Network organisation and the dynamics of tubules in the endoplasmic reticulum

From Springer Nature via Jisc Publications RouterHistory: received 2021-04-26, accepted 2021-06-27, registration 2021-07-19, pub-electronic 2021-08-10, online 2021-08-10, collection 2021-12Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/H017828/1Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100010269; Grant(s): 215189/Z/19/ZFunder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266Abstract: The endoplasmic reticulum (ER) is a eukaryotic subcellular organelle composed of tubules and sheet-like areas of membrane connected at junctions. The tubule network is highly dynamic and undergoes rapid and continual rearrangement. There are currently few tools to evaluate network organisation and dynamics. We quantified ER network organisation in Vero and MRC5 cells, and developed an analysis workflow for dynamics of established tubules in live cells. The persistence length, tubule length, junction coordination number and angles of the network were quantified. Hallmarks of imbalances in ER tension, indications of interactions with microtubules and other subcellular organelles, and active dynamics were observed. Clear differences in dynamic behaviour were observed for established tubules at different positions within the cell using itemset mining. We found that tubules with activity-driven fluctuations were more likely to be located away from the cell periphery and a population of peripheral tubules with no signs of active motion was found

Short-Term Medical Costs of a VHA Health Information Exchange: A CHEERS-Compliant Article.

The Virtual Lifetime Electronic Record (VLER) Health program provides the Veterans Health Administration (VHA) a framework whereby VHA providers can access the veterans’ electronic health record information to coordinate healthcare across multiple sites of care. As an early adopter of VLER, the Indianapolis VHA and Regenstrief Institute implemented a regional demonstration program involving bi-directional health information exchange (HIE) between VHA and non-VHA providers.The aim of the study is to determine whether implementation of VLER HIE reduces 1 year VHA medical costs.A cohort evaluation with a concurrent control group compared VHA healthcare costs using propensity score adjustment. A CHEERs compliant checklist was used to conduct the cost evaluation.Patients were enrolled in the VLER program onsite at the Indianapolis VHA in outpatient clinics or through the release-of-information office.VHA cost data (in 2014 dollars) were obtained for both enrolled and nonenrolled (control) patients for 1 year prior to, and 1 year after, the index date of patient enrollment.There were 6104 patients enrolled in VLER and 45,700 patients in the control group. The annual adjusted total cost difference per patient was associated with a higher cost for VLER enrollees $1152 (95$807–1433) (P < 0.01) (in 2014 dollars) than VLER nonenrollees.Short-term evaluation of this demonstration project did not show immediate reductions in healthcare cost as might be expected if HIE decreased redundant medical tests and treatments. Cost reductions from shared health information may be realized with longer time horizons

Vocal Cord Dysfunction Etiologies and Treatment

Abstract: Vocal cord dysfunction, a syndrome of paradoxical inspiratory closure of the vocal cords, is becoming more frequently recognized and diagnosed recently since its initial modern description 30 years ago. Initially described as single case reports, the first case series in 1983 helped to clarify the typical patient and findings of vocal cord dysfunction. Recent investigations have elucidated specific etiologies such as gastroesophageal reflux, exercise, and irritants as causative factors in addition to the numerous associated psychologic factors. Speech therapy and psychotherapy have been used extensively with vocal cord dysfunction patients, but the optimal treatment has yet to be prospectively studied. This manuscript provides a comprehensive review of the reported causative factors and treatments for vocal cord dysfunction

Ice nucleation by particles containing long-chain fatty acids of relevance to freezing by sea spray aerosols.

Heterogeneous ice nucleation in the atmosphere regulates cloud properties, such as phase (ice versus liquid) and lifetime. Aerosol particles of marine origin are relevant ice nucleating particle sources when marine aerosol layers are lifted over mountainous terrain and in higher latitude ocean boundary layers, distant from terrestrial aerosol sources. Among many particle compositions associated with ice nucleation by sea spray aerosols are highly saturated fatty acids. Previous studies have not demonstrated their ability to freeze dilute water droplets. This study investigates ice nucleation by monolayers at the surface of supercooled droplets and as crystalline particles at temperatures exceeding the threshold for homogeneous freezing. Results show the poor efficiency of long chain fatty acid (C16, C18) monolayers in templating freezing of pure water droplets and seawater subphase to temperatures of at least -30 °C, consistent with theory. This contrasts with freezing of fatty alcohols (C22 used here) at nearly 20 °C warmer. Evaporation of μL-sized droplets to promote structural compression of a C19 acid monolayer did not favor warmer ice formation of drops. Heterogeneous ice nucleation occurred for nL-sized droplets condensed on 5 to 100 μm crystalline particles of fatty acid (C12 to C20) at a range of temperatures below -28 °C. These experiments suggest that fatty acids nucleate ice at warmer than -36 °C only when the crystalline phase is present. Rough estimates of ice active site densities are consistent with those of marine aerosols, but require knowledge of the proportion of surface area comprised of fatty acids for application

In vitro and preclinical assessment of an intranasal spray formulation of parathyroid hormone PTH 1-34 for the treatment of osteoporosis

