14-3-3SIGMA NEGATIVELY REGULATES THE STABILITY AND SUBCELLULAR LOCALIZATION OF COP1

Mammalian constitutive photomorphogenic 1 (COP1), a p53 E3 ubiquitin ligase, is a key negative regulator for p53. DNA damage leads to the translocation of COP1 to the cytoplasm, but the underlying mechanism remains unknown. We discovered that 14-3-3σ controlled COP1 subcellular localization and protein stability. Investigation of the underlying mechanism suggested that, upon DNA damage, 14-3-3σ bound to phosphorylated COP1 at S387, resulting in COP1 translocation to the cytoplasm and cytoplasmic COP1 ubiquitination and proteasomal degradation. 14-3-3σ targeted COP1 for degradation to prevent COP1-mediated p53 degradation, p53 ubiquitination, and p53 transcription repression. COP1 expression promoted cell proliferation, cell transformation, and tumor progression, attesting to its role in cancer promotion. 14-3-3σ negatively regulated COP1 function and prevented tumor growth in cancer xenografts. COP1 protein levels were inversely correlated with 14-3-3σ protein levels in human breast and pancreatic cancer specimens. Together, these results define a novel, detailed mechanism for the posttranslational regulation of COP1 upon DNA damage and provide a mechanistic explanation of the correlation of COP1 overexpression with 14-3-3σ downregulation during tumorigenesis.

Intensive Family Preservation in Children's Mental Health: Predictors of Placement

This article examines the predictors of placement following IFPSfor a sample of child mental health service recipients and their families. Risk and protective factors vary depending on the time frame under consideration. Immediately following service, children 's level of Social/Legal functioning, a previous group home placement, and the presence of mental health problems for other family members increase risk of placement, while the number of follow-up services serves to lessen risk. Three to six months after service, the presence of a child behavior presenting problem and a projected placement in foster care serve as protective factors, while two service targets, alcohol monitoring and time management, serve to increase risk. Appropriate use of results for program design and for structuring access to services is discussed.

What is ‘wood’ – An anatomical re-definition

The technical definition of ‘wood’ is well accepted, but its botanical understanding remains vague. Different degrees and amounts of lignification in plants and their imprecise description, together with a conceptually doubtful life form catalog including trees, shrubs and herbs further complicate our understanding of ‘wood’. Here, we use permanent micro sections to demonstrate that the xylem and bark of terrestrial plants can vary from one tissue with a few lignified cells to an almost fully lignified tissue. This universal principle of plant growth and stabilization, accounting for all taxonomic units within vascular plants, suggests that the classical life form separation into herbs, shrubs and trees is not valid. An anatomical-based differentiation between ‘wood’, ‘woody’ and ‘woodiness’ is also only meaningful if supplemented by insight on the particular plant section and its lignified proportion. We therefore recommend utilizing the botanically more neutral term ‘stem anatomy’ instead of ‘wood anatomy’, which further implies integration of the xylem and bark of all terrestrial plants. Since dendrochronology considers shrubs, dwarf shrubs and perennial herbs in addition to trees, its semantic expansion toward ‘xylemchronology’ might be worthwhile considering.

Visual disturbance following sclerotherapy for varicose veins, reticular veins and telangiectasias: a systematic literature review.

The objective of the study was to review the literature reporting visual disturbance (VD)following sclerotherapy for varicose veins. Underlying mechanisms will be discussed. A literature search of the databases Medline and Google Scholar was performed. Original articles including randomized trials, case series and case reports reporting VD in humans following sclerotherapy for varicose veins were included. Additional references were also obtained if they had been referenced in related publications. The search yielded 4948 results of which 25 reports were found to meet the inclusion criteria. In larger series with at least 500 included patients the prevalence of VD following sclerotherapy ranges from 0.09% to 2%. In most reports foam sclerotherapy was associated with VD (19); exclusive use of liquid sclerosant was reported in two cases, some reports included foam and liquid sclerosant (4). There were no persistent visual disorders reported. VD occurred with polidocanol and sodium tetradecyl sulphate in different concentrations (0.25–3%). Various forms of foam preparation including various ways of foam production and the liquid –air ratio (1 or 2 parts of liquid mixed with 3, 4 or 5 parts of air) were reported in association with the occurrence of VD. VDs following sclerotherapy for varicose veins are rare and all reported events were transient. Bubble embolism or any kind of embolism seems unlikely to be the only underlying mechanism. A systemic inflammatory response following sclerotherapy has been suggested. Further research to clarify the mechanism of action of sclerosants is required.

