HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3' terminal nucleotide.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) in plants bear a methyl group on the ribose of the 3' terminal nucleotide. We showed previously that the methylation of miRNAs and siRNAs requires the protein HEN1 in vivo and that purified HEN1 protein methylates miRNA/miRNA* duplexes in vitro. In this study, we show that HEN1 methylates both miRNA/miRNA* and siRNA/siRNA* duplexes in vitro with a preference for 21-24 nt RNA duplexes with 2 nt overhangs. We also demonstrate that HEN1 deposits the methyl group on to the 2' OH of the 3' terminal nucleotide. Among various modifications that can occur on the ribose of the terminal nucleotide, such as 2'-deoxy, 3'-deoxy, 2'-O-methyl and 3'-O-methyl, only 2'-O-methyl on a small RNA inhibits the activity of yeast poly(A) polymerase (PAP). These findings indicate that HEN1 specifically methylates miRNAs and siRNAs and implicate the importance of the 2'-O-methyl group in the biology of RNA silencing

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

Exceptional high Seebeck Coefficient and Gas-Flow-Induced Voltage in Multilayer Graphene

Monolayer graphene shows Seebeck coefficient several times and gas-flow-induced voltage twenty times higher than that of bulk graphite. Here we find that the Seebeck coefficient of multilayer graphene increases monotonically with increasing layer and reaches its peak value at hexa-layer ~77% higher than for monolayer and then decreases, although the electric resistance decreases monotonically with increasing layer. The flow-induced voltage is significantly higher in 2, 4, 5, 6, 7 layered graphene than in 1, 3, 8 layered one, against the prevailing view that it should be proportional to Seebeck coefficient. These thickness effects are also in sharp contrast to that in continuous aluminum nanofilms.Comment: 5 figures,20pages,conferenc

Cortical gray and subcortical white matter associations in Parkinson's disease

Cortical atrophy has been documented in both Parkinson’s disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline, 18-, and 36-months, from which cortical volumes and underlying subcortical white matter axial (AD), radial (RD) diffusivities, and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (Ps ≤0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (Ps ≤ 0.0013) in two subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD

Using a technology-based intervention to promote weight loss in sedentary overweight or obese adults: a randomized controlled trial study design

Purpose: The SenseWearTM Armband is an activity monitor developed to improve lifestyle self-monitoring. Currently, few studies assess electronic self-monitoring and weight loss with a lifestyle intervention program. To our knowledge, only one study has used the SenseWear Armband in combination with a lifestyle intervention to improve weight loss, and no studies have evaluated whether a self-monitoring intervention based solely on the armband can promote weight loss. Consequently, the aims of the study were to assess weight loss from electronic self-monitoring, to compare these values to the lifestyle intervention and standard care groups, and to compare weight loss with lifestyle intervention with and without the armband. Patients and methods: We recruited 197 sedentary overweight or obese adults (age, 46.8 ± 10.8 years; BMI, 33.3 ± 5.2 kg/m2) to participate in the 9-month study. Participants were randomized into one of four weight loss groups: 1) the standard care group received a self-directed weight loss program, complete with an evidence-based weight loss manual (standard care, n = 50); 2) a 14-week group-based behavioral weight loss program followed by weekly, biweekly, and monthly telephone counseling calls (GWL, n = 49); 3) the use of the armband to help improve lifestyle self-monitoring (SWA alone, n = 49); or (4) the group-based behavioral weight loss program and follow-up telephone counseling calls plus the armband (GWL + SWA, n = 49). All participants received the evidence-based weight loss manual at baseline. All measures were performed at baseline and months 4 and 9. The primary outcomes were weight loss and waist circumference reduction. Results: This study is a well-designed randomized controlled study powered to detect a 0.5-kg weight loss and 0.6-cm waist circumference reduction in overweight and obese sedentary adults. Conclusion: Innovative technologies are providing lifestyle self-monitoring and weight loss tools. Utilizing these technologies may be an important step in improving the current obesity epidemic

The Breakdown of the Fingerprinting of Vortices by Hysteresis Loops in Circular Multilayer Ring Arrays

Microscale single-layer ferromagnetic rings typically exhibit a magnetic vortex state at remanence, characterized by a flux-closed magnetic state with zero stray fields. Magnetic reversal in such systems yields a vanishing remanent magnetization. In contrast, the authors show that in individual layers in thin rings, which alternate magnetic and nonmagnetic materials (NiFe/Cu/Co), layer-resolved hysteresis loops, measured using x-ray resonant magnetic scattering, exhibit the characteristics of a vortex formation, although photoelectron emission microscopy and micromagnetic simulations clearly prove that multidomain states are formed. This result is of considerable importance for the development of pseudo-spin-valve-type structures for applications

