Interim 2001-based national population projections for the United Kingdom and constituent countries

This article describes new 2001-based national population projections which were carried out following the publication in September 2002 of the first results of the 2001 Census. These "interim" projections, carried out by the Government Actuary in consultation with the Registrars General, take preliminary account of the results of the Census which showed that the base population used in previous projections was overestimated. The interim projections also incorporate a reduced assumption of net international migration to the United Kingdom, informed by the first results of the 2001 Census and taking account of more recent migration information. The population of the United Kingdom is now projected to increase from an estimated 58.8 million in 2001 to reach 63.2 million by 2026. The projected population at 2026 is about 1.8 million (2.8 per cent) lower than in the previous (2000-based) projections.     

Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein

Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero.     

Stress response genes protect against lethal effects of sleep deprivation in Drosophila

Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep, and a circadian pacemaker that controls its timing. Although these two systems can operate independently, recent studies indicate a more intimate relationship. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01)). cyc(01) mutants showed a disproportionately large sleep rebound and died after 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants, cyc(01) flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc(01) flies from its lethal effects. Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation. These data represent the first step in identifying the molecular mechanisms that constitute the sleep homeostat.     

The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3

CD2 (known also as T11 (ref. 1), LFA-2 (ref. 2) and the erythrocyte rosette receptor (ref. 3] is a functionally important T lymphocyte surface glycoprotein of relative molecular mass 50,000 to 58,000 (Mr 50-58 K) which appears early in thymocyte ontogeny and is present on all mature T cells. Monoclonal antibodies to CD2 inhibit cytotoxic T-lymphocyte (CTL)-mediated killing by binding to the T lymphocyte and blocking adhesion to the target cell. Such antibodies also inhibit T helper cell responses including antigen-stimulated proliferation, interleukin-2 (IL-2) secretion, and IL-2 receptor expression. Certain combinations of monoclonal antibodies to CD2 epitopes trigger proliferation of peripheral blood T lymphocytes, cytotoxic effector function and expression of IL-2 receptors by thymocytes, resulting in thymocyte proliferation in the presence of exogenous IL-2 (ref. 11). These findings suggest that CD2 can function in signalling as well as being an adhesion molecule. To understand the role of CD2 in T-cell adhesion and activation, it is essential to define its natural ligand. Our previous observation that purified CD2 inhibits rosetting of T lymphocytes with sheep erythrocytes and can be absorbed by sheep erythrocytes suggested it also might bind with detectable affinity to human cells. We now report that CD2 binds to a cell-surface antigen known as lymphocyte function-associated antigen-3 (LFA-3) with high affinity, and can mediate adhesion of lymphoid cells via interaction with LFA-3.     

Antibiotic sensitivity testing by flow microcalorimetry

Summary The proposed flow microcalorimetric method for the diagnosis of bacteriuria has been extended to include antibiotic sensitivity testing. Sensitive organisms rapidly (4–8 min) show thermal responses to the added antibiotics over the normal range of concentrations (1×, 2×, MIC value).     

Interim 2003-based national population projections for the United Kingdom and constituent countries

The 2003-based national population projections, carried out by the Government Actuary in consultation with the Registrars General, and using essentially the same underlying assumptions as for the previous 2002-based projections, show the population of the United Kingdom rising from 59.6 million in 2003, passing 60 million during 2005, to reach 65.7 million by 2031. Longer-term projections suggest the population will peak around 2050 at nearly 67 million and then very gradually start to fall. The population will become older with the median age expected to rise from 38.4 years in 2003 to 43.3 years by 2031. In 2003, there were around 700 thousand (six per cent) more children aged under 16, than people of state pensionable age. However, from 2007, the population of pensionable age is projected to exceed the number of children.     

Was Feyerabend an anarchist? The structure(s) of ‘anything goes’

The near consensus in the secondary literature on Feyerabend is that his epistemological anarchism, characterized by the slogan ‘anything goes’, was not a positive proposal but the conclusion of a reductio argument against his opponents (Lloyd 1997; Staley 1999; Munévar 2000; Farrell 2003; Tsou 2003; Oberheim 2006; Roe 2009). This makes anarchism a mere criticism rather than a substantive position in its own right. In this paper, I argue that Feyerabend held anarchism as a positive thesis. Specifically, I present two possible interpretations of anarchism: one where anarchism is entailed by Feyerabend's radical view of pluralism and another where scientists must be ‘methodological opportunists’, which Feyerabend held simultaneously from at least 1970. I then consider how these positions fare against the more influential criticisms of anarchism (Nagel 1977; Worrall 1978; Godfrey-Smith 2003). I conclude by suggesting two avenues to constraining a literal interpretation of ‘anything goes’ on Feyerabendian grounds.     

Summer habitat use by Columbian Sharp-tailed Grouse in western Idaho

We studied summer habitat use by Columbian Sharp-tailed Grouse ( Tympanuchus phasianellus columbianus ) in western Idaho during 1983-85. Vegetative and topographic measurements were recorded at 716 locations of 15 radio-tagged grouse and at 180 random sites within the major vegetation/cover types in the study area. The mean size of summer home ranges was 1.87 ± 1.14 km 2 . Of eight cover types identified in the study area, individual grouse used the big sagebrush Artemisia tridentata ) cover type more than or in proportion to availability, the low sagebrush ( A. arbuscula ) in proportion to availability, and avoided the shrubby eriogonum ( Eriogonum spp.) type. Characteristics of the big sagebrush cover type that Sharp-tailed Grouse preferred include moderate vegetative cover, high plant species diversity, and high structural diversity. Grouse used areas of dense cover (i.e., mountain shrub and riparian cover types) primarily for escape cover. Compared with random sites, grouse selected areas with (1) greater horizontal and vertical cover, (2) greater canopy coverage of forbs typically decreased by livestock grazing, (3) greater density and canopy coverage of arrowleaf balsamroot ( Balsamorhiza sagittata ), and (4) greater canopy coverage of bluebunch wheatgrass ( Agropyron spicatum ) in the big sagebrush cover type in 1984 and the low sagebrush cover type in 1985. The importance of the native perennials arrowleaf balsamroot and bluebunch wheatgrass became apparent during a drought year when many exotic annuals dried up and provided no cover. Overall, grouse selected vegetative communities that were least modified by livestock grazing.     

Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome

Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders.