Deciphering the Acylation Pattern of Yersinia enterocolitica Lipid A

Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS) lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2)-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the reduced activation of the LPS receptor by a LpxR-dependent deacylated LPS.

The structure of compact disjointness preserving operators on continuous functions

Let T be a compact disjointness preserving linear operator from C0(X) into C0(Y), where X and Y are locally compact Hausdorff spaces. We show that T can be represented as a norm convergent countable sum of disjoint rank one operators. More precisely, T = Snd ?hn for a (possibly finite) sequence {xn }n of distinct points in X and a norm null sequence {hn }n of mutually disjoint functions in C0(Y). Moreover, we develop a graph theoretic method to describe the spectrum of such an operator

Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus

ObjectiveThe objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis.MethodsFifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D).ResultsOn the basis of the US results SLE patients were divided into three groups: erosive arthritis (n?=?20), non-erosive arthritis (n?=?18) and those with a normal US scan (n?=?12). Across the SLE groups plasma IL-6 levels correlated with CRP (p?

The Influence of Structural Modeshape Variability on Limit Cycle Oscillation Behaviour

Modal analysis is a popular approach used in structural dynamic and aeroelastic problems due to its efficiency. The response of a structure is compo
sed of the sum of orthogonal eigenvectors or modeshapes and corresponding modal frequencies. This paper investigates the importance of modeshapes on the aeroelastic response of the Goland wing subject to structural uncertainties. The wing undergoes limit cycle oscillations (LCO) as a result of the inclusion of polynomial stiffness nonlinearities. The LCO computations are performed using a Harmonic Balance approach for speed, the modal properties of the system are extracted from MSC NASTRAN. Variability in both the wing’s structure and the store centre of gravity location is investigated in two cases:- supercritical and subcritical type LCOs. Results show that the LCO behaviour is only sensitive to change in modeshapes when the nature of the modes are changing significantly.

Evaluation and mechanistic investigation of a AuPd alloy catalyst for the hydrocarbon selective catalytic reduction (HC-SCR) of NOx

The ability of a gold palladium bimetallic catalyst to selectively oxidise toluene has been used to enhance the hydrocarbon selective catalytic reduction of NOx, a reaction in which the interaction of partial oxidation intermediates is considered important. The combination of gold with palladium has a synergistic effect, producing a catalyst that is more active for NOx conversion than the arithmetic sum of the corresponding mono-metallic materials. Three regimes in the conversion profile of the AuPd catalyst are proposed relating to production and consumption of toluene derived species, such as benzaldehyde and benzonitrile. The possible role of these reaction intermediates in the toluene HC-SCR reaction is examined. Using 15NO, the formation of N2 and N2O is observed via the direct interaction between the nitrogen atom of benzonitrile and 15NO. The higher activity of the bimetallic catalyst for the NOx reduction reaction by toluene is discussed in the context of these partial oxidation intermediates.

Kinetics of levoglucosan and formaldehyde formation during cellulose pyrolysis process

The mechanisms and kinetics studies of the formation of levoglucosan and formaldehyde from anhydroglucose radical have been carried out theoretically in this paper. The geometries and frequencies of all the stationary points are calculated at the B3LYP/6-31+G(D,P) level based on quantum mechanics, Six elementary reactions are found, and three global reactions are involved. The variational transition-state rate constants for the elementary reactions are calculated within 450-1500 K. The global rate constants for every pathway are evaluated from the sum of the individual elementary reaction rate constants. The first-order Arrhenius expressions for these six elementary reactions and the three pathways are suggested. By comparing with the experimental data, computational methods without tunneling correction give good description for Path1 (the formation of levoglucosan); while methods with tunneling correction (zero-curvature tunneling and small-curvature tunneling correction) give good results for Path2 (the first possibility for the formation of formaldehyde), all the test methods give similar results for Path3 (the second possibility for the formation of formaldehyde), all the modeling results for Path3 are in good agreement with the experimental data, verifying that it is the most possible way for the formation of formaldehyde during cellulose pyrolysis. © 2012 Elsevier Ltd. All rights reserved.

Photocatalytic destruction of geosmin using novel pelleted titanium dioxide

Geosmin is produced by cyanobacteria and actinomycetes in surface waters. It causes undesirable earthy off-flavours in freshwater fish and is a major concern for the drinking water industry. This paper presents the first published study on the use of the novel pelleted Ti0₂ photocatalyst, Hombikat K01/C, for the removal of geosmin from water. Ti0₂ in pelleted form eliminates the requirement for the separation of the catalyst from the water following treatment which is normally the case with the widely used powdered catalysts. A laboratory reactor was designed to limit system loss since the compound adsorbs to a wide range of surfaces. Initial concentration, aeration rate and irradiation were evaluated. It was found that degradation of geosmin followed the Langmuir-Hinshelwood model. Elevated aeration had no effect on the photocatalytic removal of geosmin, but increasing irradiation was found to increase degradation rates. The catalyst proved effective within 10 min under optimum conditions. 

Untreated Mild Hyperglycemia During Pregnancy and Anthropometric Measures of Obesity in Offspring at Age 5-7 Years

OBJECTIVE: Obesity in the offspring of women with hyperglycemia during pregnancy has been reported, but the results are conflicting. This study examined the association of hyperglycemia during pregnancy and anthropometry in 5- to 7-year-old offspring whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study at the Belfast Centre.

RESEARCH DESIGN AND METHODS: Women in the HAPO study underwent a 75-g oral glucose tolerance test (OGTT) at approximately 28 weeks of gestation. Mothers and caregivers remained blinded to the results unless the fasting plasma glucose (FPG) concentration was >5.8 mmol/L or the 2-h plasma glucose (2hPG) concentration was >11.1 mmol/L. Offspring weight, height, and skin-fold thicknesses (triceps, subscapular, and suprailiac) were measured at age 5-7 years. Overweight, obesity, and extreme obesity were defined as a BMI z score ≥85th, ≥95th, and ≥99th percentile, respectively, based on the 1990 British Growth Standard.

RESULTS: Belfast HAPO offspring (n = 1,320, 82%) aged 5-7 years attended for follow-up. Using multiple regression, maternal FPG, 1h PG, and 2hPG did not show any relation to offspring BMI z score or offspring skin-fold sum independent of maternal BMI at OGTT and offspring birth weight z score. This lack of association with maternal glycemia persisted with the offspring BMI z score expressed as ≥85th, ≥95th, or 99th percentile, and the sum of skin folds expressed as ≥90th percentile specific for sex. The initially significant relation between FPG and all offspring adiposity measures was explained by maternal BMI at the OGTT.

CONCLUSIONS: After adjustment for maternal BMI at the OGTT, higher maternal FPG concentration during pregnancy (short of diabetes) is no longer a risk factor for obesity, as reflected by BMI and the sum of skin folds in offspring aged 5-7 years.

Storage of sediment-associated nutrients and contaminants in river channel and floodplain systems

Samples of fine-grained channel bed sediment and overbank floodplain deposits were collected along the main channels of the Rivers Aire (and its main tributary, the River Calder) and Swale, in Yorkshire, UK, in order to investigate downstream changes in the storage and deposition of heavy metals (Cr, Cu, Pb, Zn), total P and the sum of selected PCB congeners, and to estimate the total storage of these contaminants within the main channels and floodplains of these river systems. Downstream trends in the contaminant content of the <63 μm fraction of channel bed and floodplain sediment in the study rivers are controlled mainly by the location of the main sources of the contaminants, which varies between rivers. In the Rivers Aire and Calder, the contaminant content of the <63 μm fraction of channel bed and floodplain sediment generally increases in a downstream direction, reflecting the location of the main urban and industrialized areas in the middle and lower parts of the basin. In the River Swale, the concentrations of most of the contaminants examined are approximately constant along the length of the river, due to the relatively unpolluted nature of this river. However, the Pb and Zn content of fine channel bed sediment decreases downstream, due to the location of historic metal mines in the headwaters of this river, and the effect of downstream dilution with uncontaminated sediment. The magnitude and spatial variation of contaminant storage and deposition on channel beds and floodplains are also controlled by the amount of <63 μm sediment stored on the channel bed and deposited on the floodplain during overbank events. Consequently, contaminant deposition and storage are strongly influenced by the surface area of the floodplain and channel bed. Contaminant storage on the channel beds of the study rivers is, therefore, generally greatest in the middle and lower reaches of the rivers, since channel width increases downstream. Comparisons of the estimates of total storage of specific contaminants on the channel beds of the main channel systems of the study rivers with the annual contaminant flux at the catchment outlets indicate that channel storage represents <3% of the outlet flux and is, therefore, of limited importance in regulating that flux. Similar comparisons between the annual deposition flux of specific contaminants to the floodplains of the study rivers and the annual contaminant flux at the catchment outlet, emphasise the potential importance of floodplain deposition as a conveyance loss. In the case of the River Aire the floodplain deposition flux is equivalent to between ca. 2% (PCBs) and 36% (Pb) of the outlet flux. With the exception of PCBs, for which the value is ≅0, the equivalent values for the River Swale range between 18% (P) and 95% (Pb). The study emphasises that knowledge of the fine-grained sediment delivery system operating in a river basin is an essential prerequisite for understanding the transport and storage of sediment-associated contaminants in river systems and that conveyance losses associated with floodplain deposition exert an important control on downstream contaminant fluxes and the fate of such contaminants. © 2003 Elsevier Science Ltd. All rights reserved.

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

BACKGROUND: Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women.

METHODS: We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates.

RESULTS: DM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort.

CONCLUSIONS: Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.

