Rhizobial secretion of truncated exopolysaccharides severely impairs the Mesorhizobium-Lotus symbiosis.

The symbiosis between Mesorhizobium japonicum R7A and Lotus japonicus Gifu is an important model system for investigating the role of bacterial exopolysaccharides (EPS) in plant-microbe interactions. Previously we showed that R7A exoB mutants that are affected at an early stage of EPS synthesis and in lipopolysaccharide (LPS) synthesis induce effective nodules on L. japonicus Gifu after a delay, whereas exoU mutants affected in the biosynthesis of the EPS side chain induce small uninfected nodule primordia and are impaired in infection. The presence of a halo around the exoU mutant when grown on Calcofluor-containing media suggested the mutant secreted a truncated version of R7A EPS. A non-polar ΔexoA mutant defective in the addition of the first glucose residue to the EPS backbone was also severely impaired symbiotically. Here we used a suppressor screen to show that the severe symbiotic phenotype of the exoU mutant was due to secretion of an acetylated pentasaccharide, as both monomers and oligomers, by the same Wzx/Wzy system that transports wild-type exopolysaccharide. We also present evidence that the ΔexoA mutant secretes an oligosaccharide by the same transport system, contributing to its symbiotic phenotype. In contrast, ΔexoYF, and polar exoA and exoL mutants have a similar phenotype to exoB mutants, forming effective nodules after a delay. These studies provide substantial evidence that secreted incompatible EPS is perceived by the plant leading to abrogation of the infection process.

Rhizobium leguminosarum bv. trifolii NodD2 Enhances Competitive Nodule Colonization in the Clover-Rhizobium Symbiosis.

Establishment of the symbiotic relationship that develops between rhizobia and their legume hosts is contingent upon an interkingdom signal exchange. In response to host legume flavonoids, NodD proteins from compatible rhizobia activate expression of nodulation genes that produce lipochitin oligosaccharide signaling molecules known as Nod factors. Root nodule formation commences upon legume recognition of compatible Nod factor. Rhizobium leguminosarum was previously considered to contain one copy of nodD; here, we show that some strains of the Trifolium (clover) microsymbiont R. leguminosarum bv. trifolii contain a second copy designated nodD2. nodD2 genes were present in 8 out of 13 strains of R. leguminosarum bv. trifolii, but were absent from the genomes of 16 R. leguminosarum bv. viciae strains. Analysis of single and double nodD1 and nodD2 mutants in R. leguminosarum bv. trifolii strain TA1 revealed that NodD2 was functional and enhanced nodule colonization competitiveness. However, NodD1 showed significantly greater capacity to induce nod gene expression and infection thread formation. Clover species are either annual or perennial and this phenological distinction is rarely crossed by individual R. leguminosarum bv. trifolii microsymbionts for effective symbiosis. Of 13 strains with genome sequences available, 7 of the 8 effective microsymbionts of perennial hosts contained nodD2, whereas the 3 microsymbionts of annual hosts did not. We hypothesize that NodD2 inducer recognition differs from NodD1, and NodD2 functions to enhance competition and effective symbiosis, which may discriminate in favor of perennial hosts.IMPORTANCE Establishment of the rhizobium-legume symbiosis requires a highly specific and complex signal exchange between both participants. Rhizobia perceive legume flavonoid compounds through LysR-type NodD regulators. Often, rhizobia encode multiple copies of nodD, which is one determinant of host specificity. In some species of rhizobia, the presence of multiple copies of NodD extends their symbiotic host-range. Here, we identified and characterized a second copy of nodD present in some strains of the clover microsymbiont Rhizobium leguminosarum bv. trifolii. The second nodD gene contributed to the competitive ability of the strain on white clover, an important forage legume. A screen for strains containing nodD2 could be utilized as one criterion to select strains with enhanced competitive ability for use as inoculants for pasture production.

Intellectual disability and autism: socioeconomic impacts of informal caring, projected to 2030.

BACKGROUND: Intellectual disability and autism spectrum disorder (ASD) influence the interactions of a person with their environment and generate economic and socioeconomic costs for the person, their family and society. AIMS: To estimate costs of lost workforce participation due to informal caring for people with intellectual disability or autism spectrum disorders by estimating lost income to individuals, lost taxation payments to federal government and increased welfare payments. METHOD: We used a microsimulation model based on the Australian Bureau of Statistics' Surveys of Disability, Ageing and Carers (population surveys of people aged 15-64), and projected costs of caring from 2015 in 5-year intervals to 2030. RESULTS: The model estimated that informal carers of people with intellectual disability and/or ASD in Australia had aggregated lost income of AU$310 million, lost taxation of AU$100 million and increased welfare payments of AU$204 million in 2015. These are projected to increase to AU$432 million, AU$129 million and AU$254 million for income, taxation, and welfare respectively by 2030. The income gap of carers for people with intellectual disability and/or ASD is estimated to increase by 2030, meaning more financial stress for carers. CONCLUSIONS: Informal carers of people with intellectual disability and/or ASD experience significant loss of income, leading to increased welfare payments and reduced taxation revenue for governments; these are all projected to increase. Strategic policies supporting informal carers wishing to return to work could improve the financial and psychological impact of having a family member with intellectual disability and/or ASD. DECLARATION OF INTEREST: None.

Structures of Exopolysaccharides Involved in Receptor-mediated Perception of Mesorhizobium loti by Lotus japonicus.

In the symbiosis formed between Mesorhizobium loti strain R7A and Lotus japonicus Gifu, rhizobial exopolysaccharide (EPS) plays an important role in infection thread formation. Mutants of strain R7A affected in early exopolysaccharide biosynthetic steps form nitrogen-fixing nodules on L. japonicus Gifu after a delay, whereas mutants affected in mid or late biosynthetic steps induce uninfected nodule primordia. Recently, it was shown that a plant receptor-like kinase, EPR3, binds low molecular mass exopolysaccharide from strain R7A to regulate bacterial passage through the plant's epidermal cell layer (Kawaharada, Y., Kelly, S., Nielsen, M. W., Hjuler, C. T., Gysel, K., Muszynski, A., Carlson, R. W., Thygesen, M. B., Sandal, N., Asmussen, M. H., Vinther, M., Andersen, S. U., Krusell, L., Thirup, S., Jensen, K. J., et al. (2015) Nature 523, 308-312). In this work, we define the structure of both high and low molecular mass exopolysaccharide from R7A. The low molecular mass exopolysaccharide produced by R7A is a monomer unit of the acetylated octasaccharide with the structure (2,3/3-OAc)ß-d-RibfA-(1→4)-α-d-GlcpA-(1→4)-ß-d-Glcp-(1→6)-(3OAc)ß-d-Glcp-(1→6)-*[(2OAc)ß-d-Glcp-(1→4)-(2/3OAc)ß-d-Glcp-(1→4)-ß-d-Glcp-(1→3)-ß-d-Galp]. We propose it is a biosynthetic constituent of high molecular mass EPS polymer. Every new repeating unit is attached via its reducing-end ß-d-Galp to C-4 of the fourth glucose (asterisked above) of the octasaccharide, forming a branch. The O-acetylation occurs on the four glycosyl residues in a non-stoichiometric ratio, and each octasaccharide subunit is on average substituted with three O-acetyl groups. The availability of these structures will facilitate studies of EPR3 receptor binding of symbiotically compatible and incompatible EPS and the positive or negative consequences on infection by the M. loti exo mutants synthesizing such EPS variants.

Working Beyond the Traditional Retirement Age: The Influence of Health on Australia's Older Workers.

This article examines the relationship between health and workforce participation beyond the age of 65 years in Australia. This study found that people with a chronic health condition were less likely to be employed than those without a health condition (OR, 0.59; 95% CI [0.38, 0.92]). Among those with a chronic health condition, those in income quartile 2 (OR, 0.27; 95% CI [0.11, 0.67]) and 3 (OR, 0.38; 95% CI, [0.15-0.93]) were significantly less likely to be employed relative to those in income quartile 4. Older workers with a chronic health condition were less likely to work beyond the age of 65; however, among those with a chronic health condition, those with very high income and those with very low income were the most likely to keep working.

Labour force participation and the influence of having arthritis on financial status.

The objective of this study was to quantify the impact that having arthritis has on income poverty status and accumulated wealth in Australia. Cross-sectional analysis of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers and STINMOD, an income and savings microsimulation model. Across all categories of labour force participation status (employed full time, part time or not in the labour force at all), those with arthritis were significantly more likely to be in poverty. Those employed full time with no health condition had 0.82 times the odds of being in income poverty (95 % CI 0.80-0.84) compared with those employed full time with arthritis. Those not in the labour force with no chronic health conditions had 0.36 times the odds of being in income poverty compared with those not in the labour force due to arthritis (95 % CI 0.36-0.37). For people not in the labour force with no long-term health condition, the total value of their wealth was 211 % higher (95 % CI 38-618 %) than the amount of wealth accumulated by those not in the labour force due to arthritis. Similarly, those employed part time with no chronic health condition had 50 % more wealth than those employed part time with arthritis (95 % CI 3-116 %). Arthritis has a profound impact upon the economic circumstances of individuals, which adds a further dimension to the detrimental living standards of older individuals suffering from the condition.

Depression prevention, labour force participation and income of older working aged Australians: A microsimulation economic analysis.

OBJECTIVE: Depression has economic consequences not only for the health system, but also for individuals and society. This study aims to quantify the potential economic impact of five-yearly screening for sub-syndromal depression in general practice among Australians aged 45-64 years, followed by a group-based psychological intervention to prevent progression to depression. METHOD: We used an epidemiological simulation model to estimate reductions in prevalence of depression, and a microsimulation model, Health&WealthMOD2030, to estimate the impact on labour force participation, personal income, savings, taxation revenue and welfare expenditure. RESULTS: Group therapy is estimated to prevent around 5,200 prevalent cases of depression (2.2%) and add about 520 people to the labour force. Private incomes are projected to increase by $19 million per year, tax revenues by $2.4 million, and transfer payments are reduced by $2.6 million. CONCLUSION: Group-based psychological intervention to prevent depression could result in considerable economic benefits in addition to its clinical effects.

Multiple chronic health conditions and their link with wealth assets.

BACKGROUND: There has been little research on the economic status of those with multiple health conditions, particularly on the relationship between multiple health conditions and wealth. This paper will assess the difference in the value and type of wealth assets held by Australians who have multiple chronic health conditions. METHODS: Using Health&WealthMOD, a microsimulation model of the 45-64-year-old Australian population in 2009, a counterfactual analysis was undertaken. The actual proportion of people with different numbers of chronic health conditions with any wealth, and the value of this wealth was estimated. This was compared with the counterfactual values had the individuals had no chronic health conditions. RESULTS: There was no change in the proportion of people with one health condition who actually had any wealth, compared to the counterfactual proportion had they had no chronic health conditions. Ninety-four percent of those with four or more health conditions had some accumulated wealth; however, under the counterfactual, 100% would have had some accumulated wealth. There was little change in the value of non-income-producing assets under the counterfactual, regardless of number of health conditions. Those with four or more chronic health conditions had a mean value of $17 000 in income-producing assets; under the counterfactual, the average would have been $78 000. CONCLUSION: This study has highlighted the variation in the value of wealth according to number of chronic health conditions, and hence the importance of considering multiple morbidities when discussing the relationship between health and wealth.

Controlled mechnical modification of manganite surface with nanoscale resolution.

We investigated the surfaces of magnetoresistive manganites, La(1-x)Ca(x)MnO3 and La(2-2x)Sr(1+2x)Mn2O7, using a combination of ultrahigh vacuum conductive, electrostatic and magnetic force microscopy methods. Scanning as-grown film with a metal tip, even with zero applied bias, was found to modify the surface electronic properties such that in subsequent scans, the conductivity is reduced below the noise level of conductive probe microscopy. Scanned areas also reveal a reduced contact potential difference relative to the pristine surface by ∼0.3 eV. We propose that contact-pressure of the tip modifies the electrochemical potential of oxygen vacancies via the Vegard effect, causing vacancy motion and concomitant changes of the electronic properties.

Indirect economic impacts of comorbidities on people with heart disease.

