Multiscale modelling of plant hormone signalling: auxin regulated lateral root emergence

The formation of lateral roots is an important post-embryonic developmental process that allows plants to adapt to their environment via exploitation of soil mineral resources. New lateral roots initiate as lateral root primordia (LRP) in the pericycle cell layer adjacent to the central vascular tissue in the primary root, and must pass through the outer cell layers of endodermis, cortex and epidermis to emerge as mature roots. A key regulator of emergence is the plant hormone auxin and it has been shown previously that in Arabidopsis the auxin induced expression of the auxin influx carrier LAX3 in specific cortical cells over LRP is required for emergence to occur, as this leads to the expression of cell wall remodelling enzymes such as polygalacturonase (PG). By developing mathematical models of auxin transport and LAX3 expression the work in the thesis aims to test the existing conceptual models for lateral root emergence, and provide testable hypotheses for the existence of additional gene regulatory components. An initial single cell model demonstrates that hysteresis and bistability may explain the experimentally observed `all-or-nothing' LAX3 spatial expression pattern in cortical cells containing a gradient of auxin concentrations. By fitting model parameters against experimental data, the model is then used to show that some auxin homeostasis mechanism is present, with both endogenous and exogenous sources of homeostasis investigated. The single cell model also investigates the validity of several alternative gene regulatory networks for LAX3, and its apparent repression by a key mediator of the auxin response, ARF19. Finally, the model is extended to a multicellular context, in which the auxin distribution from a simulated LRP source cell is used as a basis for the expression of LAX3, leading to the expression of PG in specific cells between which the LRP must pass

Multiscale modelling of plant hormone signalling: auxin regulated lateral root emergence

The formation of lateral roots is an important post-embryonic developmental process that allows plants to adapt to their environment via exploitation of soil mineral resources. New lateral roots initiate as lateral root primordia (LRP) in the pericycle cell layer adjacent to the central vascular tissue in the primary root, and must pass through the outer cell layers of endodermis, cortex and epidermis to emerge as mature roots. A key regulator of emergence is the plant hormone auxin and it has been shown previously that in Arabidopsis the auxin induced expression of the auxin influx carrier LAX3 in specific cortical cells over LRP is required for emergence to occur, as this leads to the expression of cell wall remodelling enzymes such as polygalacturonase (PG). By developing mathematical models of auxin transport and LAX3 expression the work in the thesis aims to test the existing conceptual models for lateral root emergence, and provide testable hypotheses for the existence of additional gene regulatory components. An initial single cell model demonstrates that hysteresis and bistability may explain the experimentally observed `all-or-nothing' LAX3 spatial expression pattern in cortical cells containing a gradient of auxin concentrations. By fitting model parameters against experimental data, the model is then used to show that some auxin homeostasis mechanism is present, with both endogenous and exogenous sources of homeostasis investigated. The single cell model also investigates the validity of several alternative gene regulatory networks for LAX3, and its apparent repression by a key mediator of the auxin response, ARF19. Finally, the model is extended to a multicellular context, in which the auxin distribution from a simulated LRP source cell is used as a basis for the expression of LAX3, leading to the expression of PG in specific cells between which the LRP must pass

Auxin fluxes through plasmodesmata modify root-tip auxin distribution

© 2020. Published by The Company of Biologists Ltd. Auxin is a key signal regulating plant growth and development. It is well established that auxin dynamics depend on the spatial distribution of efflux and influx carriers on the cell membranes. In this study, we employ a systems approach to characterise an alternative symplastic pathway for auxin mobilisation via plasmodesmata, which function as intercellular pores linking the cytoplasm of adjacent cells. To investigate the role of plasmodesmata in auxin patterning, we developed a multicellular model of the Arabidopsis root tip. We tested the model predictions using the DII-VENUS auxin response reporter, comparing the predicted and observed DII-VENUS distributions using genetic and chemical perturbations designed to affect both carrier-mediated and plasmodesmatal auxin fluxes. The model revealed that carrier-mediated transport alone cannot explain the experimentally determined auxin distribution in the root tip. In contrast, a composite model that incorporates both carrier-mediated and plasmodesmatal auxin fluxes re-capitulates the root-tip auxin distribution. We found that auxin fluxes through plasmodesmata enable auxin reflux and increase total root-tip auxin. We conclude that auxin fluxes through plasmodesmata modify the auxin distribution created by efflux and influx carriers

