Effects of diamagnetic levitation on bacterial growth in liquid

Diamagnetic levitation is a technique that uses a strong, spatially-varying magnetic field to levitate diamagnetic materials, such as water and biological cells. This technique has the potential to simulate aspects of weightlessness, on the Earth. In common with all ground-based techniques to simulate weightlessness, however, there are effects introduced by diamagnetic levitation that are not present in space. Since there have been few studies that systematically investigate these differences, diamagnetic levitation is not yet being fully exploited. For the first time, we critically assess the effect of diamagnetic levitation on a bacterial culture in liquid. We used a superconducting magnet to levitate growing bacterial cultures for up to 18 hours, in a series of experiments to determine the effect of diamagnetic levitation on all phases of the bacterial growth cycle. We find that diamagnetic levitation increases the rate of population growth in a liquid culture. The speed of sedimentation of the bacterial cells to the bottom of the container is considerably reduced. Further experiments and microarray gene analysis show that the growth enhancement is due to greater oxygen availability in the magnetically levitated sample. We demonstrate that the magnetic field that levitates the cells also induces convective stirring in the liquid, an effect not present in microgravity. We present a simple theoretical model, showing how the paramagnetic force on dissolved oxygen can cause the liquid to become unstable to convection when the consumption of oxygen by the bacteria generates an oxygen concentration gradient. We propose that this convection enhances oxygen availability by transporting oxygen around the sample. Since convection is absent in space, these results are of significant importance and timeliness to researchers considering using diamagnetic levitation to explore weightless effects on living organisms and a broad range of other topics in the physical and life sciences

A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia

Schizophrenia shows a genetic correlation with both anxiety disorder and neuroticism, a trait strongly associated with anxiety. However, genetic correlations do not discern causality from genetic confounding. We therefore aimed to investigate whether anxiety-related phenotypes lie on the causal pathway to schizophrenia using Mendelian randomization (MR). Four MR methods, each with different assumptions regarding instrument validity, were used to investigate casual associations of anxiety and neuroticism related phenotypes on schizophrenia, and vice versa: inverse variance weighted (IVW), weighted median, weighted mode, and, when appropriate, MR Egger regression. MR provided evidence of a causal effect of neuroticism on schizophrenia (IVW odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.12-1.59), but only weak evidence of a causal effect of anxiety on schizophrenia (IVW OR: 1.10, 95% CI: 1.01-1.19). There was also evidence of a causal association from schizophrenia liability to anxiety disorder (IVW OR: 1.28, 95% CI: 1.18-1.39) and worry (IVW beta: 0.05, 95% CI: 0.03-0.07), but effect estimates from schizophrenia to neuroticism were inconsistent in the main analysis. The evidence of neuroticism increasing schizophrenia risk provided by our results supports future efforts to evaluate neuroticism- or anxiety-based therapies to prevent onset of psychotic disorders

Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>Many biological systems respond to the presence or absence of gravity. Since experiments performed in space are expensive and can only be undertaken infrequently, Earth-based simulation techniques are used to investigate the biological response to weightlessness. A high gradient magnetic field can be used to levitate a biological organism so that its net weight is zero.</p> <p>Results</p> <p>We have used a superconducting magnet to assess the effect of diamagnetic levitation on the fruit fly <it>D. melanogaster </it>in levitation experiments that proceeded for up to 22 consecutive days. We have compared the results with those of similar experiments performed in another paradigm for microgravity simulation, the Random Positioning Machine (RPM). We observed a delay in the development of the fruit flies from embryo to adult. Microarray analysis indicated changes in overall gene expression of imagoes that developed from larvae under diamagnetic levitation, and also under simulated hypergravity conditions. Significant changes were observed in the expression of immune-, stress-, and temperature-response genes. For example, several heat shock proteins were affected. We also found that a strong magnetic field, of 16.5 Tesla, had a significant effect on the expression of these genes, independent of the effects associated with magnetically-induced levitation and hypergravity.</p> <p>Conclusions</p> <p>Diamagnetic levitation can be used to simulate an altered effective gravity environment in which gene expression is tuned differentially in diverse <it>Drosophila melanogaster </it>populations including those of different age and gender. Exposure to the magnetic field <it>per se </it>induced similar, but weaker, changes in gene expression.</p