BACKGROUND: Few studies have assessed the effect of multiple health conditions among patients with heart disease, particularly the economic implications of having multiple conditions. METHODS AND RESULTS: This study used a microsimulation model, Health&WealthMOD, to assess the effect of comorbidities on the labor force participation of 45-64-year-old Australians with heart disease, and the indirect economic costs to these individuals and government. For most comorbid conditions, there is a significant increase in the chance of an individual being out of the labor force, relative to those with heart disease alone. For example, individuals with heart disease and arthritis have more than 6-fold the odds of being out of the labor force relative to those with heart disease alone (OR 6.64, 95% CI: 2.46-17.95). People with heart disease and ≥1 comorbidities also receive a significantly lower income, pay less in taxation and receive more in government transfer payments than those with heart disease alone. CONCLUSIONS: It is important to consider whether an individual with heart disease also has other health conditions, as individuals with comorbidities have inferior financial situations and are a greater burden on government finances than those with only heart disease. (Circ J 2014; 78: 644-648).

How co-morbidities magnify the effect of arthritis on labour force participation and economic status: a costs of illness study in Australia.

Few studies have assessed the impact of co-morbid conditions amongst patients with arthritis. This study will quantify the impact co-morbid health conditions have on the labour force status and economic circumstances of people with arthritis. This study uses a microsimulation model, Health&WealthMOD, to quantify the impact of co-morbidities on the labour force participation and economic circumstances of 45- to 64-year-old Australians with arthritis. The results show that the probability of being out of the labour force increases with increasing number of co-morbidities. However, there was no statistically significant difference in the amount of weekly private income received by people with arthritis and no co-morbidities, and people with arthritis and one or two co-morbidities. However, those with arthritis and three or more co-morbidities received a weekly private income 72 % lower than people with arthritis alone (95 % CI -82, -57). People with arthritis and co-morbidities paid less in tax and received more in government transfer payments. As such, it is important to consider the co-morbid conditions an individual has when assessing the impact of arthritis on labour force participation and economic circumstances. People with arthritis that have multiple co-morbid conditions are likely to have their labour force participation and economic circumstances interrupted much more than those with arthritis only.

The economic impact of diabetes through lost labour force participation on individuals and government: evidence from a microsimulation model.

BACKGROUND: Diabetes is a costly and debilitating disease. The aim of the study is to quantify the individual and national costs of diabetes resulting from people retiring early because of this disease, including lost income; lost income taxation, increased government welfare payments; and reductions in GDP. METHODS: A purpose-built microsimulation model, Health&WealthMOD2030, was used to estimate the economic costs of early retirement due to diabetes. The study included all Australians aged 45-64 years in 2010 based on Australian Bureau of Statistics' Surveys of Disability, Ageing and Carers. A multiple regression model was used to identify significant differences in income, government welfare payments and taxation liabilities between people out of the labour force because of their diabetes and those employed full time with no chronic health condition. RESULTS: The median annual income of people who retired early because of their diabetes was significantly lower (AU$11,784) compared to those employed full time without a chronic health condition who received almost five times more income. At the national level, there was a loss of AU$384 million in individual earnings by those with diabetes, an extra AU$4 million spent in government welfare payments, a loss of AU$56 million in taxation revenue, and a loss of AU$1,324 million in GDP in 2010: all attributable to diabetes through its impact on labour force participation. Sensitivity analysis was used to assess the impact of different diabetes prevalence rates on estimates of lost income, lost income taxation, increased government welfare payments, and reduced GDP. CONCLUSIONS: Individuals bear the cost of lost income in addition to the burden of the disease. The Government endures the impacts of lost productivity and income taxation revenue, as well as spending more in welfare payments. These national costs are in addition to the Government's direct healthcare costs.

Mechanical control of electroresistive switching.

Hysteretic metal-insulator transitions (MIT) mediated by ionic dynamics or ferroic phase transitions underpin emergent applications for nonvolatile memories and logic devices. The vast majority of applications and studies have explored the MIT coupled to the electric field or temperarture. Here, we argue that MIT coupled to ionic dynamics should be controlled by mechanical stimuli, the behavior we refer to as the piezochemical effect. We verify this effect experimentally and demonstrate that it allows both studying materials physics and enabling novel data storage technologies with mechanical writing and current-based readout.

Economic impact of informal caring for a person with arthritis in Australia from 2015 to 2030: a microsimulation approach using national survey data.