Identification of Road Irregularities via Vehicle Accelerations

A periodic monitoring of the pavement condition facilitates a cost-effective distribution of the resources available for maintenance of the road infrastructure network. The task can be accurately carried out using profilometers, but such an approach is generally expensive. This paper presents a method to collect information on the road profile via accelerometers mounted in a fleet of non-specialist vehicles, such as police cars, that are in use for other purposes. It proposes an optimisation algorithm, based on Cross Entropy theory, to predict road irregularities. The Cross Entropy algorithm estimates the height of the road irregularities from vehicle accelerations at each point in time. To test the algorithm, the crossing of a half-car roll model is simulated over a range of road profiles to obtain accelerations of the vehicle sprung and unsprung masses. Then, the simulated vehicle accelerations are used as input in an iterative procedure that searches for the best solution to the inverse problem of finding road irregularities. In each iteration, a sample of road profiles is generated and an objective function defined as the sum of squares of differences between the ‘measured’ and predicted accelerations is minimized until convergence is reached. The reconstructed profile is classified according to ISO and IRI recommendations and compared to its original class. Results demonstrate that the approach is feasible and that a good estimate of the short-wavelength features of the road profile can be detected, despite the variability between the vehicles used to collect the data.

Abundance and diversity of sedimentary bacterial communities in a coastal productive setting in the Western Irish Sea

The bacterial community composition and biomass abundance from a depositional mud belt in the western Irish Sea and regional sands were investigated by phospholipid ester-linked fatty acid profiling, denaturing gradient gel electrophoresis and barcoded pyrosequencing of 16S rRNA genes. The study area varied by water depth (12-111 m), organic carbon content (0.09-1.57% TOC), grain size, hydrographic regime (well-mixed vs. stratified), and water column phytodetrital input (represented by algal polyunsaturated PLFA). The relative abundance of bacterial-derived PLFA (sum of methyl-branched, cyclopropyl and odd-carbon number PLFA) was positively correlated with fine-grained sediment, and was highest in the depositional mud belt. A strong association between bacterial biomass and eukaryote primary production was suggested based on observed positive correlations with total nitrogen and algal polyunsaturated fatty acids. In addition, 16S rRNA genes affiliated to the classes Clostridia and Flavobacteria represented a major proportion of total 16S rRNA gene sequences. This suggests that benthic bacterial communities are also important degraders of phytodetrital organic matter and closely coupled to water column productivity in the western Irish Sea.

Contracts for the Sale of Land: Understanding the Impecuniosity Defence

Where either the seller or buyer of landed property fails to complete a contract to sell land the non-breaching party has a right to seek specific performance of the contract. This remedy would compel the party in default to perform the contract on pain of being held in contempt of court if the court's order is not obeyed. The defaulting party would not be able to satisfy its obligations under the law by paying a sum of money as damages for breach of contract. This paper considers the impecuniosity defence to specific performance as recognised by courts in Northern Ireland, the Republic of Ireland, Australia and New Zealand. Where the buyer demonstrates that he or she simply cannot raise the funds to buy the property specific performance will not be decreed and the court will make an award of damages for breach of contract measured by the difference between the contract price and the market price of the property at the time of default. The paper considers the nature and parameters of this defence and how it differs (if at all) from the alternative defence of extreme hardship. The paper addresses the question of whether it might be better to move to a position where sellers of land in all cases no longer enjoy a presumption of specific performance but have to demonstrate that the alternative remedy of damages is clearly inadequate. If this should be so the paper goes on to consider whether abolition of the presumption in favour of specific performance for sellers should lead to abolition of the presumption of specific performance for buyers, as is the position in Canada following the Supreme Court's decision in Semelhago v Paramadevan [1996] 2 SCR 415.

Electron impact fragmentation of thymine:partial ionization cross sections for positive fragments

We have measured mass spectra for positive ions for low-energy electron impact on thymine using a reflectron time-of-flight mass spectrometer. Using computer controlled data acquisition, mass spectra have been acquired for electron impact energies up to 100 eV in steps of 0.5 eV. Ion yield curves for most of the fragment ions have been determined by fitting groups of adjacent peaks in the mass spectra with sequences of normalized Gaussians. The ion yield curves have been normalized by comparing the sum of the ion yields to the average of calculated total ionization cross sections. Appearance energies have been determined. The nearly equal appearance energies of 83 u and 55 u observed in the present work strongly indicate that near threshold the 55 u ion is formed directly by the breakage of two bonds in the ring, rather than from a successive loss of HNCO and CO from the parent ion. Likewise 54 u is not formed by CO loss from 82 u. The appearance energies are in a number of cases consistent with the loss of one or more hydrogen atoms from a heavier fragment, but 70 u is not formed by hydrogen loss from 71 u.

Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe

BACKGROUND: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.

METHODS: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes.

RESULTS: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%).

CONCLUSIONS: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden.