed and validated CpG island libraries from flow-sorted Chrs 18 and 22 and used these to estimate the difference in number of CpG islands found on these two chromosomes. These libraries contain normalized collections of sequences from the 5' end of genes. Clones from the libraries were sequenced and compared with the sequence databases; one third matched ESTs, thus anchoring these ESTs at the 5' end of their gene. However, it was striking that many clones either had no match or matched only existing CpG island clones. This suggests that a significant proportion of 5' gene sequences are absent from databases, presumably either because they are difficult to clone or the gene is poorly expressed and/or has a restricted expression pattern. This point should be taken into consideration if the currently available libraries are those used for the elucidation of complete, as opposed to partial, gene sequences. The Chr 18 and 22 CpG island libraries are a sequence resource for the isolation of such 5' gene sequences from specific human chromosomes.

Nonmethylated transposable elements and methylated genes in a chordate genome.

The genome of the invertebrate chordate Ciona intestinalis was found to be a stable mosaic of methylated and nonmethylated domains. Multiple copies of an apparently active long terminal repeat retrotransposon and a long interspersed element are nonmethylated and a large fraction of abundant short interspersed elements are also methylation free. Genes, by contrast, are predominantly methylated. These data are incompatible with the genome defense model, which proposes that DNA methylation in animals is primarily targeted to endogenous transposable elements. Cytosine methylation in this urochordate may be preferentially directed to genes.

Gene number in an invertebrate chordate, Ciona intestinalis.

Gene number can be considered a pragmatic measure of biological complexity, but reliable data is scarce. Estimates for vertebrates are 50-100,000 genes per haploid genome, whereas invertebrate estimates fall below 25,000. We wished to test the hypothesis that the origin of vertebrates coincided with extensive gene creation. A prediction is that gene number will differ sharply between invertebrate and vertebrate members of the chordate phylum. A gene number estimation method requiring limited sequence sampling of genomic DNA was developed and validated by using data for Caenorhabditis elegans. Using the method, we estimated that the invertebrate chordate Ciona intestinalis has 15,500 protein-coding genes (+/-3,700). This number is significantly lower than gene numbers of vertebrate chordates, but similar to those of invertebrates in distantly related phyla. The data indicate that evolution of vertebrates was accompanied by a dramatic increase in protein-coding capacity of the genome.

Multidimensional Scaling of Binary Dissimilarities: Direct and Derived Approaches.

Given a matrix of dissimilarities, it has been debated whether researchers should perform multidimensional scaling on this original matrix or on a new one derived by comparing rows in the original matrix. Careful comparison studies (Drasgow & Jones, 1979; Van der Kloot & Van Herk, 1991) in the context of sorting data indicated that most of the initial enthusiasm for the derivative approach was unfounded. The current work, a Monte Carlo study of structured binary data derived from known two-dimensional configurations using ALSCAL, complements and extends the previous studies. We discuss a weakness in the squared difference (δ) row-comparison rule used previously and propose an alternative row-comparison measure based on the Jaccard coefficient. Scaling the binary data directly gave better performance, as gauged by Procrustes statistics, than did scaling A data across a range of noise levels. The quality of solutions obtained by scaling Jaccard data was always better or essentially equal to that from scaling δ data, and in certain parameter regions improved upon that of direct scaling. Another alternative approach, applying the δ rule after first row-centering the binary data, was found to be generally ineffective. These findings are pertinent to the analysis not just of stimulus sorting data but of coarse dissimilarities generally, for example from direct pairwise judgment tasks and in fields outside statistical psychology.

An evaluation of the use of multidimensional scaling for understanding brain connectivity.

A large amount of data is now available about the pattern of connections between brain regions. Computational methods are increasingly relevant for uncovering structure in such datasets. There has been recent interest in the use of non-metric multidimensional scaling (NMDS) for such analysis. NMDS produces a spatial representation of the 'dissimilarities' between a number of entities. Normally, it is applied to data matrices containing a large number of levels of dissimilarity, whereas for brain connectivity data there is a very small number. We address the suitability of NMDS for this case. Systematic numerical studies are presented to evaluate the ability of this method to reconstruct known geometrical configurations from dissimilarity data processing few levels. In this case there is a strong bias for NMDS to produce annular configurations, whether or not such structure exists in the original data. For the case of a connectivity dataset derived from the primate cortical visual system, we demonstrate that great caution is needed in interpreting the resulting configuration. Application of an independent method that we developed also strongly suggests that the visual system NMDS configuration is affected by an annular bias. We question the strength of support that an NMDS analysis of the visual system data provides for the two streams view of visual processing.