Dynamic regulation of AtDAO1 and GH3 modulates auxin homeostasis

The hormone auxin is a key regulator of plant growth and development, and great progress has been made understanding auxin transport and signaling. Here we show that auxin metabolism and homeostasis are also regulated in a complex manner. The principal auxin degradation pathways in Arabidopsis include oxidation by AtDAO1/2 and conjugation by GH3s. Metabolic profiling of dao1-1 root tissues revealed a 50% decrease in the oxidation product oxIAA, an increase in the conjugated forms IAA-Asp and IAA-Glu of 438-fold and 240-fold respectively, while auxin remains close to wild type. By fitting parameter values to a mathematical model of these metabolic pathways we show that, in addition to reduced oxidation, both auxin biosynthesis and conjugation are increased in dao1-1. We then quantified gene expression in plantae, and found that transcripts of AtDAO1 and GH3 genes are increased in response to auxin, over different time scales and concentration ranges. Including this regulation of AtDAO1 and GH3 in an extended model reveals that auxin oxidation is more important for auxin homoeostasis at lower hormone concentrations, while auxin conjugation is most significant at high auxin levels. Finally, embedding our homeostasis model in a multicellular simulation to assess the spatial effect of the dao1-1 mutant shows that auxin increases in outer root tissues, in agreement with the dao1-1 mutant root hair phenotype. We conclude that auxin homeostasis is dependent on AtDAO1, acting in concert with GH3, to maintain auxin at optimal levels for plant growth and development

Lattice-matched epitaxial graphene grown on boron nitride

Lattice-matched graphene on hexagonal boron nitride is expected to lead to the formation of a band-gap but requires the formation of highly strained material and has not hitherto been realised. We demonstrate that aligned, lattice-matched graphene can be grown by molecular beam epitaxy using substrate temperatures in the range 1600-1710 °C and co-exists with a topologically-modified moiré pattern, and with regions of strained graphene which have giant moiré periods up to ~80 nm. Raman spectra reveal narrow red-shifted peaks due to isotropic strain, while the giant moiré patterns result in complex splitting of Raman peaks due to strain variations across the moiré unit cell. The lattice-matched graphene has a lower conductance than both the Frenkel-Kontorova-type domain walls, and also the topological defects where they terminate. We relate these results to theoretical models of band-gap formation in graphene/boron nitride heterostructures

Systems approaches reveal that ABCB and PIN proteins mediate co-dependent auxin efflux

Members of the B family of membrane-bound ATP-binding cassette (ABC) transporters represent key components of the auxin-efflux machinery in plants. Over the last two decades experimental studies have shown that modifying ABCB expression affects auxin distribution and plant phenotypes. However, precisely how ABCB proteins transport auxin in conjunction with the more widely studied family of PIN-formed (PIN) auxin efflux transporters is unclear, and studies using heterologous systems have produced conflicting results.Here, we integrate ABCB localization data into a multicellular model of auxin transport in the Arabidopsis thaliana root tip to predict how ABCB-mediated auxin transport impacts organ-scale auxin distribution. We use our model to test five potential ABCB–PIN regulatory interactions, simulating the auxin dynamics for each interaction and quantitatively comparing the predictions with experimental images of the DII-VENUS auxin reporter in wild type and abcb single and double loss-of-function mutants. Only specific ABCB–PIN regulatory interactions result in predictions that recreate the experimentally observed DII-VENUS distributions and long-distance auxin transport. Our results suggest that ABCBs enable auxin efflux independently of PINs; however, PIN-mediated auxin efflux is predominantly through a co-dependent efflux where co-localised with ABCBs