OBJECTIVES: To estimate the economic burden of informal caregivers not in the labour force (NILF) due to caring for a person with arthritis in Australia, with projections of these costs from 2015 to 2030. DESIGN: Static microsimulation modelling using national survey data. SETTING: Australia nationwide survey. PARTICIPANTS: Participants include respondents to the Survey of Disability, Ageing and Carers who are informal carers of a person who has arthritis as their main chronic condition and non-carers. OUTCOME MEASURES: Estimating the economic impact and national aggregated costs of informal carers NILF to care for a person with arthritis and projecting these costs from 2015 to 2030 in 5-year intervals. RESULTS: On a per-person basis, when adjusted for age, sex and highest education attained, the difference in average weekly total income between informal carers and non-carers employed in the labour force is $A1051 (95% CI: $A927 to $A1204) in 2015 and projected to increase by up to 22% by 2030. When aggregated, the total national annual loss of income to informal carers NILF is estimated at $A388.2 million (95% CI: $A324.3 to $A461.9 million) in 2015, increasing to $A576.9 million (95% CI: $A489.2 to $A681.8 million) by 2030. The national annual tax revenue lost to the government of the informal carers NILF is estimated at $A99 million (95% CI: $A77.9 to $A126.4 million) in 2015 and is projected to increase 49% by 2030. CONCLUSION: Informal carers NILF are economically worse off than employed non-carers, and the aggregated national annual costs are substantial. The future economic impact of informal carers NILF to care for a person with arthritis in Australia is projected to increase, with the estimated differences in income between informal carers and employed non-carers increasing by 22% from 2015 to 2030.

Conditional requirement for exopolysaccharide in the Mesorhizobium-Lotus symbiosis.

Rhizobial surface polysaccharides are required for nodule formation on the roots of at least some legumes but the mechanisms by which they act are yet to be determined. As a first step to investigate the function of exopolysaccharide (EPS) in the formation of determinate nodules, we isolated Mesorhizobium loti mutants affected in various steps of EPS biosynthesis and characterized their symbiotic phenotypes on two Lotus spp. The wild-type M. loti R7A produced both high molecular weight EPS and lower molecular weight (LMW) polysaccharide fractions whereas most mutant strains produced only LMW fractions. Mutants affected in predicted early biosynthetic steps (e.g., exoB) formed nitrogen-fixing nodules on Lotus corniculatus and L. japonicus 'Gifu', whereas mutants affected in mid or late biosynthetic steps (e.g., exoU) induced uninfected nodule primordia and, occasionally, a few infected nodules following a lengthy delay. These mutants were disrupted at the stage of infection thread (IT) development. Symbiotically defective EPS and Nod factor mutants functionally complemented each other in co-inoculation experiments. The majority of full-length IT observed harbored only the EPS mutant strain and did not show bacterial release, whereas the nitrogen-fixing nodules contained both mutants. Examination of the symbiotic proficiency of the exoU mutant on various L. japonicus ecotypes revealed that both host and environmental factors were linked to the requirement for EPS. These results reveal a complex function for M. loti EPS in determinate nodule formation and suggest that EPS plays a signaling role at the stages of both IT initiation and bacterial release.

The personal and national costs of lost labour force participation due to arthritis: an economic study.

BACKGROUND: The costs of arthritis to the individuals and the state are considerable. METHODS: Cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model of 45 to 64 year old Australians built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers and STINMOD, an income and savings microsimulation model. RESULTS: Individuals aged 45 to 64 years who had retired early due to arthritis had a median value of AU$260 in total weekly income whereas those who were employed full time were likely to average more than five times this. The large national aggregate impact of early retirement due to arthritis includes AU$9.4 billion in lost GDP, attributable to arthritis through its impact on labour force participation.When looking at the ongoing impact of being out of the labour force those who retired from the labour force early due to arthritis were estimated to have a median value of total savings by the time they are 65 of as little as $300 (for males aged 45-54). This is far lower than the median value of savings for those males aged 45-54 who remained in the labour force full time, who would have an estimated $339,100 of savings at age 65. CONCLUSIONS: The costs of arthritis to the individuals and the state are considerable. The impacts on the state include loss of productivity from reduced workforce participation, lost income taxation revenue, and increased government support payments - in addition to direct health care costs. Individuals bear the economic costs of lost income and the reduction of their savings over the long term.