Realizability of Polytopes as a Low Rank Matrix Completion Problem

This article gives necessary and sufficient conditions for a relation to be the containment relation between the facets and vertices of a polytope. Also given here, are a set of matrices parameterizing the linear moduli space and another set parameterizing the projective moduli space of a combinatorial polytope

PCSK9 genetic variants and cognitive abilities:a large-scale Mendelian randomization study

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Methods: We examined the association of genetic variants in PCSK9 with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in PCSK9 were used in up to 337,348 individuals. Results: The PCSK9 allele score was associated with a lower risk of CHD, and weakly with worse log reaction time. Conclusions: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising the potential need for continued pharmacovigilance for patients currently treated with PCSK9 inhibitors

Separating the direct effects of traits on atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

AIMS/HYPOTHESIS: Type 2 diabetes and atherosclerotic CVD share many risk factors. This study aimed to systematically assess a broad range of continuous traits to separate their direct effects on coronary and peripheral artery disease from those mediated by type 2 diabetes. METHODS: Our main analysis was a two-step Mendelian randomisation for mediation to quantify the extent to which the associations observed between continuous traits and liability to atherosclerotic CVD were mediated by liability to type 2 diabetes. To support this analysis, we performed several univariate Mendelian randomisation analyses to examine the associations between our continuous traits, liability to type 2 diabetes and liability to atherosclerotic CVD. RESULTS: Eight traits were eligible for the two-step Mendelian randomisation with liability to coronary artery disease as the outcome and we found similar direct and total effects in most cases. Exceptions included fasting insulin and hip circumference where the proportion mediated by liability to type 2 diabetes was estimated as 56% and 52%, respectively. Six traits were eligible for the analysis with liability to peripheral artery disease as the outcome. Again, we found limited evidence to support mediation by liability to type 2 diabetes for all traits apart from fasting insulin (proportion mediated: 70%). CONCLUSIONS/INTERPRETATION: Most traits were found to affect liability to atherosclerotic CVD independently of their relationship with liability to type 2 diabetes. These traits are therefore important for understanding atherosclerotic CVD risk regardless of an individual’s liability to type 2 diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00125-022-05653-1

Meristematic cell proliferation and ribosome biogenesis are decoupled in diamagnetically levitated Arabidopsis seedlings

Background: Cell growth and cell proliferation are intimately linked in the presence of Earth’s gravity, but are decoupled under the microgravity conditions present in orbiting spacecraft. New technologies to simulate microgravity conditions for long-duration experiments, with stable environmental conditions, in Earth-based laboratories are required to further our understanding of the effect of extraterrestrial conditions on the growth, development and health of living matter. Results: We studied the response of transgenic seedlings of Arabidopsis thaliana, containing either the CycB1-GUS proliferation marker or the DR5-GUS auxin-mediated growth marker, to diamagnetic levitation in the bore of a superconducting solenoid magnet. As a control, a second set of seedlings were exposed to a strong magnetic field, but not to levitation forces. A third set was exposed to a strong field and simulated hypergravity (2 g). Cell proliferation and cell growth cytological parameters were measured for each set of seedlings. Nucleolin immunodetection was used as a marker of cell growth. Collectively, the data indicate that these two fundamental cellular processes are decoupled in root meristems, as in microgravity: cell proliferation was enhanced whereas cell growth markers were depleted. These results also demonstrated delocalisation of auxin signalling in the root tip despite the fact that levitation of the seedling as a whole does not prevent the sedimentation of statoliths in the root cells. Conclusions:In our model system, we found that diamagnetic levitation led to changes that are very similar to those caused by real- [e.g. on board the International Space Station (ISS)] or mechanically-simulated microgravity [e.g. using a Random Positioning Machine (RPM)]. These changes decoupled meristematic cell proliferation from ribosome biogenesis, and altered auxin polar transport

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity