Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice. Level of α1-Syntrophin and α-Dystrobrevin in Skeletal Muscles of mdx Mice

Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed. We have previously shown the efficiency of mRNA sequence–optimized microdystrophin (ΔR4-23/ΔCT, called MD1) with deletion of spectrin-like repeat domain 4 to 23 and CT domain in ameliorating the pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signalling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain–extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction–induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy.

A novel combined biomarker including plasma carotenoids, vitamin C, and ferric reducing antioxidant power is more strongly associated with fruit and vegetable intake than the individual components

BACKGROUND: Monitoring of fruit and vegetable (F&V) intake is fraught with difficulties. Available dietary assessment methods are associated with considerable error, and the use of biomarkers offers an attractive alternative. Few studies to date have examined the use of plasma biomarkers to monitor or predict the F&V intake of volunteers consuming a wide range of intakes from both habitual F&V and manipulated diets. OBJECTIVE: This study tested the hypothesis that an integrated biomarker calculated from a combination of plasma vitamin C, cholesterol-adjusted carotenoid concentration and Ferric Reducing Antioxidant Power (FRAP) had more power to predict F&V intake than each individual biomarker. METHODS: Data from a randomized controlled dietary intervention study [FLAVURS (Flavonoids University of Reading Study); n = 154] in which the test groups observed sequential increases of 2.3, 3.2, and 4.2 portions of F&Vs every 6 wk across an 18-wk period were used in this study. RESULTS: An integrated plasma biomarker was devised that included plasma vitamin C, total cholesterol-adjusted carotenoids, and FRAP values, which better correlated with F&V intake (r = 0.47, P < 0.001) than the individual biomarkers (r = 0.33, P < 0.01; r = 0.37, P < 0.001; and r = 0.14, respectively; P = 0.099). Inclusion of urinary potassium concentration did not significantly improve the correlation. The integrated plasma biomarker predicted F&V intake more accurately than did plasma total cholesterol-adjusted carotenoid concentration, with the difference being significant at visit 2 (P < 0.001) and with a tendency to be significant at visit 1 (P = 0.07). CONCLUSION: Either plasma total cholesterol-adjusted carotenoid concentration or the integrated biomarker could be used to distinguish between high- and moderate-F&V consumers. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Seasonality of submesoscale flows in the ocean surface boundary layer

A signature of submesoscale flows in the upper ocean is skewness in the distribution of relative vorticity. Expected to result for high Rossby-number flows, such skewness has implications for mixing, dissipation and stratification within the upper ocean. An array of moorings deployed in the Northeast Atlantic for one year as part of the OSMOSIS experiment reveals that relative vorticity is positively skewed during winter even though the scale of the Rossby number is less than 0.5. Furthermore, this skewness is reduced to zero during spring and autumn. There is also evidence of modest seasonal variations in the gradient Rossby number. The proposed mechanism by which relative vorticity is skewed is that the ratio of lateral to vertical buoyancy gradients, as summarized by the inverse gradient Richardson number, restricts its range during winter but less so at other times of the year. These results support recent observations and model simulations suggesting the upper ocean is host to a seasonal cycle in submesoscale turbulence.

Reproducibility of the online Food4Me food-frequency questionnaire for estimating dietary intakes across Europe

Background: Accurate dietary assessment is key to understanding nutrition-related outcomes and is essential for estimating dietary change in nutrition-based interventions. Objective: The objective of this study was to assess the pan-European reproducibility of the Food4Me food-frequency questionnaire (FFQ) in assessing the habitual diet of adults. Methods: Participantsfromthe Food4Me study, a 6-mo,Internet-based, randomizedcontrolled trial of personalized nutrition conducted in the United Kingdom, Ireland, Spain, Netherlands, Germany, Greece, and Poland were included. Screening and baseline data (both collected before commencement of the intervention) were used in the present analyses, and participants were includedonly iftheycompleted FFQs at screeningand at baselinewithin a 1-mo timeframebeforethe commencement oftheintervention. Sociodemographic (e.g., sex andcountry) andlifestyle[e.g.,bodymass index(BMI,inkg/m2)and physical activity] characteristics were collected. Linear regression, correlation coefficients, concordance (percentage) in quartile classification, and Bland-Altman plots for daily intakes were used to assess reproducibility. Results: In total, 567 participants (59% female), with a mean 6 SD age of 38.7 6 13.4 y and BMI of 25.4 6 4.8, completed bothFFQswithin 1 mo(mean 6 SD: 19.26 6.2d).Exact plus adjacent classification oftotal energy intakeinparticipants was highest in Ireland (94%) and lowest in Poland (81%). Spearman correlation coefficients (r) in total energy intake between FFQs ranged from 0.50 for obese participants to 0.68 and 0.60 in normal-weight and overweight participants, respectively. Bland-Altman plots showed a mean difference between FFQs of 210 kcal/d, with the agreement deteriorating as energy intakes increased. There was little variation in reproducibility of total energy intakes between sex and age groups. Conclusions: The online Food4Me FFQ was shown to be reproducible across 7 European countries when administered within a 1-mo period to a large number of participants. The results support the utility of the online Food4Me FFQ as a reproducible tool across multiple European populations. This trial was registered at clinicaltrials.gov as NCT01530139.

George Sand : une femme moderne ?

A travers des œuvres de George Sand (1804-1876), le mémoire étudie la littérature champêtre, l'exotisme et l’écriture féminine. Dans un deuxième temps il montre les relations avec des personnes célèbres qui ont influencé l’auteur et les correspondances entretenues entre George Sand et elles. Enfin le mémoire se termine par une étude de la femme moderne qu'était George Sand.

Photography and christian mission: George Brown`s images of the New Britain mission 1875-80

In 1875, Methodist George Brown arrived in the Bismarck Archipelago to establish the New Britain Mission. Based in the Duke of York Islands, Brown's territory covered New Ireland and the Gazelle Peninsula of New Britain. The mission was one of the first to be photographed from its inception. The Australian Museum holds 96 plates from the first five years of the mission. Brown's photographs are a visual record of conditions and peoples of the time. Analysed in relation to Brown's writings they are indicative of the relationships and bonds established through photography both in the mission field and across wider scientific and church audiences. The methodology employed here also challenges the kinds of interpretations of photographs that can arise from visual analyses relying solely on the caption and the posing of the subject.

Sir George Simpson : 19th century fur trade governor and precursor of systematic management

Purpose – Sir George Simpson, the Governor of the Hudson's Bay Company (HBC) from 1821 to his death in 1860, was the subject of numerous biographical works that described various facets of the man including his managerial abilities, literary prowess, physical stamina, abundant energy, extensive art collection and ethnological specimens. Two related aspects of his outstanding management style have been overlooked: the genesis of his management style and where it can be placed in the evolution of management practices during the 19th century.

Design/methodology/approach – Primary data from the Hudson's Bay Company archives plus secondary sources.

Findings – Simpson's management abilities came from his grammar school education and his apprenticeship to a counting house. More importantly, it can be attributed to his association with his mentor Andrew Wedderburn, his dedication to the HBC, and his high level of physical and intellectual energy. His information intensive management style was also a significant precursor to systematic management, which occurred later in the 19th century.

Research limitations/implications – Future research should examine other examples of the evolution of management during the 19th century, particularly the transition from sub-unit accountability to systematic management.

Originality/value – The paper emphasizes the importance of managers in making management systems work.