Multiple Molecular Mechanisms Underlying Subdiagnostic Variants of Marfan Syndrome

Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.     

Analysis of mannose selection used for transformation of sugar beet

Various factors affecting mannose selection for the production of transgenic plants were studied using Agrobacterium tumefaciens-mediated transformation of sugar beet (Beta vulgaris L.) cotyledonary explants. The selection system is based on the Escherichia coli phosphomannose isomerase (PMI) gene as selectable gene and mannose as selective agent. Transformation frequencies were about 10-fold higher than for kanamycin selection but were only obtained at low selection pressures (1.0–1.5 g/l mannose) where 20–30% of the explants produced shoots. The non-transgenic shoots were eliminated during the selection procedure by a stepwise increase in the mannose concentration up to 10 g/l. Analysis of the transformed shoots showed that the PMI activity varied from 2.4 mU/mg to 350 mU/mg but the expression level was independent of the selection pressure. Complete resistance to mannose of transformed shoots was observed already at low PMI activities (7.5 mU/mg). Genomic DNA blot analysis confirmed the presence of the PMI gene in all transformants analysed. The possible mode of action of mannose selection compared to other selection methods is discussed.     

Concanavalin A binding and endoglycosidase D resistance of beta1,2-xylosylated and alpha 1,3-fucosylated plant and insect oligosaccharides

The binding to concanavalin A (Con A) by pyridylaminated oligosaccharides derived from bromelain (Man alpha 1,6(Xyl beta 1, 2) Man beta 1, 4GlcNAc beta 1, 4(Fuc alpha 1, 3)GlcNAc), horseradish peroxidase (Man alpha 1,6(Man alpha 1, 3) (Xyl beta 1, 2)Man beta 1, 4GlcNAc beta 1,4(Fuc alpha 1, 3) GlcNAc), bee venom phospholipase A2 (Man alpha 1,6Man beta 1,4GlcNAc beta 1,4GlcNAc and Man alpha 1,6(Man alpha 1, 3)Man beta 1,4GlcNAc beta 1, 4 (Fuc alpha 1, 3)GlcNAc) and zucchini ascorbate oxidase (Man alpha 1,6(Man alpha 1, 3) (Xyl beta 1, 2)Man beta 1, 4 GlcNAc beta 1, 4GlcNAc) was compared to the binding by Man3GlcNAc2, Man5GlcNAc2 and the asialo-triantennary complex oligosaccharide from bovine fetuin. While the fetuin oligosaccharide did not bind, bromelain, zucchini, Man2GlcNAc2 and horseradish peroxidase were retarded (in that order). The alpha 1, 3-fucosylated phospholipase, Man3GlcNAc2 and Man5GlcNAc2 structures were eluted with 15 M alpha -methylmannoside. It is concluded that core alpha 1,3-fucosylation has little or no effect on ConA binding while xylosylation decreases affinity for ConA. In a parallel study comparing the endoglycosidase D (Endo D) sensitivities of Man3GlcNAc2, IgG-derived GlcNAc beta 1, 2Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1,4GlcNAc beta 1,4(Fuc alpha 1,6)GlcNAc, the phospholipase Man alpha 1,6(Man alpha 1, 3)Man beta 1, 4GlcNAc beta 1,4(Fuc alpha 1,3)GlcNAc, and horseradish and zucchini pyridylaminated N-linked oligosaccharides, it was found that only the Man3GlcNAc2 structure was cleaved. The IgG structure was sensitive only when beta -hexosaminidase was also present. Thus, in contrast to core alpha 1,6-fucosylated structures, such as those present in mammals, the presence of core alpha 1,3-fucose, as found in structures from plants and insects, and/or beta 1,2-xylose, as found in plants, causes resistance to Endo D.     

Analysis of the potential for survival and seasonal activity of Aedes albopictus (Diptera: Culicidae) in the United Kingdom.

