Lipopolysaccharide-specific acyloxyacyl hydrolase

" An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids from their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being being bound in turn to lipopolysaccharide glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight by gel exclusion chromatography between about 50,000 Daltons and about 70,000 Daltons, and a molecular weight by polyacrylamide gel electrophoresis with sodium dodecylsulphate, using reduced molecular weight standards, of approximately 54,000 to 60,000 Daltons. Altered bacterial lipopolysaccharide substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of lipopolysaccharide lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on lipopolysaccharide of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria). Such altered bacterial lipopolysaccharide, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to lipopolysaccharide O-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent Gram-negative bacterial sepsis (""septic shock""), or (3) as adjuvants to enhance formation of antibodies to other antigens. the acyloxyacyl hydrolase itself may be prophylactically or therapeutically useful to detoxify endogenous lipopolysaccharide in patients with Gram-negative bacterial diseases. The enzyme may also be used to remove toxic lipopolysaccharide from therapeutic injectants. "Board of Regents, University of Texas Syste

Estimating the additional costs of living with a disability in the United Kingdom between 2013 and 2016

In the United Kingdom, more than 20% of the population live with a disability. Past evidence shows that being disabled is associated with functional limitations that often cause social exclusion and poverty. Therefore, it is necessary to analyse the connection between disability and poverty. This paper examines whether households with disabled members face extra costs of living to attain the same standard of living as their peers without disabled members. The modelling framework is based on the standard of living approach which estimates the extra income required to close the gap between households with and without disabled members. We apply an ordered logit regression to data from the Family Resources Survey between 2013 and 2016 to analyse the relationship between standard of living, income, and disability, conditional on other explanatory variables. We find that households with disabled members face considerable extra costs that go beyond the transfer payment of the government. The average household with disabled members saw their weekly extra costs continually increase from £293 in 2013 to £326 in 2016 [2020 prices]. Therefore, the government needs to adjust welfare policies to address the problem of extra costs faced by households with disabled members

Does commuting mode choice impact health?

Governments around the world are encouraging people to switch away from sedentary modes of travel towards more active modes, including walking and cycling. The aim of these schemes is to improve population health and to reduce emissions. There is considerable evidence on the latter, yet relatively little on the former. This paper investigates the impact of mode choice on measures of physical and mental health as well as satisfaction with health. Using data from the UK Household Longitudinal Study from 2009-2016, our empirical strategy exploits changes in the mode of commute to identify health outcome responses. Individuals who change modes are matched with those whose mode remains constant. Overall we find that mode switches affect both physical and mental health. Specifically we find an increase in physical health for women and an increase in mental health for both genders, when switching from car to active travel. In contrast, both men and women who switch from active travel to car are shown to experience a significant reduction in their physical health and health satisfaction, and a decline in their mental health when they change from active to public transport

Analysing changes to the flow of public funding within local health and care systems: An adaptation of the System of Health Accounts framework to a local health system in England

Financial flows relating to health care are routinely analysed at national and international level. They have rarely been systematically analysed at local level, despite sub-national variation due to population needs and decisions enacted by local organisations. We illustrate an adaptation of the System of Health Accounts framework to map the flow of public health and care funding within local systems, with an application for Greater Manchester (GM), an area in England which agreed a health and social care devolution deal with the central government in 2016. We analyse how financial flows changed in GM during the four years post-devolution, and whether spending was aligned with local ambitions to move towards prevention of ill-health and integration of health and social care. We find that GM decreased spending on public health by 15%, and increased spending on general practice by 0.1% in real terms. The share of total local expenditure paid to NHS Trusts for general and acute services increased from 70.3% to 71.6%, while that for community services decreased from 11.7% to 10.3%. Results suggest that GM may have experienced challenges in redirecting resources towards their goals. Mapping financial flows at a local level is a useful exercise to examine whether spending is aligned with system goals and highlight areas for further investigation

Election outcomes and individual subjective well-being in Great Britain

Exploiting novel longitudinal data on individuals in Great Britain matched to their parliamentary constituency, we find that supporting the incumbent political party, at both the national and constituency levels, exerts a positive influence on individual subjective wellbeing. This relationship varies across different measures of subjective wellbeing, gender and personal characteristics. We then implement a regression discontinuity in time design to estimate the impact of a quasi‐natural experiment, where we exploit the timing of the survey around the 2010 election date in order to identify a causal relationship. We find that Liberal Democrat supporters have approximately one‐unit higher level of overall life satisfaction after their party’s electoral success

Stimulus-dependent Deacylation of Bacterial Lipopolysaccharide by Dendritic Cells

We describe here a previously unrecognized property of dendritic cells (DCs), the ability to deacylate the lipid A moiety of gram-negative bacterial LPSs. Both immature DCs of the XS52 cell line and bone marrow–derived DCs produce acyloxyacyl hydrolase, an enzyme that detoxifies LPS by selectively removing the secondary acyl chains from lipid A. Acyloxyacyl hydrolase expression decreased when DCs were incubated with IL-4, IL-1β, TNFα, and an agonistic CD40 antibody (maturation cocktail), and increased after treatment with LPS, CpG oligodeoxynucleotides, or a gram-positive bacterium (Micococcus luteus). Maturation cocktail treatment also diminished, whereas LPS treatment enhanced or maintained the cells' ability to kill Escherichia coli, deacylate LPS, and degrade bacterial protein. Enzymatic deacylation of LPS is an intrinsic, regulated mechanism by which DCs may modulate host responses to this potent bacterial agonist

The disutility of commuting? The effect of gender and local labour markets

Commuting is an extremely important modern phenomenon characterised by the spatial interaction of housing and labour markets. The average commuter in the UK spends nearly an hour a day travelling to and from employment. Standard economic theory postulates that commuting is a choice behaviour undertaken when compensated through either lower rents or greater amenities in the housing market or through greater wages in the labour market. By exploiting exogenous shocks to commuting time, this paper investigates the impact on wellbeing of increased commuting. Ceteris paribus, exogenous increases in commuting time are expected to lower wellbeing. We find this holds for women but not men. This phenomenon can be explained, in part, by the different labour markets in which women operate. Where local labour markets are thin, women report significantly lower wellbeing when faced with an increased commute. This does not hold for tight local labour markets. Further our findings reveal that it is full-time working women in the managerial and professional tier of the occupational hierarchy who are most affected

Multidimensional Gaussian sums arising from distribution of Birkhoff sums in zero entropy dynamical systems

A duality formula, of the Hardy and Littlewood type for multidimensional Gaussian sums, is proved in order to estimate the asymptotic long time behavior of distribution of Birkhoff sums $S_n$ of a sequence generated by a skew product dynamical system on the $\mathbb{T}^2$ torus, with zero Lyapounov exponents. The sequence, taking the values $\pm 1$, is pairwise independent (but not independent) ergodic sequence with infinite range dependence. The model corresponds to the motion of a particle on an infinite cylinder, hopping backward and forward along its axis, with a transversal acceleration parameter $\alpha$. We show that when the parameter $\alpha /\pi$ is rational then all the moments of the normalized sums $E((S_n/\sqrt{n})^k)$, but the second, are unbounded with respect to n, while for irrational $\alpha /\pi$, with bounded continuous fraction representation, all these moments are finite and bounded with respect to n.Comment: To be published in J. Phys.