A new view on gold speciation in sulfur-bearing hydrothermal fluids from in situ X-ray absorption spectroscopy and quantum-chemical modeling

International audienc

Fall prevention and vitamin D in the elderly: an overview of the key role of the non-bone effects

Preventing falls and fall-related fractures in the elderly is an objective yet to be reached. There is increasing evidence that a supplementation of vitamin D and/or of calcium may reduce the fall and fracture rates. A vitamin D-calcium supplement appears to have a high potential due to its simple application and its low cost. However, published studies have shown conflicting results as some studies failed to show any effect, while others reported a significant decrease of falls and fractures. Through a 15-year literature overview, and after a brief reminder on mechanism of falls in older adults, we reported evidences for a vitamin D action on postural adaptations - i.e., muscles and central nervous system - which may explain the decreased fall and bone fracture rates and we underlined the reasons for differences and controversies between published data. Vitamin D supplementation should thus be integrated into primary and secondary fall prevention strategies in older adults

Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer's Disease: A 7-Year Follow-up

Background. Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. Methods. Four hundred and ninety-eight community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. Results. Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 μg/wk) than nondemented (n = 361; mean intake = 59.0 ± 29.9 μg/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 μg/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). Conclusions. Higher vitamin D dietary intake was associated with a lower risk of developing AD among older wome

SKI2 mediates degradation of RISC 5'-cleavage fragments and prevents secondary siRNA production from miRNA targets in <i>Arabidopsis</i>

Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments

SKI2 mediates degradation of RISC 5′-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis

Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragment

The protein kinase TOUSLED facilitates RNAi in Arabidopsis

RNA silencing is an evolutionarily conserved mechanism triggered by double-stranded RNA that is processed into 21- to 24-nt small interfering (si)RNA or micro (mi)RNA by RNaseIII-like enzymes called Dicers. Gene regulations by RNA silencing have fundamental implications in a large number of biological processes that include antiviral defense, maintenance of genome integrity and the orchestration of cell fates. Although most generic or core components of the various plant small RNA pathways have been likely identified over the past 15 years, factors involved in RNAi regulation through post-translational modifications are just starting to emerge, mostly through forward genetic studies. A genetic screen designed to identify factors required for RNAi in Arabidopsis identified the serine/threonine protein kinase, TOUSLED (TSL). Mutations in TSL affect exogenous and virus-derived siRNA activity in a manner dependent upon its kinase activity. By contrast, despite their pleiotropic developmental phenotype, tsl mutants show no defect in biogenesis or activity of miRNA or endogenous trans-acting siRNA. These data suggest a possible role for TSL phosphorylation in the specific regulation of exogenous and antiviral RNA silencing in Arabidopsis and identify TSL as an intrinsic regulator of RNA interferenc

Emergency Room Evaluation and Recommendations and Risk Screening of Incident Major Neurocognitive Disorders in Older Females: Results of an Observational Population-Based Cohort Study

Background“Emergency Room Evaluation and Recommendations” (ER2) risk levels (i.e., low, moderate and high) may be used to screen for major neurocognitive disorders (MNCD) in older emergency department users, as a high ER2 risk level is associated with MNCD diagnosis. This study aims to examine the association of ER2 risk levels with incident MNCD in community-dwelling older adults.MethodsA total of 709 participants of the EPIDémiologie de l’OStéoporose (EPIDOS) study—an observational population-based cohort study—were recruited in Toulouse (France). ER2 low, moderate and high risk levels were determined at baseline. Incident MNCD and their type (i.e., Alzheimer’s disease (AD) vs. non-AD) were diagnosed after a 7-year follow-up period.ResultsThe overall incidence of MNCD was 29.1%. A low ER2 risk level was associated with low incidence of MNCD [Hazard ratio (HR) = 0.71 with P = 0.018] and AD (HR = 0.56 with P = 0.003), whereas a high risk level, both individually and when combined with a moderate risk level, was associated with high incidence of MNCD (HR ≥ 1.40 with P ≤0.018) and AD (HR ≥ 1.80 with P ≤ 0.003). No association was found with incident non-AD.ConclusionER2 risk levels were positively associated with incident MNCD in EPIDOS participants, suggesting that ER2 may be used for risk screening of MNCD in the older population

Functional characterization of Arabidopsis ARGONAUTE 3 in reproductive tissues

Arabidopsis encodes ten ARGONAUTE (AGO) effectors of RNA silencing, canonically loaded with either 21‐22 nucleotide (nt) long small RNAs (sRNA) to mediate post‐transcriptional‐gene‐silencing (PTGS) or 24nt sRNAs to promote RNA‐directed‐DNA‐methylation. Using full‐locus constructs, we characterized the expression, biochemical properties, and possible modes of action of AGO3. Although AGO3 arose from a recent duplication at the AGO2 locus, their expression patterns differ drastically, with AGO2 being expressed in both male and female gametes whereas AGO3 accumulates in aerial vascular terminations and specifically in chalazal seed integuments. Accordingly, AGO3 down‐regulation alters gene expression in siliques. Similar to AGO2, AGO3 binds sRNAs with a strong 5’‐adenosine bias, but unlike Arabidopsis AGO2, it binds most efficiently 24nt sRNAs. AGO3 immunoprecipitation experiments in siliques revealed that these sRNAs mostly correspond to genes and intergenic regions in a manner reflecting their respective accumulation from their loci‐of‐origin. AGO3 localizes to the cytoplasm and co‐fractionates with polysomes to possibly mediate PTGS via translation inhibition

Applications of random sampling to on-line algorithms in computational geometry

This paper presents a general framework for the design and randomized analysis of geometric algorithms. These algorithms are on-line and the framework provides general bounds for their expected space and time complexities when averaging over all permutations of the input data. The method is general and can be applied to various geometric problems. The power of the technique is illustrated by new efficient on-line algorithms for constructing convex hulls and Voronoi diagrams in any dimension, Voronoi diagrams of line segments in the plane, arrangements of curves in the plane, and others