Cortisol levels in response to starting school in children at increased risk for social phobia

Background: Research on depression has identified hyperactivity of the HPA axis as a potential contributory factor to the intergenerational transmission of affective symptoms. However, this has not yet been examined in the context of social phobia. The current study compared HPA axis activity in response to a universal social stressor (starting school) in children of 2 groups of women: one with social phobia and one with no history of anxiety (comparison group). To determine specificity of effects of maternal social phobia, a third group of children were also examined whose mothers had generalised anxiety disorder (GAD). Method: Children provided salivary cortisol samples in the morning, afternoon and at bedtime across 3 time-blocks surrounding the school start: a month before starting school (baseline), the first week at school (stress response), and the end of the first school term (stress recovery). Child behavioural inhibition at 14 months was also assessed to explore the influence of early temperament on later stress responses. Results: All children displayed an elevation in morning and afternoon cortisol from baseline during the first week at school, which remained elevated until the end of the first term. Children in the social phobia group, however, also displayed an equivalent elevation in bedtime cortisol, which was not observed for comparison children or for children of mothers with GAD. Children in the social phobia group who were classified as 'inhibited' at 14 months displayed significantly higher afternoon cortisol levels overall. Summary: A persistent stress response to school in the morning and afternoon is typical for all children, but children of mothers with social phobia also display atypical elevations in evening cortisol levels when at school - signalling long-term disruption of the circadian rhythm in HPA axis activity. This is the first study to report HPA axis disruption in children at risk of developing social phobia, and future research should aim to determine whether this represents a pathway for symptom development, taking early temperament into account.

Riluzole elevates GLT-1 activity and levels in striatal astrocytes

Drugs which upregulate astrocyte glutamate transport may be useful neuroprotective compounds by preventing excitotoxicity. We set up a new system to identify potential neuroprotective drugs which act through GLT-1. Primary mouse striatal astrocytes grown in the presence of the growth-factor supplement G5 express high levels of the functional glutamate transporter, GLT-1 (also known as EAAT2) as assessed by Western blotting and (3)H-glutamate uptake assay, and levels decline following growth factor withdrawal. The GLT-1 transcriptional enhancer dexamethasone (0.1 or 1muM) was able to prevent loss of GLT-1 levels and activity following growth factor withdrawal. In contrast, ceftriaxone, a compound previously reported to enhance GLT-1 expression, failed to regulate GLT-1 in this system. The neuroprotective compound riluzole (100muM) upregulated GLT-1 levels and activity, through a mechanism that was not dependent on blockade of voltage-sensitive ion channels, since zonasimide (1mM) did not regulate GLT-1. Finally, CDP-choline (10muM-1mM), a compound which promotes association of GLT-1/EAAT2 with lipid rafts was unable to prevent GLT-1 loss under these conditions. This observation extends the known pharmacological actions of riluzole, and suggests that this compound may exert its neuroprotective effects through an astrocyte-dependent mechanism.

Semi-dwarfing (Rht-B1b) improves nitrogen-use efficiency in wheat, but not at economically optimal levels of nitrogen availability

A UK field experiment compared a complete factorial combination of three backgrounds (cvs Mercia, Maris Huntsman and Maris Widgeon), three alleles at the Rht-B1 locus as Near Isogenic Lines (NILs: rht-B1a (tall), Rht-B1b (semi-dwarf), Rht-B1c (severe dwarf)) and four nitrogen (N) fertilizer application rates (0, 100, 200 and 350 kg N/ha). Linear+exponential functions were fitted to grain yield (GY) and nitrogen-use efficiency (NUE; GY/available N) responses to N rate. Averaged over N rate and background Rht-B1b conferred significantly (P<0.05) greater GY, NUE, N uptake efficiency (NUpE; N in above ground crop / available N) and N utilization efficiency (NUtEg; GY / N in above ground crop) compared with rht-B1a and Rht-B1c. However the economically optimal N rate (Nopt) for N:grain price ratios of 3.5:1 to 10:1 were also greater for Rht-B1b, and because NUE, NUpE and NUtE all declined with N rate, Rht-Blb failed to increase NUE or its components at Nopt. The adoption of semi-dwarf lines in temperate and humid regions, and the greater N rates that such adoption justifies economically, greatly increases land-use efficiency, but not necessarily, NUE.

Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma fatty acid levels and insulin resistance

Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects. Methods and results: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. Conclusion: The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.