Osteoporosis treatment with PTH 1-34 injections significantly reduces the incidence of bone fracture. Potential further reductions in fracture rate should be observed through nasal spray delivery to address the poor compliance associated with patient dislike of repeated PTH 1-34 subcutaneous injections. In vitro human osteoblast-like Saos-2 cell intracellular cAMP levels were used to define PTH 1-34 nasal spray formulation bioactivity. The chemically synthesised PTH 1-34 had an EC50 of 0.76nM. Absorption enhancers polyethylene glycol (15)-hydroxystearate (Solutol® HS15), poloxamer 407, chitosan or sodium hyaluronate did not diminish the bioactivity of PTH 1-34 within an in vitro cell culture model (p>0.05). We also demonstrated the effectiveness of the transmucosal absorption enhancer Solutol® HS15 in a nasal spray formulation using a preclinical pharmacokinetic model. In Sprague-Dawley rats without the absorption enhancer the uptake of PTH 1-34 into the blood via intranasal delivery produced a Cmax of 2.1±0.5 ng/ml compared to 13.7±1.6 ng/ml with Solutol® HS15 enhancer (p=0.016) and a Cmax14.8±8 ng/ml in subcutaneous injections. Together these data illustrate that the nasal spray formulation bioactivity in vitro is not affected by the nasal spray absorption enhancers investigated, and the Solutol® HS15 nasal spray formulation had an equivalent pharmacokinetic profile to subcutaneous injection in the rat model. The Solutol® HS15 formulation therefore demonstrated potential as a PTH 1-34 nasal spray formulation for the treatment of osteoporosis

Relationship of a big five personality questionnaire to the symptoms of affective disorders

Online assessments allow cost-effective, large-scale screening for psychiatric vulnerability (e.g., university undergraduates or military recruits). However, conventional psychiatric questionnaires may worsen mental health outcomes due to overmedicalizing normal emotional reactions. Personality questionnaires designed for occupational applications could circumvent this problem as they utilise non-clinical wording and it is well-established that personality traits influence susceptibility to psychiatric illness. Here we present a brief, free-to-use occupational personality questionnaire, and test its sensitivity to symptoms of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in an online sample. Our study used a cross-sectional, self-report design to assess the relationship between self-reported symptoms of affective disorders and scores on the personality dimensions of openness, conscientiousness, extraversion, agreeableness and neuroticism. We used SEM to compare affective symptoms in 8,470 individuals (mean age 25.6 ± 7.0 years; 4,717 male) with scores on an online adaption of the TSDI, a public-domain ‘Big Five’ personality questionnaire. ROC curve analyses assessed cut off scores for the best predictors of overall vulnerability to affective disorders (represented by a composite screening score). Neuroticism was the most robust predictor of QIDS-16 depression symptoms and MDQ Hypomania symptoms (β = 0.68 and 0.39 respectively, p < .0001). Extraversion was the most robust predictor of HCL-16 Hypomania symptoms (β = 0.34, p < .0001). ROC curve analyses suggest if the TSDI was used for screening in this sample, neuroticism cut offs of approximately 58 for men and 70 for women would provide the most useful classification of overall vulnerability to affective disorders

Sacred Cows and Sympathetic Squirrels: The Importance of Biological Diversity to Human Health

Dobson and colleagues describe how some host species act to reduce the risk of transmission of virulent zoonotic pathogens to humans

What can cetacean stranding records tell us? A study of UK and Irish cetacean diversity over the past 100 years

There are many factors that may explain why cetaceans (whales, dolphins, and porpoises) strand. Around the UK and Ireland, over 20,000 stranding records have been collected since 1913, resulting in one of the longest, continuous, systematic stranding data sets in the world. We use this data set to investigate temporal and spatial trends in cetacean strandings and use generalized additive models (GAMs) to investigate correlates of strandings. We find a dramatic increase in strandings since the 1980s, most likely due to increases in recording effort, and the formation of formal strandings networks. We found no correlation between the numbers of cetaceans stranding each year and several potential environmental and anthropogenic predictors: storms, geomagnetic activity, North Atlantic Oscillations, sea‐surface temperature, and fishing catch. We suggest that this is because the scale of change in the variables is too coarse to detect any potential correlations. It may also highlight the idiosyncratic nature of species’ responses to external pressures, and further the need to investigate other potential correlates of strandings, such as bycatch and military sonar. Long‐term cetacean stranding data provide vital information on past and present diversity for common, rare, and inconspicuous species. This study underlines the importance of continued support for stranding networks.This is the peer reviewed version of the following article: Coombs, E.J., Deaville, R., Sabin, R.C., Allan, L., O'Connell, M., Berrow, S., Smith, B., Brownlow, A., Doeschate, M.T., Penrose, R., Williams, R., Perkins, M.W., Jepson, P.D. and Cooper, N. (2019), What can cetacean stranding records tell us? A study of UK and Irish cetacean diversity over the past 100 years. Mar Mam Sci, 35: 1527-1555. , which has been published in final form at doi:10.1111/mms.12610. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Mosaic fungal individuals have the potential to evolve within a single generation

Although cells of mushroom-producing fungi typically contain paired haploid nuclei (n + n), most Armillaria gallica vegetative cells are uninucleate. As vegetative nuclei are produced by fusions of paired haploid nuclei, they are thought to be diploid (2n). Here we report finding haploid vegetative nuclei in A. gallica at multiple sites in southeastern Massachusetts, USA. Sequencing multiple clones of a single-copy gene isolated from single hyphal filaments revealed nuclear heterogeneity both among and within hyphae. Cytoplasmic bridges connected hyphae in field-collected and cultured samples, and we propose nuclear migration through bridges maintains this nuclear heterogeneity. Growth studies demonstrate among- and within-hypha phenotypic variation for growth in response to gallic acid, a plant-produced antifungal compound. The existence of both genetic and phenotypic variation within vegetative hyphae suggests that fungal individuals have the potential to evolve within a single generation in response to environmental variation over time and space