Conservation of long-range synteny and microsynteny between the genomes of two distantly related nematodes

BACKGROUND: Comparisons between the genomes of the closely related nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal high rates of rearrangement, with a bias towards within-chromosome events. To assess whether this pattern is true of nematodes in general, we have used genome sequence to compare two nematode species that last shared a common ancestor approximately 300 million years ago: the model C. elegans and the filarial parasite Brugia malayi. RESULTS: An 83 kb region flanking the gene for Bm-mif-1 (macrophage migration inhibitory factor, a B. malayi homolog of a human cytokine) was sequenced. When compared to the complete genome of C. elegans, evidence for conservation of long-range synteny and microsynteny was found. Potential C. elegans orthologs for II of the 12 protein-coding genes predicted in the B. malayi sequence were identified. Ten of these orthologs were located on chromosome I, with eight clustered in a 2.3 Mb region. While several, relatively local, intrachromosomal rearrangements have occurred, the order, composition, and configuration of two gene clusters, each containing three genes, was conserved. Comparison of B. malayi BAC-end genome survey sequence to C. elegans also revealed a bias towards intrachromosome rearrangements. CONCLUSIONS: We suggest that intrachromosomal rearrangement is a major force driving chromosomal organization in nematodes, but is constrained by the interdigitation of functional elements of neighboring genes

Computer memories: the history of computer form

This paper looks at the computer as a truly global form. The similar beige boxes found in offices across the world are analysed from the perspective of design history rather than that of the history of science and technology. Through the exploration of an archive of computer manufacturer's catalogues and concurrent design texts, this paper examines the changes that have occurred in the production and consumption of the computer in the context of the workplace, from its inception as a room-sized mainframe operated through a console of flashing lights, to the personal computer as a 'universal' form, reproduced by many manufacturers. It shows how the computer in the past has been as diverse as any other product, and asks how and why it now appears as a standardised, sanitised object. In doing so our relationship with the office computer, past and present is explored, revealing a complex history of vicissitude.</p

Vaccination with novel low-molecular weight proteins secreted from Trichinella spiralis inhibits establishment of infection

Trichinella spiralis muscle stage larvae (mL1) produce excretory-secreted products (ESPs), a complex mixture of protein, which are believed to be important for establishing or maintaining an infection niche within skeletal muscle and the intestine. Studies of both whole ESPs and individual cloned proteins have shown that some ESPs are potent immunogens capable of eliciting protective immune responses. Here we describe two novel proteins, Secreted from Muscle stage Larvae SML-4 and SML-5 which are 15 kDa and 12 kDa respectively. The genes encoding these proteins are highly conserved within the Trichinellids, are constituents of mL1 ESP and localized in the parasite stichosome. While SML-5 is only expressed in mL1 and early stages of adult nematode development, SML-4 is a tyvosylated glycoprotein also produced by adult nematodes, indicating it may have a function in the enteral phase of the infection. Vaccination with these proteins resulted in an impaired establishment of adult stages and consequently a reduction in the burden of mL1 in BALB/c mice. This suggests that both proteins may be important for establishment of parasite infection of the intestine and are prophylactic vaccine candidates

A molecular map of mesenchymal tumors

Background Bone and soft tissue tumors represent a diverse group of neoplasms thought to derive from cells of the mesenchyme or neural crest. Histological diagnosis is challenging due to the poor or heterogenous differentiation of many tumors, resulting in uncertainty over prognosis and appropriate therapy. Results We have undertaken a broad and comprehensive study of the gene expression profile of 96 tumors with representatives of all mesenchymal tissues, including several problem diagnostic groups. Using machine learning methods adapted to this problem we identify molecular fingerprints for most tumors, which are pathognomonic (decisive) and biologically revealing. Conclusion We demonstrate the utility of gene expression profiles and machine learning for a complex clinical problem, and identify putative origins for certain mesenchymal tumor

