Note sur le tombeau d'Odilon, sire de Mercoeur, conservé au Musée municipal de Turin,

"Extrait du t. XXXII des Annales de la Société d'agriculture, sciences, arts et commerce du Puy".

Water regulation of actinomycin-D binding to DNA: the interplay among drug affinity, DNA long-range conformation, and hydration

Actiaomycin-D (actD) binds to natural DNA at two different classes of binding sites, weak and strong. The affinity for these sites is highly dependent on DNA se(sequence and solution conditions, and the interaction appears to be purely entropic driven Although the entropic character of this reaction has been attributed to the release of water molecules upon drug to DNA complex formation, the mechanism by which hydration regulates actD binding and discrimination between different classes of binding sites on natural DNA is still unknown. In this work, we investigate the role of hydration on this reaction using the osmotic stress method. We skew that the decrease of solution water activity, due to the addition of sucrose, glycerol ethylene glycol, and betaine, favors drug binding to the strong binding sites on DNA by increasing both the apparent binding affinity Delta G, and the number of DNA base pairs apparently occupied by the bound drug n(bp/actD). These binding parameters vary linearly with the logarithm of the molar fraction of water in solution log(X-w), which indicates the contribution of water binding to the energetic of the reaction. It is demonstrated that the hydration change measured upon binding increases proportionally to the apparent size of the binding site n(bp/uctD). This indicates that n(bp/actD) measured from the Scatchard plod is a measure of the size of the DNA molecule changing conformation due to ligand binding. We also find that the contribution of DNA deformation, gauged by n(bp/act) to the total free energy of binding Delta G, is given by Delta G = Delta G(local) + n(bp/actD) x delta G(DNA), where Delta G(local), = -8020 +/- 51 cal/mol of actD bound and delta G(DNa) = -24.1 +/- 1.7cal/mol of base pair at 25 degrees C. We interpret Delta G(local), as the energetic contribution due to the direct interactions of actD with the actual tetranucleotide binding site, and it n(bp/actB) X delta G(DNA) as that due to change inconformation, induced by binding, of it n(bp/actD) DNA base pairs flanking the local site. This interpretation is supported by the agreement found between the value of delta G(DNA) and the torsional free energy change measured independently. We conclude suggesting an allosteric model for ligand binding to DNA, such that the increase in binding affinity is achieved by increasing the relaxation of the unfavorable free energy of binding storage at the local site through a larger number of DNA base pairs. The new aspect on this model is that the size of the complex is not fixed but determined by solutions conditions, such as water activity, which modulate the energetic barrier to change helix conformation. These results may suggest that long-range allosteric transitions of duplex DNA are involved in the inhibition of RNA synthesis by actD, and more generally, in the regulation of transcription. (C) 2000 John Wiley & Sons, Inc.

Genetic diversity in wild (Sus scrofa scrofa) and domestic (Sus scrofa domestica) pigs and their hybrids based on polymorphism of a fragment of the D-loop region in the mitochondrial DNA

We examined the variation in mitochondrial DNA by sequencing the D-loop region in wild and domestic (large-white breed) pigs, in hybrids between domestic and wild pigs, and in Monteiro pigs. A D-loop fragment of approximately 330 bp was amplified by PCR. Sequencing of DNA amplicons identified haplotypes previously described as European and Asian types. Monteiro pigs and wild pigs had European haplotypes and domestic pigs had both European and Asian haplotypes. ©FUNPEC-RP.

Paleoceanographic record since 13kyr BP of sediment core LaPAS-KF02

In this paper we present a paleoceanographic reconstruction of the southwestern South Atlantic for the past 13 kyr based on faunal and isotopic analysis of planktonic foraminifera from a high-resolution core retrieved at the South Brazil Bight continental slope. Our record indicates that oceanographic changes in the southwestern South Atlantic during the onset of the Holocene were comparable in strength to those that occurred during the Younger Dryas. Full interglacial conditions started abruptly after 8.2 kyr BP with a sharp change in faunal composition and surface hydrography (SST and SSS). Part of the observed events may be explained in terms of changes in thermohaline circulation while the other part suggests a dominant role of winds. Our data indicate that during the Early Holocene upwelling was significantly strengthened in the South Brazil Bight promoting high productivity and preventing the establishment of the typically interglacial menardiiform species. In general terms, oceanographic changes recorded by core KF02 occurred in synchrony with Antarctica's climate.

Lithic economy and territory of Epipaleolithic hunter–gatherers in the Middle Tagus: The case of Pena d'Água (Portugal)

