Observing object lifting errors modulates cortico-spinal excitability and improves object lifting performance.

PublishedJournal ArticleObserving the actions of others has been shown to modulate cortico-spinal excitability and affect behaviour. However, the sensorimotor consequences of observing errors are not well understood. Here, participants watched actors lift identically weighted large and small cubes which typically elicit expectation-based fingertip force errors. One group of participants observed the standard overestimation and underestimation-style errors that characterise early lifts with these cubes (Error video--EV). Another group watched the same actors performing the well-adapted error-free lifts that characterise later, well-practiced lifts with these cubes (No error video--NEV). We then examined actual object lifting performance in the subjects who watched the EV and NEV. Despite having similar cognitive expectations and perceptions of heaviness, the group that watched novice lifters making errors themselves made fewer overestimation-style errors than those who watched the expert lifts. To determine how the observation of errors alters cortico-spinal excitability, we measured motor evoked potentials in separate group of participants while they passively observed these EV and NEV. Here, we noted a novel size-based modulation of cortico-spinal excitability when observing the expert lifts, which was eradicated when watching errors. Together, these findings suggest that individuals' sensorimotor systems are sensitive to the subtle visual differences between observing novice and expert performance.G. Buckingham was supported with a Banting Postdoctoral Fellowship, awarded by the Natural Sciences and Engineering Council of Canada (NSERC

Characterisation of the porous structure of Gilsocarbon graphite using pycnometry, cyclic porosimetry and void-network modeling

file: :C$$:/pdf/1-s2.0-S000862231400164X-main.pdf:pdfThe cores of the fourteen Advanced Gas-cooled nuclear Reactors (AGRs) within the UK comprise Gilsocarbon graphite, a manufactured material surrounded predominantly by CO2 at high pressure and temperature to provide heat exchange. The intense ionising radiation within the reactors causes radiolytic oxidation, and the resulting mass loss is a primary factor in determining reactor lifetime. The void structure of the porous Gilsocarbon graphite affects the permeability and diffusion of the carbon dioxide, and the sites of oxidation. To model this void structure, the porosities and densities of ten virgin Gilsocarbon graphite samples have been measured by powder and helium pycnometry. For comparison, results are also presented for highly ordered pyrolytic graphite (HOPG), and a fine-grained Ringsdorff graphite. Samples have been examined at a range of magnifications by electron microscopy. Total porosities and percolation characteristics have been measured by standard and cyclic mercury porosimetry up to an applied mercury pressure of 400MPa. Inverse modelling of the cyclic intrusion curves produces simulated void structures with characteristics which closely match those of experiment. Void size distributions of the structures are presented, together with much Supplementary Information. The simulated void networks provide the bases for future simulations of the radiolytic oxidation process itself

The contributions of maternal age heterogeneity to variance in lifetime reproductive output

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in van Daalen, S. F., Hernandez, C. M., Caswell, H., Neubert, M. G., & Gribble, K. E. The contributions of maternal age heterogeneity to variance in lifetime reproductive output. American Naturalist,199(5), (2022): 603-616, https://doi.org/10.1086/718716.Variance among individuals in fitness components reflects both genuine heterogeneity between individuals and stochasticity in events experienced along the life cycle. Maternal age represents a form of heterogeneity that affects both the mean and the variance of lifetime reproductive output (LRO). Here, we quantify the relative contribution of maternal age heterogeneity to the variance in LRO using individual-level laboratory data on the rotifer Brachionus manjavacas to parameterize a multistate age × maternal age matrix model. In B. manjavacas, advanced maternal age has large negative effects on offspring survival and fertility. We used multistate Markov chains with rewards to quantify the contributions to variance in LRO of heterogeneity and of the stochasticity inherent in the outcomes of probabilistic transitions and reproductive events. Under laboratory conditions, maternal age heterogeneity contributes 26% of the variance in LRO. The contribution changes when mortality and fertility are reduced to mimic more ecologically relevant environments. Over the parameter space where populations are near stationarity, maternal age heterogeneity contributes an average of 3% of the variance. Thus, the contributions of maternal age heterogeneity and individual stochasticity can be expected to depend strongly on environmental conditions; over most of the parameter space, the variance in LRO is dominated by stochasticity.K.E.G. was supported by grant 5K01AG049049 from the National Institute on Aging, by National Science Foundation (NSF) CAREER grant IOS-1942606, and by the Bay and Paul Foundations. H.C. and S.F.v.D. were supported by the European Research Council through Advanced Grants 322829 and 788195 and by the Dutch Research Council through grant ALWOP.2015.100. S.F.v.D. was furthermore supported by the Postdoctoral Scholar Program at Woods Hole Oceanographic Institution, with funding provided by the Doherty Foundation. C.M.H. was supported by an NSF Graduate Research Fellowship. M.G.N. received funding from the Paul MacDonald Fye Chair for Excellence in Oceanography at the Woods Hole Oceanographic Institution

Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients.

RATIONALE: Meal ingestion triggers secretion of a variety of gut and endocrine peptides important in diabetes research which are routinely measured by immunoassays. However, similarities between some peptides (glucagon, oxyntomodulin and glicentin) can cause specificity issues with immunoassays. We used a liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodology to unambiguously monitor multiple gut peptides in human plasma. METHODS: A simple acetonitrile-based protein precipitation step, followed by evaporation and solid-phase extraction, removed high-abundance proteins from samples prior to nano-LC/MS/MS analysis on an Orbitrap Q-Exactive Plus mass spectrometer using a data-dependent methodology. Database searching using PEAKS identified multiple gut-derived peptides, including peptides in the mid-pg/mL range. The relative levels of these and previously characterised peptides were assessed in plasma samples from gastrectomised and control subjects during an oral glucose tolerance test. RESULTS: Analysis of plasma extracts revealed significantly elevated levels of a number of peptides following glucose ingestion in subjects who had undergone gastrectomy compared with controls. These included GLP-1(7-36), GLP-1(9-36), glicentin, oxyntomodulin, GIP(1-42), GIP(3-42), PYY(1-36), PYY(3-36), neurotensin, insulin and C-peptide. Motilin levels decreased following glucose ingestion. Results showed good correlation with immunoassay-derived concentrations of some peptides in the same samples. The gastrectomy group also had higher, but non-glucose-dependent, circulating levels of peptides from PIGR and DMBT1. CONCLUSIONS: Overall, the approach showed that a fast, generic and reproducible LC/MS/MS methodology requiring only a small volume of plasma was capable of the multiplexed detection of a variety of diabetes-related peptides.Wellcome Trust and MR

Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells

Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli

Catalytic reductive N-alkylation of amines using carboxylic acids

We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction

Chronic Ankle Instability and Neural Excitability of the Lower Extremity

Neuromuscular dysfunction of the leg and thigh musculature, including decreased strength and postural control, is common in patients with chronic ankle instability (CAI). Understanding how CAI affects specific neural pathways may provide valuable information for targeted therapies

The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1.

To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes. Glucose-dependent insulinotropic peptide (GIP) was not detectable. High fat diet modestly increased islet content of proinsulin-derived peptides in mice. Human diabetic islets contained increased content of proglucagon-derived peptides at the expense of insulin, but no evident prohormone processing defects. Diabetic plasma, however, contained increased ratios of proinsulin and des-31,32-proinsulin to insulin. Active GLP-1 was detectable in human and mouse islets but 100-1000-fold less abundant than glucagon. LC-MS offers advantages over antibody-based approaches for identifying exact peptide sequences, and revealed a shift toward islet insulin production in high fat fed mice, and toward proglucagon production in type 2 diabetes, with no evidence of systematic defective prohormone processing

Organoid Sample Preparation and Extraction for LC-MS Peptidomics.

This protocol describes the peptidomic analysis of organoid lysates, FACS-purified cell populations, and 2D culture secretions by liquid chromatography mass spectrometry (LC-MS). Currently, most peptides are quantified by ELISA, limiting the peptides that can be studied. However, an LC-MS-based approach allows more peptides to be monitored. Our group has previously used LC-MS for tissue peptidomics and secretion of enteroendocrine peptides from primary culture. Now, we extend the use to organoid models. For complete details on the use and execution of this protocol, please refer to Goldspink et al. (2020)

The impact of clinical placements on the emotional intelligence of occupational therapy, physiotherapy, speech pathology, and business students: a longitudinal study

Background: Emotional intelligence (EI) is a critical skill for healthcare practitioners. Minimal longitudinal research has tracked the changes in EI of therapy students over their final full-time clinical placements. Methods: The Emotional Quotient Inventory (EQ-i2.0) measured the EI of 283 therapy students and 93 business students (control group who do no clinical placements) at three time points over a 16-month period, the same period that the therapy students participated in clinical placements. Results: Analysis of the therapy students showed significant increases over the 16 months of the study in Total EI score, as well as nine other EI skills. However, large percentages of students reported declining scores in emotional expression, assertiveness, self-expression, and stress tolerance, with some students reporting low EI scores before commencing full-time extended clinical placements. Conclusions: The study contributes to new knowledge about the changing EI skills of therapy students as they complete their full-time, extended placements. Emotional intelligence in student therapists should be actively fostered during coursework, clinical placements and when first entering the workforce. University educators are encouraged to include EI content through the therapy curricula. Employers are encouraged to provide peer coaching, mentoring and workshops focused on EI skills to recent graduates