Kondo effect in systems with dynamical symmetries

This paper is devoted to a systematic exposure of the Kondo physics in quantum dots for which the low energy spin excitations consist of a few different spin multiplets $|S_{i}M_{i}>$. Under certain conditions (to be explained below) some of the lowest energy levels $E_{S_{i}}$ are nearly degenerate. The dot in its ground state cannot then be regarded as a simple quantum top in the sense that beside its spin operator other dot (vector) operators ${\bf R}_{n}$ are needed (in order to fully determine its quantum states), which have non-zero matrix elements between states of different spin multiplets $\ne 0$. These "Runge-Lenz" operators do not appear in the isolated dot-Hamiltonian (so in some sense they are "hidden"). Yet, they are exposed when tunneling between dot and leads is switched on. The effective spin Hamiltonian which couples the metallic electron spin ${\bf s}$ with the operators of the dot then contains new exchange terms, $J_{n} {\bf s} \cdot {\bf R}_{n}$ beside the ubiquitous ones $J_{i} {\bf s}\cdot {\bf S}_{i}$. The operators ${\bf S}_{i}$ and ${\bf R}_{n}$ generate a dynamical group (usually SO(n)). Remarkably, the value of $n$ can be controlled by gate voltages, indicating that abstract concepts such as dynamical symmetry groups are experimentally realizable. Moreover, when an external magnetic field is applied then, under favorable circumstances, the exchange interaction involves solely the Runge-Lenz operators ${\bf R}_{n}$ and the corresponding dynamical symmetry group is SU(n). For example, the celebrated group SU(3) is realized in triple quantum dot with four electrons.Comment: 24 two-column page

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

$\textit{Rationale}$ Impairments in behavioral flexibility lie at the core of anxiety and obsessive-compulsive disorders. Few studies, however, have investigated the neural substrates of natural variation in behavioral flexibility and whether inflexible behavior is linked to anxiety and peripheral markers of stress and monoamine function. $\textit{Objective}$ The objective of the study was to investigate peripheral and central markers associated with perseverative behavior on a spatial-discrimination serial reversal learning task. $\textit{Methods}$ Rats were trained on a reversal learning task prior to blood sampling, anxiety assessment, and the behavioral evaluation of selective monoamine oxidase-A (MAO-A) and MAO-B inhibitors, which block the degradation of serotonin (5-HT), dopamine (DA), and noradrenaline (NA). $\textit{Results}$ Perseveration correlated positively with 5-HT levels in blood plasma and inversely with trait anxiety, as measured on the elevated plus maze. No significant relationships were found between perseveration and the stress hormone corticosterone or the 5-HT precursor tryptophan. Reversal learning was significantly improved by systemic administration of the MAO-A inhibitor moclobemide but not by the MAO-B inhibitor lazabemide. Moclobemide also increased latencies to initiate a new trial following an incorrect response suggesting a possible role in modulating behavioral inhibition to negative feedback. MAO-A but not MAO-B inhibition resulted in pronounced increases in 5-HT and NA content in the orbitofrontal cortex and dorsal raphé nuclei and increased 5-HT and DA content in the basolateral amygdala and dorsomedial striatum. $\textit{Conclusions}$ These findings indicate that central and peripheral monoaminergic mechanisms underlie inter-individual variation in behavioral flexibility, which overlaps with trait anxiety and depends on functional MAO-A activity.This work was supported by Medical Research Council Grants (G0701500, G9536855), a Wellcome Trust Senior Investigator Award to TW Robbins (106431/Z/14/Z).and by a Core Award from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10/Z) to the Behavioural and Clinical Neuroscience Institute. PZ was supported by the Pinsent Darwin studentship from the Physiology, Development, and Neuroscience Department. JA was supported by a Fellowship from the Swedish Research Council. BJ was supported by Fellowships from the AXA Research Fund, the National Health and Medical Research Council of Australia, and the Cambridge Newton Trust