The pathophysiology of HOX genes and their role in cancer

The HOM-C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho-physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co-ordinated during development, so that the 3' genes are expressed more anteriorly and earlier than the 5' genes. Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand-foot-genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly. Haematopoietic progenitors express HOX genes in a pattern characteristic of the lineage and stage of differentiation of the cells. In leukaemia, dysregulated HOX gene expression can occur due to chromosomal translocations involving upstream regulators such as the MLL gene, or the fusion of a HOX gene to another gene such as the nucleoporin, NUP98. Recent investigations of HOX gene expression in leukaemia are providing important insights into disease classification and prediction of clinical outcome. Whereas the oncogenic potential of certain HOX genes in leukaemia has already been defined, their role in other neoplasms is currently being studied. Progress has been hampered by the experimental approach used in many studies in which the expression of small subsets of HOX genes was analysed, and complicated by the functional redundancy implicit in the HOX gene system. Attempts to elucidate the function of HOX genes in malignant transformation will be enhanced by a better understanding of their upstream regulators and downstream target genes.

The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.

T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.

Under-water scene investigation using ground penetrating radar (GPR) in the search for a sunken jet ski, Northern Ireland

A search for a submerged jet ski and the lost limb of its driver involved in a collision with a speedboat was made in a shallow lake in Northern Ireland. The location of both was crucial to establishing events at the time of the accident. Local intelligence suggested both objects were likely to be partially-buried by lacustrine silt. To avoid sediment churning, this required non-invasive, completely non-destructive assessment and mapping of the scene. A MALA RAMAC ground-penetrating radar system (GPR) mounted on floats for surveying from walkways and jetties or placed in a small rubber dinghy for offshore profiling was used. A grid was established and each line surveyed with 100, 200 and 400MHz antennae. In waters over 6m deep GPR data showed the form of the lake floor but excessive ringing occurred in the data. In waters less than 6m deep ringing diminished on both 100 and 200MHz data, the latter displaying the best trade-off between depth penetration and horizontal object resolution. 400MHz data failed to be of use in waters over 2m deep and at these depths showed only limited improvement of image quality compared to 200MHz data. Surface objects such as a wooden walkway caused interference on 200 and 400MHz data when antennae were oriented both normal and parallel to survey direction; this may be a function of the low attenuation of radar waves in freshwater, allowing excellent lateral and vertical radar wave penetration. On 200MHz data the damaged jet-ski was clearly imaged in a location that contradicted the speedboat driver's account of the accident.

'Ulster's policing goes global': The police reform process in Northern Ireland and the creation of a global brand

This paper engages with contemporary discussions in relation to the commodification of policing and security. It suggests that the existing literature regarding these trends has been geared primarily towards commercial security providers and has failed to address the processes by which public policing models are commodified and marketed both within, and through, the transnational policing community. Drawing upon evidence from the police change process in Northern Ireland, we argue that a Northern Irish Policing Model (NIPM) has emerged in the aftermath of the Independent Commission on Policing (ICP) reforms. This is increasingly branded and promoted on the global stage. Furthermore, we suggest that the NIPM is not monolithic, but segmented, and targeted towards a number of different 'consumers' both domestically and transnationally. Reflecting these diverse markets, the NIPM draws upon two seemingly incongruous constituent elements: the 'best practice' lessons of policing transition, as embodied in the ICP reforms; and, the legacy of counter-terrorism expertise drawn from the preceding decades of conflict. The discussion concludes by querying as to which of these components of the NIPM is in the ascendancy.

Persistent measles virus infection of mouse neural cells lacking known human entry receptors

Aims: Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry.

Methods: To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction.

Results: WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections.

Conclusions: WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections.

Remote Detection and Identification of Organic Remains: An Assessment of Archaeological Potential

This paper reviews the various methods of using natural or induced light spectra as analytical tools in forensic archaeology. Chemical identi?cation can be made at long range and wide scale (tens of metres) down to short range and very small scale (nanometres). The identi?cation of organic gases and materials has used either chemical capture and chromatography, induced (laser or ultraviolet) light sources or laser Raman microscope spectroscopy. The remote gas detection method relies on the identi?cation of atmospheric gases by their characteristic light spectra. Modern spectroscopes can detect gases down to a few parts per million of an atmosphere. When the light source (wavelength) and direction is controlled, so laser-induced spectroscopy may be used to monitor the emission of gases such methane from buried organic remains. In order to identify the location of buried organic remains, a grid of sample points must be established using a base line or global
positioning system. When matched to base line or ground-positioning systems, such data can be manipulated by geographical information system packages. This would enable pinpointing of anomalies for excavation or avoidance. Microscope-based laser Raman spectroscopy can be used to directly analyse captured gases, swabs and surfaces without the problems of long-path detection. Copyright ? 2002 John Wiley & Sons, Ltd.