Cloning and characterisation of the human carbonic anhydrase I gene and mapping of the carbonic anhydrase gene cluster on chromosome 8

The carbonic anhydrase I gene (CA1) is part of a multigene family, the protein products of which are enzymes characterised by their ability to catalyse the reversible hydration of CO2. It exhibits a tissue specific pattern of expression, notably being expressed at high levels in erythroid cells in humans. It also shows regulation at a developmental level, with the CA1 protein at very low concentration in the blood of the foetus till a few weeks before birth. cDNA and genomic clones encoding CA1 were isolated and charachterised. Analysis of cDNA clones showed the presence of an occasional exon in the 5' leader of the transcript, while at the 3'-end two polyadenylation sites could be used, while analysis of genomic clones showed that CAI is atypical amongst the carbonic anhydrases in having a large intron of 36 kb separating the erythroid specific promoter from the coding region, making the entire gene some 50 kb in length. Pulsed-field gel electrophoresis was used in the analysis of the physical linkage relationship between CA1 and the CA2 and CA3 genes. Both of these genes lie 5' to CA1 and are transcribed away from it. CA3 lies centrally in this cluster separated from the 5' end of CA1 by 80 kb, while the 5'-end of CA2 lies some 20 kb downstream of the 3' end of CA3. The DNA methylation state of the gene in several erythroid and non-erythroid cell lines was examined. This showed that in the majority of these cell lines, which do not express the CA1 gene, extensive regions around CA1 were largely demethylated. In contrast, DNA from the only CA1 expressing cell line, HEL, appeared highly methylated at all HpaII sites tested apart for one site at the erythroid promoter and another at the 3'-end of the gene. High levels of methylation of the CA1 gene were also found in DNA from untransformed cells. The possible implications of this are discussed

Re-assessing Agrarian Policy and Practice in Local Environmental Management: The Case of Beef Cattle

There are policy pressures to make agriculture more environmentally sustainable and to give a more local expression to agri-environmental priorities. This paper considers these moves, with particular reference to the beef sector, and speculates on the further policy responses required to facilitate benign local agri-environmental management. The UK beef sector is characterized by its complexity and diversity but four major systems can be identified operating at varying levels of intensity. Of these, suckler herds and grass-rearing systems have long been associated with high natural value forms of agricultural land management. Many of the cherished habitats and landscapes of the UK are dependent upon grazing for their ecological and amenity value. However a combination of the BSE crisis, the strength of sterling and the recent Foot & Mouth epidemic threatens the sustainability of these high nature value grazing systems. The importance of grazing to fifty selected Sites of Special Scientific Interest is highlighted in the paper. Survey work identified a wide range of systems to be particularly vulnerable to changes in profitability in the beef sector, including: coastal grazing marsh, wet acidic grassland / marshland, upland moor and heath, calcareous grassland and neutral grassland. To maintain these systems requires agricultural policy to be more sensitive to local conditions than appears currently to be the case. There is little policy support for beef farmers in a regional context, still less giving special prominence to those farming within particular biotopes. Nor has there been sufficient policy encouragement to markets for traditional and local beef breeds. The continuing pressure for CAP reform offers further opportunity for policies to be devolved to regions and localities

Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy

Background Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. Methods Patients ( n  = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4 + T-cell counts had to be at or above the lower limit of normal. Results Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a ≥ 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses ( n  = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a ≥ 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. Conclusions Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65825/1/j.1365-4362.2003.01793.x.pd

Tracking infectious diseases in a warming world.

Using infectious diseases sensitive to climate as indicators of climate change helps stimulate andinform public health response

An alternative mode of epithelial polarity in the Drosophila midgut

Apical-basal polarity is essential for the formation and function of epithelial tissues, whereas loss of polarity is a hallmark of tumours. Studies in Drosophila have identified conserved polarity factors that define the apical (Crumbs, Stardust, Par-6, aPKC), junctional (Baz/Par-3) and basolateral (Scribbled, Discs large, Lgl) domains of epithelial cells1. Because these conserved factors mark equivalent domains in diverse vertebrate and invertebrate epithelial types, it is generally assumed that this system organises polarity in all epithelia. Here we show that this is not the case, as none of these canonical factors are required for the polarisation of the endodermal epithelium of the Drosophila adult midgut. Furthermore, unlike other Drosophila epithelia, the midgut forms occluding junctions above adherens junctions, as in vertebrates, and requires the integrin adhesion complex for polarity. Thus, Drosophila contains two types of epithelia that polarise by different mechanisms. Since knock-outs of canonical polarity factors often have little effect on the polarity of vertebrate epithelia, this diversity of polarity mechanisms is likely to be conserved in other animals

Interactive Sensory Objects Developed for and by People with Learning Disabilities

This paper describes a project that aims to help improve the accessibility of museums and heritage sites by creating a series of interactive, multisensory objects. The objects will be developed collaboratively by artists, technologists, people with an interest in heritage sites, and people with disabilities and their carers in a series of sensory art and electronics workshops. The workshops and the sensory objects will explore aspects of physicality and how to appeal to the entire range of senses for both control and feedback. In addition to creating new interactive objects, the project aims to learn more about how to engage people with disabilities as participant researchers in designing art objects, and how to make heritage sites more accessible generally

Developing H++ climate change scenarios for heat waves, droughts, floods, windstorms and cold snaps

This report describes the results of a project to investigate the development of plausible high-end climate change scenarios. It covers the following climate hazards: heat waves, cold snaps, low and high rainfall, droughts, floods and windstorms. The scope of the project does not extend into defining the consequences of these hazards such as mortality, property damage or impacts on the natural environment. The scenarios created for this report are referred to as H++ scenarios, and are typically more extreme climate change scenarios on the margins or outside of the 10th to 90th percentile range presented in the 2009 UK climate change projections (also known as ‘UKCP09’)

Agricultural Turns, Geographical Turns: Retrospect and Prospect.

It is accepted that British rural geography has actively engaged with the ‘cultural turn’, leading to a resurgence of research within the sub-discipline. However, a reading of recent reviews suggests that the cultural turn has largely, if not completely, bypassed those geographers interested in the agricultural sector. Farming centred engagements with notions of culture have been relatively limited compared with those concerned with the non-agricultural aspects of rural space. Indeed, agricultural geography represents something of an awkward case in the context of the disciplinary turn to culture, a situation that demands further exposition. In seeking explanation, it becomes evident that research on the farm sector is more culturally informed than initially appears. This paper argues that there have been both interesting and important engagements between agricultural geography and cultural perspectives over the past decade. The paper elaborates four specific areas of research which provide evidence for concern about the ‘culture’ within agriculture. The future contribution that culturally informed perspectives in geographical research can bring to agricultural issues is outlined by way of conclusion