In Central Portugal (westernmost Eurasia) the transition from the traditional Pleistocene hunter–gatherer societies to the complex Mesolithic societies of the Holocene has been debated for decades. While some argue that these differences were a progressive phenomenon that started with the shift from the Pleistocene to the Holocene, others defend that the Late Pleistocene patterns were fairly similar to those of the Epipaleolithic and that the major shift was rapid, dramatic and triggered by the necessary adaptation to the 8.2 ka cal BP (8.09–8.25 ka cal BP) climatic event. The study of lithic raw material provenance might be useful for this discussion, since it has been suggested that the Magdalenian and Epipaleolithic populations from this region were collecting this resources within a close range territory, whereas the Mesolithic populations were acquiring them at longer distances. In this paper, we present the results from p-XRF, VP-SEM-EDS and μ-XRD analysis done on the Epipaleolithic lithic assemblage from Pena d'Água Rockshelter, and in some geological samples from secondary sources located ∼14 km from this site. This layer is of major relevance for this debate since it is dated from 8.19 ka cal BP. If the transition was gradual, it would be expected that this assemblage would show some traits of higher-complexity seen in the Mesolithic, namely of longer distance acquisition. However, our results indicate correspondence between the archaeological chert types and some of the geological sources. The differences seen between the archaeological specimens and geological samples are mostly present in traits that can be related with manufacture, handling and post-depositional phenomena. The results suggest that, in what concerns to the economy of abiotic resources, the Epipaleolithic populations living at the time of the dramatic 8.2 ka cal BP cold event, were performing a short range acquisition of lithic raw materials which reinforces the idea of continuity from the Late Pleistocene to the 8.2 ka cal BP event and an abrupt and dramatic shift soon after this phenomena.

Knowledge about health benefits of Vitamin D in Queensland Australia

In Queensland, Australia, the ultraviolet (UV) radiation levels are high (greater than UV Index 3) almost all year round. Although ambient UV is about three times higher in summer compared to winter, Queensland residents receive approximately equal personal doses of UV radiation within these seasons (Neale et al., 2010). Sun protection messages throughout the year are thus essential (Montague et al., 2001), need to reach all segments of the population, and should incorporate guidelines for maintenance of adequate vitamin D levels. Knowledge is an essential requirement to allow people to make health conscious decisions. Unprompted knowledge commonly requires a higher level of awareness or recency of acquisition compared to prompted recall (Waller et al., 2004). This paper thus reports further on the data from a 2008 population-based, cross-sectional telephone survey conducted in Queensland, Australia (2,001 participants; response rate=45%) (Youl et al., 2009). It was the aim of this research to establish the level of, and factors predicting, unprompted and prompted knowledge about health and vitamin D.

Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis

Summary This systematic review demonstrates that vitamin D supplementation does not have a significant effect on muscle strength in vitamin D replete adults. However, a limited number of studies demonstrate an increase in proximal muscle strength in adults with vitamin D deficiency. Introduction The purpose of this study is to systematically review the evidence on the effect of vitamin D supplementation on muscle strength in adults. Methods A comprehensive systematic database search was performed. Inclusion criteria included randomised controlled trials (RCTs) involving adult human participants. All forms and doses of vitamin D supplementation with or without calcium supplementation were included compared with placebo or standard care. Outcome measures included evaluation of strength. Outcomes were compared by calculating standardised mean difference (SMD) and 95% confidence intervals. Results Of 52 identified studies, 17 RCTs involving 5,072 participants met the inclusion criteria. Meta-analysis showed no significant effect of vitamin D supplementation on grip strength (SMD −0.02, 95%CI −0.15,0.11) or proximal lower limb strength (SMD 0.1, 95%CI −0.01,0.22) in adults with 25(OH)D levels >25 nmol/L. Pooled data from two studies in vitamin D deficient participants (25(OH)D <25 nmol/L) demonstrated a large effect of vitamin D supplementation on hip muscle strength (SMD 3.52, 95%CI 2.18, 4.85). Conclusion Based on studies included in this systematic review, vitamin D supplementation does not have a significant effect on muscle strength in adults with baseline 25(OH)D >25 nmol/L. However, a limited number of studies demonstrate an increase in proximal muscle strength in adults with vitamin D deficiency. Keywords Muscle – Muscle fibre – Strength – Vitamin D

Retrospective evaluation and prospective value-add : a review of R&D investment in Australia

This paper describes a lead project currently underway through Australia’s Sustainable Built Environment National Research Centre evaluating diffusion mechanisms and impacts of R&D investment in the Australian built environment. Through a retrospective analysis of R&D investment trends and industry outcomes, and a prospective assessment of industry futures using strategic foresighting, a future-focussed industry R&D roadmap and pursuant policy guidelines will be developed. This research aims to build new understandings and knowledge relevant to R&D funding strategies, research team formation and management, dissemination of outcomes and industry uptake. Each of these issues are critical due to: the disaggregated nature of the built environment industry; intense competition; limited R&D investment; and new challenges (e.g. IT, increased environmental expectations). This paper details the context within which this project is being undertaken and the research design. Findings of the retrospective analysis of past R&D investment in Australia will be presented at this conference.

Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base. Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design. Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up. Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events). Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3. Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D. Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively. Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level. Copyright © 2012 by The Endocrine Society.

A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P= 0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 μg/week ( ≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).

Clinical outcomes of vitamin D deficiency and supplementation in cancer patients

Results of recent studies suggest that circulating levels of vitamin D may play an important role in cancer-specific outcomes. The present systematic review was undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association between circulating calcidiol (the indicator of vitamin D status) and clinical outcomes. A systematic search of original, peer-reviewed studies on calcidiol at cancer diagnosis, and throughout treatment and survival, was conducted yielding 4,706 studies. A total of 37 studies met the inclusion criteria for this review. Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to 31% of patients identified as deficient and 67% as insufficient. The efficacy of cholecalciferol supplementation for raising the concentration of circulating calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not be sufficient to maintain adequate concentrations or prevent decreasing calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and survival outcomes in cancer patients are lacking.