RNA silencing in plants: Flash report!

Earlier this year plant scientists met in Santa Fe, New Mexico at the Keystone Symposium "RNA Silencing Mechanisms in Plants". Sessions included small RNA biogenesis and signalling, development and stress responses, small RNA-directed DNA methylation, and interaction with pathogens. This report highlights some of the prominent and recurring themes at the meeting and emerging arenas of future research.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio

The ATP:ADP ratio is a critical parameter of cellular energy status that regulates many metabolic activities. Here we report an optimized genetically-encoded fluorescent biosensor, PercevalHR, that senses the ATP:ADP ratio. PercevalHR is tuned to the range of intracellular ATP:ADP expected in mammalian cells, and it can be used with one- or two-photon microscopy in live samples. We use PercevalHR to visualize activity-dependent changes in ATP:ADP when neurons are exposed to multiple stimuli, demonstrating that it is a sensitive reporter of physiological changes in energy consumption and production. We also use PercevalHR to visualize intracellular ATP:ADP while simultaneously recording currents from ATP-sensitive potassium (KATP) channels in single cells, showing that PercevalHR enables the study of coordinated variation in ATP:ADP and KATP channel open probability in intact cells. With its ability to monitor changes in cellular energetics within seconds, PercevalHR should be a versatile tool for metabolic research

Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression

Background Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment. Methods Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period. Results Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42). Conclusions These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.Psycholog

ENHANCING CHEMOTHERAPEUTIC EFFICACY OF DOXORUBICIN THROUGH COMBINATION THERAPY WITH RAPAMYCIN AND SILDENAFIL, WHILE PROVIDING CARDIOPROTECTION IN BREAST CANCER MODELS

Doxorubicin (DOX) is a common chemo-drug for breast cancer, but it causes severe cardiotoxicity. This study explores combining Sildenafil (Sild) and Rapamycin (Rapa), which inhibit phosphodiesterase-5 (PDE5) and mTOR, respectively, to boost DOX’s anticancer, but provide cardioprotection. Triple negative human (MDA-MB-231) and murine (4T1) breast cancer cells were treated with DOX (1 µM) with/without Rapa (100 nM) and Sild (10 µM) for 24-72 hours to analyze cell death, cell viability assays and protein expression. Human epidermal growth factor receptor 2-positive breast cancer (SKBr3) spheroids were treated with the same concentrations of DOX and/or AG825 (5µM) with/without Rapa and/or Sild for 48 hours, followed by 48 hours incubation in fresh medium. The SKBr3 medium was used to treat human cardiomyocytes (AC16) for 48 hours to evaluate cardioprotection. Sild and Rapa combination enhanced DOX-induced killing of all three-breast cancer cells, suppressed mTOR signaling and Bcl2 expression, and increased cleaved PARP in cancer cells, while reducing cardiomyocyte death compared to individual treatment. Adult female C57/B6 mice were treated with DOX (6 mg/kg/twice weekly) for 2 weeks followed by Afatinib (10 mg/kg, oral gavage, 5 days/week) for 2 weeks with/without Rapa (0.25 mg/kg/day) and Sild (1.4 mg/kg/day). After 12 weeks, the combination alleviated DOX+Afatinib-induced cardiac dysfunction with improvement of survival and body weight. This study manifests a unique combination with Sild and Rapa, enhancing chemotherapy efficacy, while safeguarding cardiac function, representing a promising advancement for breast cancer chemo-immunotherapy strategy

Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression

Background Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment. Methods Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period. Results Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42). Conclusions These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.Psycholog

Skill assessment in upper limb myoelectric prosthesis users: Validation of a clinically feasible method for characterising upper limb temporal and amplitude variability during the performance of functional tasks

Upper limb myoelectric prostheses remain challenging to use and are often abandoned. A proficient user must be able to plan/execute arm movements while activating the residual muscle(s), accounting for delays and unpredictability in prosthesis response. There is no validated, low cost measure of skill in performing such actions. Trial-trial variability of joint angle trajectories measured during functional task performance, linearly normalised by time, shows promise. However, linear normalisation of time introduces errors, and expensive camera systems are required for joint angle measurements. This study investigated whether trial-trial variability, assessed using dynamic time warping (DTW)of limb segment acceleration measured during functional task performance, is a valid measure of user skill. Temporal and amplitude variability of forearm accelerations were determined in 1) seven myoelectric prosthesis users and six anatomically-intact controls and 2) seven anatomically-intact subjects learning to use a prosthesis simulator over repeated sessions. 1: temporal variability showed clear group differences (p<0.05). 2: temporal variability considerably increased on first use of a prosthesis simulator, then declined with training (both p<0.05). Amplitude variability showed less obvious differences. Analysing forearm accelerations using DTW appears to be a valid low-cost method for quantifying movement quality of upper limb prosthesis use during goal-oriented task performance

Influence of Nutrient Source on Yield, Quality and Economics of Seed Production in Vegetable Cowpea (Vigna unguiculata ssp. sesquipedalis)

Field investigation was carried out to study the influence of different sources of nutrients on seed production in vegetable cowpea (Vigna unguiculata&nbsp;ssp.&nbsp;sesquipedalis) during 2010-11 in Randomized Block Design, with twelve combinations of nutrient sources. Results showed significant variation in seed yield potential in the crop. Highest seed yield (435.97kg ha-1) was recorded in the treatment where recommended NPK dose for the seed crop was applied along with vermicompost at 50 per cent nitrogen substitution. Yield attributes were found non-significant, but had a positive influence on seed yield. Germination percentage and 100-seed weight was significantly higher in treatments receiving a combination of vermicompost and poultry manure. Benefit:Cost analysis revealed that 50 per cent N substitution with vermicompost and 25% N with poultry manure were the most profitable in cowpea seed production

Education and Decision Making at the Time of Triptan Prescribing: Patient Expectations vs Actual Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106941/1/head12308.pd

Collaborative Learning: Building English Learning Communities

application/pdfdepartmental bulletin pape

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.Brain & Behavior Research Foundation (Young Investigator Award)JPB Foundatio