The international trade in used tires, coupled with the ability to lay non-desiccating eggs, has enabled Aedes albopictus (Skuse) (Diptera: Culicidae) to travel and establish on new continents, including North, Central, and South America, the Caribbean, Australasia, Africa, and Europe. Concerns have been raised over its potential role in the transmission of arboviruses and Dirofilaria nematodes. Following importation into northerly latitudes, photoperiodically-induced egg diapause enables establishment of Ae. albopictus, and a number of abiotic factors determine the subsequent seasonal activity. The United Kingdom (U.K.) imports over 5 million used tires annually, and this seems the most likely route by which Ae. albopictus would be imported. The anthropophilic and container-breeding nature of Ae. albopictus could cause an urban human biting nuisance and the potential for involvement in (human and veterinary) disease transmission cycles needs to be assessed. This paper addresses the likelihood for importation of Ae. albopictus into the U.K. and assesses, using a Geographic Information Systems (GIS)-based model, the ability for Ae. albopictus to establish, and the likely seasonal activity. It also reviews its possible role as a potential disease vector in the U.K. The model predicts that abiotic risk factors would permit establishment of Ae. albopictus throughout large parts of lowland U.K., with at least four to five months of adult activity (May-September), being more prolonged in the urban centers around London and the southern coastal ports. Pre-emptive surveillance of possible imported Ae. albopictus, through a targeted approach, could prevent the establishment of this exotic mosquito and mitigate any subsequent human and animal health implications for the U.K., either now or in the future.     

Return Customers: Foraging Site Fidelity and the Effect of Environmental Variability in Wide-Ranging Antarctic Fur Seals

Strategies employed by wide-ranging foraging animals involve consideration of habitat quality and predictability and should maximise net energy gain. Fidelity to foraging sites is common in areas of high resource availability or where predictable changes in resource availability occur. However, if resource availability is heterogeneous or unpredictable, as it often is in marine environments, then habitat familiarity may also present ecological benefits to individuals. We examined the winter foraging distribution of female Antarctic fur seals, Arctocephalus gazelle, over four years to assess the degree of foraging site fidelity at two scales; within and between years. On average, between-year fidelity was strong, with most individuals utilising more than half of their annual foraging home range over multiple years. However, fidelity was a bimodal strategy among individuals, with five out of eight animals recording between-year overlap values of greater than 50%, while three animals recorded values of less than 5%. High long-term variance in sea surface temperature, a potential proxy for elevated long-term productivity and prey availability, typified areas of overlap. Within-year foraging site fidelity was weak, indicating that successive trips over the winter target different geographic areas. We suggest that over a season, changes in prey availability are predictable enough for individuals to shift foraging area in response, with limited associated energetic costs. Conversely, over multiple years, the availability of prey resources is less spatially and temporally predictable, increasing the potential costs of shifting foraging area and favouring long-term site fidelity. In a dynamic and patchy environment, multi-year foraging site fidelity may confer a long-term energetic advantage to the individual. Such behaviours that operate at the individual level have evolutionary and ecological implications and are potential drivers of niche specialization and modifiers of intra-specific competition.     

Soil carbon balance following conversion of grassland to oil palm

Oil palm (Elaeis guineensis Jacq.) crops are expanding rapidly in the tropics, with implications for the global carbon cycle. Little is currently known about soil organic carbon (SOC) dynamics following conversion to oil palm and virtually nothing for conversion of grassland. We measured changes in SOC stocks following conversion of tropical grassland to oil palm plantations in Papua New Guinea using a chronosequence of plantations planted over a 25‐year period. We further used carbon isotopes to quantify the loss of grassland‐derived and gain in oil palm‐derived SOC over this period. The grassland and oil palm soils had average SOC stocks of 10.7 and 12.0 kg m^?2, respectively, across all the study sites, to a depth of 1.5 m. In the 0–0.05 m depth interval, 0.79 kg m^?2 of SOC was gained from oil palm inputs over 25 years and approximately the same amount of the original grass‐derived SOC was lost. For the whole soil profile (0–1.5 m), 3.4 kg m^?2 of SOC was gained from oil palm inputs with no significant losses of grass‐derived SOC. The grass‐derived SOC stocks were more resistant to decrease than SOC reported in other studies. Black carbon produced in grassfires could partially but not fully account for the persistence of the original SOC stocks. Oil palm‐derived SOC accumulated more slowly where soil nitrogen contents where high. Forest soils in the same region had smaller carbon stocks than the grasslands. In the majority of cases, conversion of grassland to oil palm plantations in this region resulted in net sequestration of soil organic carbon.     

Quantifying the Contribution of Statins to the Decline in Population Mean Cholesterol by Socioeconomic Group in England 1991 - 2012: A Modelling Study

Background

Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups.

Methods and Findings

This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual ‘no statins’ scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our ‘no statins’ scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men.

Conclusions

Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants.     

Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes

In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes.     

Invasiveness of plants is predicted by size and fecundity in the native range

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