The association between labour force participation and being in income poverty amongst those with mental health problems.

OBJECTIVES: Mental health conditions are associated with lower standards of living. This study quantifies the relationship between employment, depression and other mental health conditions and being in income poverty. METHODS: Cross-sectional analysis was undertaken using the 2003 Survey of Disability, Ageing and Carers data for Australians aged 45-64 years. RESULTS: Those not in the labour force due to depression and other mental health conditions are significantly more likely (odds ratio (OR) 12.53, 95% CI: 12.20-12.86, p < 0.0001; OR 20.10, 95% CI: 19.67-20.54, p < 0.0001) to be in income poverty than those not in the labour force with no chronic health condition. Amongst those with depression and other mental health conditions, those who were in employment were significantly less likely to be in income poverty than those who have had to retire because of the condition. CONCLUSION: Due to the association between leaving the workforce due to mental health problems and poverty status, efforts to increase the employment of individuals with mental health conditions, or prevent the onset of the conditions, will likely improve living standards.

The impact of diabetes prevention on labour force participation and income of older Australians: an economic study.

BACKGROUND: Globally, diabetes is estimated to affect 246 million people and is increasing. In Australia diabetes has been made a national health priority. While the direct costs of treating diabetes are substantial, and rising, the indirect costs are considered greater. There is evidence that interventions to prevent diabetes are effective, and cost-effective, but the impact on labour force participation and income has not been assessed. In this study we quantify the potential impact of implementing a diabetes prevention program, using screening and either metformin or a lifestyle intervention on individual economic outcomes of pre-diabetic Australians aged 45-64. METHODS: The output of an epidemiological microsimulation model of the reduction in prevalence of diabetes from a lifestyle or metformin intervention, and another microsimulation model, Health&WealthMOD, of health and the associated impacts on labour force participation, personal income, savings, government revenue and expenditure were used to quantify the estimated outcomes of the two interventions. RESULTS: An additional 753 person years in the labour force would have been achieved from 1993 to 2003 for the male cohort aged 60-64 years in 2003, if a lifestyle intervention had been introduced in 1983; with 890 person years for the equivalent female group. The impact on labour force participation was lower for the metformin intervention, and increased with age for both interventions. The male cohort aged 60-64 years in 2003 would have earned an additional $30 million in income with the metformin intervention, and the equivalent female cohort would have earned an additional $25 million. If the lifestyle intervention was introduced, the same male and female cohorts would have earned an additional $34 million and $28 million respectively from 1993 to 2003. For the individuals involved, on average, males would have earned an additional $44,600 per year and females an additional $31,800 per year, if they had continued to work as a result of preventing diabetes. CONCLUSIONS: In addition to improved health and wellbeing, considerable benefits to individuals, in terms of both additional working years and increased personal income, could be made by introducing either a lifestyle or metformin intervention to prevent diabetes.

Individual and national financial impacts of informal caring for people with mental illness in Australia, projected to 2030.

BACKGROUND: Mental illness has a significant impact not only on patients, but also on their carers' capacity to work. AIMS: To estimate the costs associated with lost labour force participation due to the provision of informal care for people with mental illness in Australia, such as income loss for carers and lost tax revenue and increased welfare payments for government, from 2015 to 2030. METHOD: The output data of a microsimulation model Care&WorkMOD were analysed to project the financial costs of informal care for people with mental illness, from 2015 to 2030. Care&WorkMOD is a population-representative microsimulation model of the Australian population aged between 15 and 64 years, built using the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers data and the data from other population-representative microsimulation models. RESULTS: The total annual national loss of income for all carers due to caring for someone with mental illness was projected to rise from AU$451 million (£219.6 million) in 2015 to AU$645 million (£314 million) in 2030 in real terms. For the government, the total annual lost tax revenue was projected to rise from AU$121 million (£58.9 million) in 2015 to AU$170 million (£82.8 million) in 2030 and welfare payments to increase from AU$170 million (£82.8 million) to AU$220 million (£107 million) in 2030. CONCLUSIONS: The costs associated with lost labour force participation due to the provision of informal care for people with mental illness are projected to increase for both carers and government, with a widening income gap between informal carers and employed non-carers, putting carers at risk of increased inequality.