DICER-LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis.

Dicer-like (DCL) enzymes play a pivotal role in RNA silencing in plants, processing the long double-stranded RNA (dsRNA) that triggers silencing into the primary short interfering RNAs (siRNAs) that mediate it. The siRNA population can be augmented and silencing amplified via transitivity, an RNA-dependent RNA polymerase (RDR)-dependent pathway that uses the target RNA as substrate to generate secondary siRNAs. Here we report that Arabidopsis DCL2-but not DCL4-is required for transitivity in cell-autonomous, post-transcriptional silencing of transgenes. An insertion mutation in DCL2 blocked sense transgene-induced silencing and eliminated accumulation of the associated RDR-dependent siRNAs. In hairpin transgene-induced silencing, the dcl2 mutation likewise eliminated accumulation of secondary siRNAs and blocked transitive silencing, but did not block silencing mediated by primary siRNAs. Strikingly, in all cases, the dcl2 mutation eliminated accumulation of all secondary siRNAs, including those generated by other DCL enzymes. In contrast, mutations in DCL4 promoted a dramatic shift to transitive silencing in the case of the hairpin transgene and enhanced silencing induced by the sense transgene. Suppression of hairpin and sense transgene silencing by the P1/HC-Pro and P38 viral suppressors was associated with elimination of secondary siRNA accumulation, but the suppressors did not block processing of the stem of the hairpin transcript into primary siRNAs. Thus, these viral suppressors resemble the dcl2 mutation in their effects on siRNA biogenesis. We conclude that DCL2 plays an essential, as opposed to redundant, role in transitive silencing of transgenes and may play a more important role in silencing of viruses than currently thought

Interaction of CK1δ with γTuSC ensures proper microtubule assembly and spindle positioning.

Casein kinase 1δ (CK1δ) family members associate with microtubule-organizing centers (MTOCs) from yeast to humans, but their mitotic roles and targets have yet to be identified. We show here that budding yeast CK1δ, Hrr25, is a γ-tubulin small complex (γTuSC) binding factor. Moreover, Hrr25's association with γTuSC depends on its kinase activity and its noncatalytic central domain. Loss of Hrr25 kinase activity resulted in assembly of unusually long cytoplasmic microtubules and defects in spindle positioning, consistent with roles in regulation of γTuSC-mediated microtubule nucleation and the Kar9 spindle-positioning pathway, respectively. Hrr25 directly phosphorylated γTuSC proteins in vivo and in vitro, and this phosphorylation promoted γTuSC integrity and activity. Because CK1δ and γTuSC are highly conserved and present at MTOCs in diverse eukaryotes, similar regulatory mechanisms are expected to apply generally in eukaryotes

Dose-response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trial

Objective: To investigate whether a dose-response relationship existed between exercise and subjective sleep quality in postmenopausal women. This objective represents a post hoc assessment that was not previously considered. Design: Parallel-group randomised controlled trial. Setting: Clinical exercise physiology laboratory in Dallas, Texas. Participants: 437 sedentary or overweight/obese postmenopausal women. Intervention: Participants were randomised to one of four treatments, each of 6 months of duration: a non-exercise control treatment (n=92) or one of three dosages of moderate-intensity exercise (50% of VO2peak), designed to meet 50% (n=151), 100% (n=99) or 150% (n=95) of the National Institutes of Health Consensus Development Panel physical activity recommendations. Exercise dosages were structured to elicit energy expenditures of 4, 8 or 12 kilocalories per kilogram of body weight per week (KKW), respectively. Analyses were intent to treat. Primary outcome measures: Continuous scores and odds of having significant sleep disturbance, as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale. Outcome assessors were blinded to participate radomisation assignment. Results: Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group (control: -2.09 (95% CI -4.58 to 0.40), 4 KKW: -3.93 (-5.87 to -1.99), 8 KKW: -4.06 (-6.45 to -1.67), 12 KKW: -6.22 (-8.68 to -3.77); p=0.04), with a significant dose-response trend observed (p=0.02). Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control (4 KKW: OR 0.37 (95% CI 0.19 to 0.73), 8 KKW: 0.36 (0.17 to 0.77), 12 KKW: 0.34 (0.16 to 0.72)). The magnitude of weight loss did not differ between treatment conditions. Improvements in sleep quality were not related to changes in body weight, resting parasympathetic control or cardiorespiratory fitness. Conclusion: Exercise training induced significant improvement in subjective sleep quality in postmenopausal women, with even a low dose of exercise resulting in greatly reduced odds of having significant sleep disturbance

Preparation and ferroelectric properties of (124)-oriented SrBi4Ti4O15 ferroelectric thin film on (110)-oriented LaNiO3 electrode

A (124)-oriented SrBi4Ti4O15 (SBTi) ferroelectric thin film with high volume fraction of {\alpha}SBTi(124)=97% was obtained using a metal organic decomposition process on SiO2/Si substrate coated by (110)-oriented LaNiO3 (LNO) thin film. The remanent polarization and coercive field for (124)-oriented SBTi film are 12.1 {\mu}C/cm2 and 74 kV/cm, respectively. No evident fatigue of (124)-oriented SBTi thin film can be observed after 1{\times}10e9 switching cycles. Besides, the (124)-oriented SBTi film can be uniformly polarized over large areas using a piezoelectric-mode atomic force microscope. Considering that the annealing temperature was 650{\deg}C and the thickness of each deposited layer was merely 30 nm, a long-range epitaxial relationship between SBTi(124) and LNO(110) facets was proposed. The epitaxial relationship was demonstrated based on the crystal structures of SBTi and LNO.Comment: 11 pages, 4 figures, published in Journal of Materials Science: Materials in Electronics (JMSE), 19 (2008), 1031-103

Patterns of Anti-Osteoporosis Medication Use among Women at High Risk of Fracture : Findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture. The GLOW registry follows a cohort of more than 40,000 women aged ≥55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was ≥20%. A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42-0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2-15.5) or osteopenia (HR 4.1, 95% CI 2.9-5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3-2.8). Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition

Patterns of anti-osteoporosis medication use among women at high risk of fracture: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

OBJECTIVE: To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture. METHODS: The GLOW registry follows a cohort of more than 40,000 women aged \u3e /= 55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was \u3e /= 20%. RESULTS: A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42-0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2-15.5) or osteopenia (HR 4.1, 95% CI 2.9-5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3-2.8). CONCLUSIONS: Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition

Heart rate variability and the risk of Parkinson disease: The Atherosclerosis Risk in Communities study: Heart Rate Variability and PD

Autonomic dysfunction frequently occurs in the context of Parkinson’s disease (PD) and may precede onset of motor symptoms. Limited data exist on the prospective association of heart rate variability (HRV), a marker of autonomic function, with PD risk

Magnetic Core Loss of Ultrahigh Strength FeCo Alloys

Hiperco® 50 alloy heat treated between 450 and 650 °C exhibits superior mechanical properties. We report the measurements of the ac core loss at various frequencies up to 4500 Hz of the Hiperco® 50 alloy samples annealed at 450 and 650 °C. The 650 °C annealed specimens have lower ac core loss than the 450 °C annealed ones. The total core loss, consisting of contributions from hysteresis core loss and eddy-current core loss, depends on the frequency f as af+bf2. The eddy current loss of a single laminate is minor compared to the hysteresis loss