Forecasting annual inflation with seasonal monthly data: using levels versus logs of the underlying price index

This paper investigates whether using natural logarithms (logs) of price indices for forecasting inflation rates is preferable to employing the original series. Univariate forecasts for annual inflation rates for a number of European countries and the USA based on monthly seasonal consumer price indices are considered. Stochastic seasonality and deterministic seasonality models are used. In many cases, the forecasts based on the original variables result in substantially smaller root mean squared errors than models based on logs. In turn, if forecasts based on logs are superior, the gains are typically small. This outcome sheds doubt on the common practice in the academic literature to forecast inflation rates based on differences of logs.

Frying of potato chips in a blend of canola oil and palm olein: changes in levels of individual fatty acids and tocols

The changes occurring in the levels of nutritionally relevant oil components were assessed during repeated frying of potato chips in a blend of palm olein and canola oil (1:1 w/w). The blend suffered minimal reductions in omega-3 and omega-6 polyunsaturated fatty acids. There was no significant difference between the fatty acid composition of the oil extracted from the product and that of the frying medium, in all three cases. The blend also contained a significant amount of tocols which add a nutritional value to the oil. The concentration of the tocols was satisfactorily retained over the period of oil usage, in contrast to the significant loses observed in the case of the individual oils. The blend also performed well when assessed by changes in total polar compounds, free fatty acids, p-anisidine value. When fried in used oil, the product oil content increased progressively with oil usage time. This study shows that blended frying oils can combine good stability and nutritional quality

Automatic near real-time selection of flood water levels from high resolution Synthetic Aperture Radar images for assimilation into hydraulic models: a case study

Flood extents caused by fluvial floods in urban and rural areas may be predicted by hydraulic models. Assimilation may be used to correct the model state and improve the estimates of the model parameters or external forcing. One common observation assimilated is the water level at various points along the modelled reach. Distributed water levels may be estimated indirectly along the flood extents in Synthetic Aperture Radar (SAR) images by intersecting the extents with the floodplain topography. It is necessary to select a subset of levels for assimilation because adjacent levels along the flood extent will be strongly correlated. A method for selecting such a subset automatically and in near real-time is described, which would allow the SAR water levels to be used in a forecasting model. The method first selects candidate waterline points in flooded rural areas having low slope. The waterline levels and positions are corrected for the effects of double reflections between the water surface and emergent vegetation at the flood edge. Waterline points are also selected in flooded urban areas away from radar shadow and layover caused by buildings, with levels similar to those in adjacent rural areas. The resulting points are thinned to reduce spatial autocorrelation using a top-down clustering approach. The method was developed using a TerraSAR-X image from a particular case study involving urban and rural flooding. The waterline points extracted proved to be spatially uncorrelated, with levels reasonably similar to those determined manually from aerial photographs, and in good agreement with those of nearby gauges.

Intracellular accumulation of high levels of gamma-aminobutyrate by Listeria monocytogenes 10403S in response to low pH: uncoupling of gamma-aminobutyrate synthesis from efflux in a chemically defined medium

It is well established that the glutamate decarboxylase (GAD) system is central to the survival of Listeria monocytogenes at low pH, both in acidic foods and within the mammalian stomach. The accepted model proposes that under acidic conditions extracellular glutamate is transported into the cell in exchange for an intracellular gamma-aminobutyrate (GABA(i)). The glutamate is then decarboxylated to GABA(i), a reaction that consumes a proton, thereby helping to prevent acidification of the cytoplasm. In this study, we show that glutamate supplementation had no influence on either growth rate at pH 5.0 or survival at pH 2.5 when L. monocytogenes 10403S was grown in a chemically defined medium (DM). In response to acidification, cells grown in DM failed to efflux GABA, even when glutamate was added to the medium. In contrast, in brain heart infusion (BHI), the same strain produced significant extracellular GABA (GABA(e)) in response to acidification. In addition, high levels of GABA(i) (>80 mM) were found in the cytoplasm in response to low pH in both growth media. Medium-swap and medium-mixing experiments revealed that the GABA efflux apparatus was nonfunctional in DM, even when glutamate was present. It was also found that the GadT2D2 antiporter/decarboxylase system was transcribed poorly in DM-grown cultures while overexpression of gadD1T1 and gadD3 occurred in response to pH 3.5. Interestingly, BHI-grown cells did not respond with upregulation of any of the GAD system genes when challenged at pH 3.5. The accumulation of GABA(i) in cells grown in DM in the absence of extracellular glutamate indicates that intracellular glutamate is the source of the GABA(i). These results demonstrate that GABA production can be uncoupled from GABA efflux, a finding that alters the way we should view the operation of bacterial GAD systems.