The Breakdown of the Fingerprinting of Vortices by Hysteresis Loops in Circular Multilayer Ring Arrays

Microscale single-layer ferromagnetic rings typically exhibit a magnetic vortex state at remanence, characterized by a flux-closed magnetic state with zero stray fields. Magnetic reversal in such systems yields a vanishing remanent magnetization. In contrast, the authors show that in individual layers in thin rings, which alternate magnetic and nonmagnetic materials (NiFe/Cu/Co), layer-resolved hysteresis loops, measured using x-ray resonant magnetic scattering, exhibit the characteristics of a vortex formation, although photoelectron emission microscopy and micromagnetic simulations clearly prove that multidomain states are formed. This result is of considerable importance for the development of pseudo-spin-valve-type structures for applications

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity. Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, 5 years [PDL, n = 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n = 87, control n = 66) to validate our findings. In the longitudinal cohort, PDL had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p < 0.05). Longitudinally, loss of gyrification was accelerated in PDM participants, compared to controls. LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample. Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo

Association between muscular strength and mortality in men: prospective cohort study

Objective: To examine prospectively the association between muscular strength and mortality from all causes, cardiovascular disease, and cancer in men. Design: Prospective cohort study. Setting: Aerobics center longitudinal study. Participants: 8762 men aged 20-80. Main outcome measures: All cause mortality up to 31 December 2003; muscular strength, quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill. Results: During an average follow-up of 18.9 years, 503 deaths occurred (145 cardiovascular disease, 199 cancer). Age adjusted death rates per 10,000 person years across incremental thirds of muscular strength were 38.9, 25.9, and 26.6 for all causes; 12.1, 7.6, and 6.6 for cardiovascular disease; and 6.1, 4.9, and 4.2 for cancer (all P Conclusion: Muscular strength is inversely and independently associated with death from all causes and cancer in men, even after adjusting for cardiorespiratory fitness and other potential confounders

Electronic feedback in a diet- and physical activity-based lifestyle intervention for weight loss: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The SenseWear™ Armband (SWA) (BodyMedia, Inc. Pittsburgh, PA) is a physical activity and lifestyle monitor that objectively and accurately measures free-living energy balance and sleep and includes software for self-monitoring of daily energy expenditure and energy intake. The real-time feedback of the SWA can improve individual self-monitoring and, therefore, enhance weight loss outcomes.</p> <p>Methods</p> <p>We recruited 197 sedentary overweight or obese adults (age, 46.8 ± 10.8 y; body mass index (BMI), 33.3 ± 5.2 kg/m²; 81% women, 32% African-American) from the greater Columbia, South Carolina area. Participants were randomized into 1 of 4 groups, a self-directed weight loss program via an evidence-based weight loss manual (Standard Care, n = 50), a group-based behavioral weight loss program (GWL, n = 49), the armband alone (SWA-alone, n = 49), or the GWL plus the armband (GWL+SWA, n = 49), during the 9-month intervention. The primary outcome was change in body weight and waist circumference. A mixed-model repeated-measures analysis compared change in the intervention groups to the standard care group on weight and waist circumference status after adjusting for age, sex, race, education, energy expenditure, and recruitment wave.</p> <p>Results</p> <p>Body weight was available for 62% of participants at 9 months (52% standard care, 70% intervention). There was significant weight loss in all 3 intervention groups (GWL, 1.86 kg, P = 0.05; SWA-alone, 3.55 kg, P = 0.0002; GWL+SWA, 6.59 kg, P < 0.0001) but not in the Standard Care group (0.89 kg, P = 0.39) at month 9. Only the GWL+SWA group achieved significant weight loss at month 9 compared to the Standard Care group (P = 0.04). Significant waist circumference reductions were achieved in all 4 groups at month 9 (Standard Care, 3.49 cm, P = 0.0004; GWL, 2.42 cm, P = 0.008; SWA-alone, 3.59 cm, P < 0.0001; GWL+SWA, 6.77 cm, P < 0.0001), but no intervention group had significantly reduced waist circumference compared to the Standard Care group.</p> <p>Conclusions</p> <p>Continuous self-monitoring from wearable technology with real-time feedback may be particularly useful to enhance lifestyle changes that promote weight loss in sedentary overweight or obese adults. This strategy, combined with a group-based behavioral intervention, may yield optimal weight loss.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00957008">NCT00957008</a></p