Holliday junction resolvase in Schizosaccharomyces pombe has identical endonuclease activity to the CCE1 homologue YDC2

A novel Holliday junction resolving activity has been identified in fractionated cell extracts of the fission yeast Schizosaccharomyces pombe . The enzyme catalyses endonucleolytic cleavage of Holliday junction-containing chi DNA and synthetic four-way DNA junctions. The activity cuts with high specificity a synthetic four-way junction containing a 12 bp core of homologous sequences but has no activity on another four-way junction (with a fixed crossover point), a three-way junction, linear duplex DNA or duplex DNA containing six mismatched nucleotides in the centre. The major cleavage sites map as single nicks in the vicinity of the crossover point, 3' of a thymidine residue. These data indicate that the activity has a strong DNA structure selectivity as well as a limited sequence preference; features similar to the Holliday junction resolving enzymes RuvC of Escherichia coli and the mitochondrial CCE1 (cruciform-cuttingenzyme 1) of Saccharomyces cerevisiae. A putative homologue of CCE1 in S.pombe (YDC2_SCHPO) has been identified through a search of the sequence database. The open reading frame of this gene has been cloned and the encoded protein, YDC2, expressed in E.coli . The purified recombinant YDC2 exhibits Holliday junction resolvase activity and is, therefore, a functional S.pombe homologue of CCE1. The resolvase YDC2 shows the same substrate specificity and produces identical cleavage sites as the activity obtained from S. pombe cells. Both YDC2 and the cellular activity cleave Holliday junctions in both orientations to give nicks that can be ligated in vitro. The partially purified Holliday junction resolving enzyme in fission yeast is biochemically indistinguishable from recombinant YDC2 and appears to be the same protein

Internal iamin structures within G1 nuclei of human dermal fibroblasts

The nuclear lamina is a mesh-like network of fibres subjacent to the inner nuclear membrane that is believed to be involved in the specific spatial reorganisation of chromatin after mitosis. To determine how the lamina might be involved in chromatin reorganisation, we have performed indirect immunofluorescence studies on quiescent and proliferating human dermal fibroblasts (HDF). Two monoclonal antibodies recognising human lamins A and C and three different fixation methods were employed. In indirect immunofluorescence studies, cultures of quiescent cells displayed a uniform perinuclear distribution of the antibodies. In proliferating cultures two distinct populations of cells were observed: one population displayed a typical perinuclear antibody distribution, while the second population displayed an unusual pattern consisting of a series of spots and fibres within the nucleus. By inducing cell-cycle synchrony in cultures we were able to determine that the unusual internal distribution of the lamin antibodies was restricted to cells in G1. Optical sectioning and 3-D reconstruction of the lamina structures in G1 nuclei was performed with a confocal laser scanning microscope (CLSM). This revealed that the internal lamin structures consisted of small foci and fibres proliferating throughout the nucleus. These structures were shown to be closely associated with areas of condensed chromatin but not nuclear membrane. As cells progress towards S phase the internal lamin foci disappear

Not just old and sick - the 'will to health' in later life

The end of the ‘Golden Age’ of welfare capitalism in the 1970s was the prelude to a period of greater individualisation within societies and was accompanied by an increase in the importance of consumption as a way of organising social relations. During the same period there was also an expansion in the discourses aimed at enhancing the government of the autonomous self. One such discourse operates around what has been termed the ‘will to health’: it suggests that health has become a required goal for individual behaviour and has become synonymous with health itself. The generational groups whose lifecourses were most exposed to these changes are now approaching later life. We explore the extent to which social transformations related to risk, consumption and individualisation are reflected in the construction of later-life identities around health and ageing. We examine how the growth in health-related ‘technologies of the self’ have fostered a distinction between natural and normal ageing, wherein the former is associated with coming to terms with physical decline and the latter associated with maintaining norms of self-care aimed at delaying such decline. Finally, we consider anti-ageing medicine as a developing arena for the construction of later-life identities and discuss the implications of the social changes for researching later life

Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities.

Background: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. Methods: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. Results: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. Conclusions: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. © 2013 Violante et al

National level promotion of physical activity: results from England's ACTIVE for LIFE campaign.

STUDY OBJECTIVE: To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity. DESIGN: three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants. SETTING: England. PARTICIPANTS: A nationally representative sample of 3189 adults aged 16-74 years. MAIN OUTCOME MEASURES: Awareness of the advertising element of the campaign, changes in knowledge of physical activity recommendations for health and self reported physical activity. RESULTS: 38% of participants were aware of the main advertising images, assessed six to eight months after the main television advertisement. The proportion of participants knowledgeable about moderate physical activity recommendations increased by 3.0% (95% CI: 1.4%, 4.5%) between waves 1 and 2 and 3.7% (95% CI: 2.1%, 5.3%) between waves 1 and 3. The change in proportion of active people between baseline and waves 1 and 2 was -0.02 (95% CI: -2.0 to +1.7) and between waves 1 and 3 was -9.8 (-7.9 to -11.7). CONCLUSION: The proportion of participants who were knowledgeable about the new recommendations, increased significantly after the campaign. There was however, no significant difference in knowledge by awareness of the main campaign advertisement. There is no evidence that ACTIVE for LIFE improved physical activity, either overall or in any subgroup

Further detections of OH masers in carbon stars with silicate features

A sample of J-type carbon stars was searched for OH maser emission. The new detection of three OH lines towards two silicate carbon stars is reported. In V778 Cyg, previously known as the main-lines (1665 and 1667 MHz) maser source, the satellite 1612 MHz emission was discovered while in NSV 2814 the main OH lines were detected. The presence of OH maser lines confirms the former suggestion that oxygen-rich material is located in the vicinity ($\approx$ $10^{15-16}$ cm) of silicate carbon stars.Comment: LaTeX2e, 4 pages with 2 figure

Proteoglycan neofunctions: regulation of inflammation and autophagy in cancer biology.

Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. We will critically discuss the dual role of proteoglycan-driven inflammation and autophagy in tumor biology, and delineate the potential mechanisms through which soluble extracellular matrix constituents affect the microenvironment associated with inflammatory and neoplastic diseases

HEAT TRANSFER IN A SINGLE VERTICAL TUBE CONDENSER-SUBCOOLER

A model for a vertical a condenser-subcooler is described. It is based upon tests performed with: - a monotubular pyrex condenser equipped for flow visualisation, - two metallic monotubular condensers-subcoolers (a steel one and a copper one) heavily equipped with measurement devices. Visualisation tests have shown that there is a sharp discontinuity between the condensation zone and the lower part of the tube. In this region (the flooded zone), the condensate completely fills the tube section. The limit between these two zones is stable in time and space. The model is built on the following assumptions: - the liquid film reaching the interface between the condensation and the flooded zones develops a hydrodynamical behaviour compared to a wall jet, - in the flooded zone, a mixed convection phenomenon occurs. Longitudinal temperature profiles measured along the tube axis are adequately described by selected correlations. Generally the new, simple model gives a better agreement than previous correlations, especially in the flooded zone; in some cases, the improvement for design reaches 100%