Antarctic Volcanic Flux Ratios from Law Dome Ice Cores

Explosive volcanic eruptions can inject large quantities of sulphur dioxide into the stratosphere. The aerosols that result from oxidation of the sulphur dioxide can produce significant cooling of the troposphere by reflecting or absorbing solar radiation. It is possible to obtain an estimate of the relative stratospheric sulphur aerosol concentration produced by different volcanoes by comparing sulphuric acid fluxes determined by analysis of polar ice cores. Here, we use a non-sea-salt sulphate time series derived from three well-dated Law Dome ice cores to investigate sulphuric acid flux ratios for major eruptions over the period AD 1301-1995. We use additional data from other cores to investigate systematic spatial variability in the ratios. Only for the Kuwae eruption (Law Dome ice date AD 1459.5) was the H2SO4 flux larger than that deposited by Tambora (Law Dome ice date AD 1816.7).

Species Assemblages of Leptocephali in the Southwestern Sargasso Sea

Catches of leptocephali of shelf and slope marine eels of the Chlopsidae, Congridae, Moringuidae, Muraenidae, and Ophichthidae collected during a survey in the southwestern Sargasso Sea in late September and early October 1984 were analyzed to learn about their reproductive ecology and larval transport. Sampling along a transect from the Florida Current (FC) out across the southwestern Sargasso Sea and in the Northwest Providence Channel (NWPC) of the Northern Bahamas enabled the evaluation of the larval distributions, abundances and size ranges, regional assemblage structure, and the apparent spawning areas of these marine eels. Distinctly different assemblages observed in the FC and NWPC included the congrid genera Heteroconger, Paraconger, Uroconger, and many ophichthid species, which were rare or absent offshore. Other taxa of congrids, chlopsids, muraenids and moringuids were present in all areas, but the smallest specimens of most taxa were only caught at the NWPC or FC stations. Multivariate analyses reflected higher richness and abundance in the FC and NWPC and also similar species compositions in offshore areas. The patterns of distribution of these leptocephali differed from those of anguillid, nettastomatid, and mesopelagic eel leptocephali collected in the same survey. These findings support the hypothesis that most taxa of marine eels spawn close to their adult habitats, and indicate that despite high biodiversity of marine eels in the Northern Bahamas, only some species of leptocephali appear to get transported far offshore by ocean currents.

What does your neighbourhood say about you? A study of life expectancy in 1.3 million Swiss neighbourhoods

BACKGROUND Switzerland had the highest life expectancy at 82.8 years among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Geographical variation of life expectancy and its relation to the socioeconomic position of neighbourhoods are, however, not well understood. METHODS We analysed the Swiss National Cohort, which linked the 2000 census with mortality records 2000-2008 to estimate life expectancy across neighbourhoods. A neighbourhood index of socioeconomic position (SEP) based on the median rent, education and occupation of household heads and crowding was calculated for 1.3 million overlapping neighbourhoods of 50 households. We used skew-normal regression models, including the index and additionally marital status, education, nationality, religion and occupation to calculate crude and adjusted estimates of life expectancy at age 30 years. RESULTS Based on over 4.5 million individuals and over 400 000 deaths, estimates of life expectancy at age 30 in neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years in women. The correlation between life expectancy and neighbourhood SEP was strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison of the lowest with the highest percentile of neighbourhood SEP, the crude difference in life expectancy from skew-normal regression was 4.5 years in men and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9 years, respectively (all p values <0.0001). CONCLUSIONS Although life expectancy is high in Switzerland, there is substantial geographical variation and life expectancy is strongly associated with the social standing of neighbourhoods.