Wellbeing Notebook - Pen and Paper: A Simple Formula for Enhancing Wellbeing

Sitting in her classroom, Lynn wonders whether her pen pal, Jean, has received and read her letter. Several kilometres away, sitting in her armchair, Jean’s eyes light up as she reads the questions that Lynn has carefully written. She takes up a pen and begins to write. Theirs is a mutually beneficial relationship established through pen and paper, with the help of an envelope and an enthusiastic teacher who acted as a courier

Fructans redistribution prior to sprouting in stored onion bulbs is a potential marker for dormancy break

Continuous supply of high quality onion bulbs to meet year-round demand is dependent on maintaining dormancy and bulb quality during storage. Sprouting impacts negatively on the storage quality of onion bulbs. Ethylene supplementation has previously been revealed to inhibit sprout growth in stored onion bulbs. Fructans content, especially those at higher degree of polymerisation (DP), are reported to positively correlate with delayed sprouting. However, little is known about the impact of pre-harvest irrigation regimes on fructans accumulation and redistribution in relation to onion bulb dormancy and quality in store. Across two seasons, onion plants of cultivars ‘Red Baron’ and ‘Sherpa’ were subjected to full irrigation (FI) (100% replenishment of crop evapotranspiration) or deficit irrigation (DI) (50% of FI treatment) from bulb initiation to harvest. Bulbs were harvested at full maturity and stored at 1 °C for five months. Bulbs were treated with or without 1-MCP (1 μL L−1) for 24 h before storage under continuous ethylene supplementation (10 μL L−1) or air. DI had no effect on dormancy-break, sprout emergence, total fructans content and total sugar content. In contrast, ethylene delayed sprout emergence and suppressed sprout growth; added 1-MCP enhanced this effect. The concentration of DP3-8 fructans were higher in top and bottom sections compared to the baseplate. Before sprout emergence, fructans of DPs 7–8 were no longer present in the top and bottom wedges, while they accumulated in the baseplate; irrespective of pre- or postharvest treatments. This redistribution of fructans within the bulb suggested a transition in dormancy state and could be used as a predictive marker for sprouting in stored onion bulbs

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

AGB Sodium Abundances in the Globular Cluster 47 Tucanae (NGC 104)

A recent analysis comparing the [Na/Fe] distributions of red giant branch (RGB) and asymptotic giant branch (AGB) stars in the Galactic globular cluster NGC 6752 found that the ratio of Na-poor to Na-rich stars changes from 30:70 on the RGB to 100:0 on the AGB. The surprising paucity of Na-rich stars on the AGB in NGC 6752 warrants additional investigations to determine if the failure of a significant fraction of stars to ascend the AGB is an attribute common to all globular clusters. Therefore, we present radial velocities, [Fe/H], and [Na/Fe] abundances for 35 AGB stars in the Galactic globular cluster 47 Tucanae (47 Tuc; NGC 104), and compare the AGB [Na/Fe] distribution with a similar RGB sample published previously. The abundances and velocities were derived from high resolution spectra obtained with the Michigan/Magellan Fiber System (M2FS) and MSpec spectrograph on the Magellan-Clay 6.5m telescope. We find the average heliocentric radial velocity and [Fe/H] values to be =-18.56 km s^-1 (sigma=10.21 km s^-1) and =-0.68 (sigma=0.08), respectively, in agreement with previous literature estimates. The average [Na/Fe] abundance is 0.12 dex lower in the 47 Tuc AGB sample compared to the RGB sample, and the ratio of Na-poor to Na-rich stars is 63:37 on the AGB and 45:55 on the RGB. However, in contrast to NGC 6752, the two 47 Tuc populations have nearly identical [Na/Fe] dispersion and interquartile range values. The data presented here suggest that only a small fraction <20% of Na-rich stars in 47 Tuc may fail to ascend the AGB. Regardless of the cause for the lower average [Na/Fe] abundance in AGB stars, we find that Na-poor stars and at least some Na-rich stars in 47 Tuc evolve through the early AGB phase. [abridged]Comment: Accepted for publication in the Astronomical Journal; 15 pages; 8 figures; 4 table