Effect on components of the intestinal microflora and plasma neuropeptide levels of feeding Lactobacillus delbrueckii, Bifidobacterium lactis, and inulin to adult and elderly rats

The aim of this study was to compare the effects of the mixture of Lactobacillus delbrueckii subsp. rhamnosus strain GG, Bifidobacterium lactis Bb12, and inulin on intestinal populations of lactobacilli, bifidobacteria, and enterobacteria in adult and elderly rats fed the same (in quality and quantity) diet. The portal plasma levels of two neuropeptides, neuropeptide Y (NPY) and peptide YY (PYY), were also evaluated to assess the physiological consequences of the synbiotic treatment for the gastrointestinal (GI) tracts of rats of different ages. Adult (n = 24) and elderly (n = 24) male rats were fed the AIN-93 M maintenance diet. After 2 weeks of adaptation, the diet of 12 rats of each age group was supplemented with 8% inulin and with strains GG and Bb12 to provide 2.2 x 10(9) CFU of each strain g(-1) of the diet. Blood and different regions of the GI tract were sampled from all rats after 21 days of the treatment. Treatment with the mixture of strain GG, strain BB12, and inulin induced significantly different changes in the numbers of lactobacilli, bifidobacteria, and enterobacteria of the stomach, small intestine, cecum, and colon microflora. Moreover, the GG, BB12, and inulin mixture increased the concentrations of NPY and PYY for adult rats. For the elderly animals, the PYY concentration was not changed, while the NPY concentration was decreased by treatment with the GG, BB12, and inulin mixture. The results of the present study indicate that the physiological status of the GI tract, and not just diet, has a major role in the regulation of important groups of the GI bacteria community, since even the outcome of the dietary modification with synbiotics depends on the ages of the animals.

Elevated levels of corticotrophin-releasing factor binding protein in the blood of patients suffering from arthritis and septicaemia and the presence of novel ligands in synovial fluid.

In view of the reported inflammatory effects of corticotrophin-releasing factor (CRF) and the associated regulatory elements in the gene of its binding protein (BP), we postulate that both BP as well as novel BP-ligands other than CRF may be involved in inflammatory disease. We have investigated BP in the blood of patients with arthritis and septicaemia and have attempted to identify CRF and other BP-ligands in synovial fluid. The BP was found to be significantly elevated in the blood of patients with rheumatoid arthritis and septicaemia. There was less BP-ligand and CRF in synovial fluid from patients with rheumatoid arthritis that from those with osteo- or psoriatic arthritis. There was at least 10-fold more BP-ligand than CRF in the fluid of all three groups of patients. A small amount of immunoreactive human (h)CRF, eluting in the expected position of CRF-41, was detected after high-pressure liquid chromatography of arthritic synovial fluid; however, the bulk of material with BP-ligand binding activity eluted earlier, suggesting that synovial fluid contained novel peptides that interacted with the BP. These results would suggest that the BP and its ligands could play an endocrine immunomodulatory role in inflammatory disease.

Enhanced levels of cold shock proteins in Listeria monocytogenes LO28 upon exposure to low temperature and high hydrostatic pressure

Listeria monocytogenes is a psychrotrophic food-borne pathogen that is problematic for the food industry because of its ubiquitous distribution in nature and its ability to grow at low temperatures and in the presence of high salt concentrations. Here we demonstrate that the process of adaptation to low temperature after cold shock includes elevated levels of cold shock proteins (CSPs) and that the levels of CSPs are also elevated after treatment with high hydrostatic pressure (HHP). Two-dimensional gel electrophoresis combined with Western blotting performed with anti-CspB of Bacillus subtilis was used to identify four 7-kDa proteins, designated Csp1, Csp2, Csp3, and Csp4. In addition, Southern blotting revealed four chromosomal DNA fragments that reacted with a csp probe, which also indicated that a CSP family is present in L. monocytogenes LO28. After a cold shock in which the temperature was decreased from 37°C to 10°C the levels of Csp1 and Csp3 increased 10- and 3.5-fold, respectively, but the levels of Csp2 and Csp4 were not elevated. Pressurization of L. monocytogenes LO28 cells resulted in 3.5- and 2-fold increases in the levels of Csp1 and Csp2, respectively. Strikingly, the level of survival after pressurization of cold-shocked cells was 100-fold higher than that of cells growing exponentially at 37°C. These findings imply that cold-shocked cells are protected from HHP treatment, which may affect the efficiency of combined preservation techniques.