The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels:a Systematic Review

The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200–400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions

Managing health professional migration from sub-Saharan Africa to Canada: a stakeholder inquiry into policy options

BACKGROUND: Canada is a major recipient of foreign-trained health professionals, notably physicians from South Africa and other sub-Saharan African countries. Nurse migration from these countries, while comparatively small, is rising. African countries, meanwhile, have a critical shortage of professionals and a disproportionate burden of disease. What policy options could Canada pursue that balanced the right to health of Africans losing their health workers with the right of these workers to seek migration to countries such as Canada? METHODS: We interviewed a small sample of émigré South African physicians (n = 7) and a larger purposive sample of representatives of Canadian federal, provincial, regional and health professional departments/organizations (n = 25); conducted a policy colloquium with stakeholder organizations (n = 21); and undertook new analyses of secondary data to determine recent trends in health human resource flows between sub-Saharan Africa and Canada. RESULTS: Flows from sub-Saharan Africa to Canada have increased since the early 1990s, although they may now have peaked for physicians from South Africa. Reasons given for this flow are consistent with other studies of push/pull factors. Of 8 different policy options presented to study participants, only one received unanimous strong support (increasing domestic self-sufficiency), one other received strong support (increased health system strengthening in source country), two others mixed support (voluntary codes on ethical recruitment, bilateral or multilateral agreements to manage flows) and four others little support or complete rejection (increased training of auxiliary health workers in Africa ineligible for licensing in Canada, bonding, reparation payments for training-cost losses and restrictions on immigration of health professionals from critically underserved countries). CONCLUSION: Reducing pull factors by improving domestic supply and reducing push factors by strengthening source country health systems have the greatest policy traction in Canada. The latter, however, is not perceived as presently high on Canadian stakeholder organizations' policy agendas, although support for it could grow if it is promoted. Canada is not seen as "actively' recruiting" ("poaching") health workers from developing countries. Recent changes in immigration policy, ongoing advertising in southern African journals and promotion of migration by private agencies, however, blurs the distinction between active and passive recruitment

Social cohesion through football: a quasi-experimental mixed methods design to evaluate a complex health promotion program

Social isolation and disengagement fragments local communities. Evidence indicates that refugee families are highly vulnerable to social isolation in their countries of resettlement. Research to identify approaches to best address this is needed. Football United is a program that aims to foster social inclusion and cohesion in areas with high refugee settlement in New South Wales, Australia, through skills and leadership development, mentoring, and the creation of links with local community and corporate leaders and organisations. The Social Cohesion through Football study’s broad goal is to examine the implementation of a complex health promotion program, and to analyse the processes involved in program implementation. The study will consider program impact on individual health and wellbeing, social inclusion and cohesion, as well as analyse how the program by necessity interacts and adapts to context during implementation, a concept we refer to as plasticity. The proposed study will be the first prospective cohort impact study to our knowledge to assess the impact of a comprehensive integrated program using football as a vehicle for fostering social inclusion and cohesion in communities with high refugee settlement

McTaggart's paradox and Smith's tensed theory of time

Since McTaggart first proposed his paradox asserting the unreality of time, numerous philosophers have attempted to defend the tensed theory of time against it. Certainly, one of the most highly developed and original is that put forth by Quentin Smith. Through discussing McTaggart's positive conception of time as well as his negative attack on its reality, I hope to clarify the dispute between those who believe in the existence of the transitory temporal properties of pastness, presentness and futurity , and those who deny their existence. We shall see that the debate centers around the ontological status of succession and the B-relations of earlier and later . I shall argue that Smith's tensed theory fails because he cannot account for the sense in which events have their tensed properties successively, and he cannot account for the direction of time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43817/1/11229_2004_Article_BF00413606.pd