Open-ocean submesoscale motions: a full seasonal cycle of mixed layer instabilities from gliders

The importance of submesoscale instabilities, particularly mixed-layer baroclinic instability and symmetric instability, on upper ocean mixing and energetics is well documented in regions of strong, persistent fronts such as the Kuroshio and the Gulf Stream. Less attention has been devoted to studying submesoscale flows in the open ocean, far from long-term mean geostrophic fronts, characteristic of a large proportion of the global ocean. We present a year-long, submesoscale-resolving time series of near-surface buoyancy gradients, potential vorticity and instability characteristics, collected by ocean gliders, that provides insight into open-ocean submesoscale dynamics over a full annual cycle. The gliders continuously sampled a 225 km2 region in the subtropical northeast Atlantic, measuring temperature, salinity and pressure along 292 short (\~{}20 km) hydrographic sections.Glider observations show a seasonal cycle in near-surface stratification. Throughout the fall (September through November), the mixed layer deepens, predominantly through gravitational instability, indicating that surface cooling dominates submesoscale restratification processes. During winter (December through March), mixed layer depths are more variable, and estimates of the balanced Richardson number, which measures the relative importance of lateral and vertical buoyancy gradients, depict conditions favorable to symmetric instability. The importance of mixed layer instabilities on the restratification of the mixed layer, as compared with surface heating and cooling, shows that submesoscale processes can reverse the sign of an equivalent heat flux up to 25{\%} of the time during winter. These results demonstrate that the open-ocean mixed layer hosts various forced and unforced instabilities, which become more prevalent during winter, and emphasize that accurate parameterizations of submesoscale processes are needed throughout the ocean

Focused Ion Beam Fabrication

Contains reports on five research projects.DARPA/Naval Electronic Systems Command (Contract MDA-903-85-C-0215)Charles Stark Draper Laboratory (Contract DL-H-261827)U.S. Navy - Office of Naval Research (Contract N00014-84-K-0073)Nippon Telephone and TelegraphHitachi Central Research Laborator

Effects of Gabapentin and Pregabalin on Calcium Homeostasis: Implications for Physical Rehabilitation of Musculoskeletal Tissues

Purpose of review: In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system. Recent findings: Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α2δ1 auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α2δ1 subunit where GBP and PGB can alter calcium-mediated signaling events. In tissues such as bone, muscle, and cartilage, α2δ1 has important roles in skeletal formation, mechanosensation, and normal tissue function/repair that may be affected by chronic use of gabapentinoids. Long-term use of gabapentinoids is associated with detrimental musculoskeletal outcomes, including increased fracture risk. Therefore, understanding potential complications is essential for clinicians to guide appropriate treatments

Guidance for the assessment of risks to bees from the use of plant protection products applied as seed coating and soil applications – conclusions of the ICPBR dedicated working group

contribution to session IRegulatory issuesBackground: Soil or seed applied plant protection products (PPPs) aim at bringing the amount of active substance involved to the only parts of the plant that have to be protected. Despite a reduced exposure of non target organisms by this way, an exposure of honey bees through residues in pollen and/or nectar may not be excluded for substances that migrate towards the upper plant parts. Directive 91/414/EEC, related guidance documents and literature data were reviewed and discussed by a working group of the ICPBR (International Commission for Plant-Bee Relationships) with the aim to provide adequate guidance to proceed in a risk assessment in such cases.Results: The review and expert knowledge collected within ecotoxicology, entomology and plant residue area allowed to identify the key parameters that trigger a risk assessment as well as basic hypotheses to consider in deciding for the experimentations required (laboratory, semi-field and field tests). A stepwise, tiered approach is proposed, which has been checked for its ability to discriminate substances that may pose a risk to bees from substances of low concern. Conclusion: The present scheme is proposed to update the current EPPO risk assessment scheme with a special issue on systemic PPPs.Keywords: risk assessment, honey bees, soil or seed treatments, systemic

Environmental risk assessment scheme for plant protection products - Chapter 10: Honeybees – Proposed scheme

contribution to session I Regulatory issue