The acceptability of isoflavones as a treatment of menopausal symptoms: a European survey among postmenopausal women

Objective: To investigate determinants of the acceptability of isoflavone products among postmenopausal women with regard to social and lifestyle factors, dietary habits, health concerns, food beliefs, menopausal symptoms and therapies, and to elucidate preferences for specific products. Methods: A consumer survey was conducted among postmenopausal women in four European countries (Germany, Denmark, Italy and the UK), including a total of 465 respondents. Results: The declared acceptability of isoflavones was highest in Germany (80%), followed by Italy (75%), the UK (59%) and Denmark (55%; p < 0.001). Among other factors, prior information about isoflavones (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.54-4.51, p < 0.001) and belief that foods can be used to treat medical conditions (OR 2.18, 95% CI 1.17-4.05, p=0.014) were the strongest predictors of potential acceptability. The preferred forms in which isoflavones might be taken differed markedly between countries. Conclusions: Information about the health effects of isoflavones and health-diet links should be considered the most important factors in attempts to influence the potential acceptability of isoflavone products. Foods enriched with isoflavones need to be developed with regard to specific cultural demands in order to assure consumer acceptance on the marketplace.

Differential recognition of Staphylococcus aureus quorum-sensing signals depends on both extracellular loops 1 and 2 of the transmembrane sensor AgrC.

Virulence in Staphylococcus aureus is regulated via agr-dependent quorum sensing in which an autoinducing peptide (AIP) activates AgrC, a histidine protein kinase. AIPs are usually thiolactones containing seven to nine amino acid residues in which the thiol of the central cysteine is linked to the alpha-carboxyl of the C-terminal amino acid residue. The staphylococcal agr locus has diverged such that the AIPs of the four different S. aureus agr groups self-activate but cross-inhibit. Consequently, although the agr system is conserved among the staphylococci, it has undergone significant evolutionary divergence whereby to retain functionality, any changes in the AIP-encoding gene (agrD) that modifies AIP structure must be accompanied by corresponding changes in the AgrC receptor. Since AIP-1 and AIP-4 only differ by a single amino acid, we compared the transmembrane topology of AgrC1 and AgrC4 to identify amino acid residues involved in AIP recognition. As only two of the three predicted extracellular loops exhibited amino acid differences, site-specific mutagenesis was used to exchange the key AgrC1 and AgrC4 amino acid residues in each loop either singly or in combination. A novel lux-based agrP3 reporter gene fusion was constructed to evaluate the response of the mutated AgrC receptors. The data obtained revealed that while differential recognition of AIP-1 and AIP-4 depends primarily on three amino acid residues in loop 2, loop 1 is essential for receptor activation by the cognate AIP. Furthermore, a single mutation in the AgrC1 loop 2 resulted in conversion of (Ala5)AIP-1 from a potent antagonist to an activator, essentially resulting in the forced evolution of a new AIP group. Taken together, our data indicate that loop 2 constitutes the predicted hydrophobic pocket that binds the AIP thiolactone ring while the exocyclic amino acid tail interacts with loop 1 to facilitate receptor activation.

Avaliação de duas técnicas de reação em cadeia da polimerase na detecção do Mycobacterium tuberculosis em diferentes amostras biológicas

A tuberculose (TB) é uma doença infecto-contagiosa causada pelo bacilo Mycobacterium tuberculosis e que permanece como um importante problema de saúde pública mundial, sendo a TB pulmonar a forma mais comum de apresentação da doença. O diagnóstico precoce e tratamento adequado são essenciais para a eficácia dos programas públicos de controle da TB. Novos metodologias mais rápidas, sensíveis e específicas, como a reação em cadeia da polimerase (PCR), vem sendo propostas no diagnóstico da doença. O objetivo desse estudo foi avaliar o desempenho de duas PCR, a PCR em tempo real (qPCR) e a Nested PCR em único tubo (STNPCR), em diferentes amostras biológicas, no diagnóstico da tuberculose pulmonar, além de compará-las com as metodologias convencionais (baciloscopia e cultura) e entre si. Para isso foram analisados 125 pacientes que tiveram amostras de sangue (125 amostras de plasma e 116 amostras de PBMC), urina (n=125) e escarro (n=125) coletadas, totalizando a análise de 491 amostras biológicas. Amostras de escarro e urina foram descontaminadas pelo método de Petroff NAOH 4 por cento modificado e semeadas em meio de cultura Lõwenstein-Jensen (LJ), enquanto as amostras de sangue eram separadas em plasma e PBMC. Após processamento, deu-se a extração de DNA através do kit comercial da Qiagen seguida de amplificação pelas duas metodologias de PCR. Para análise estatística calculou-se a sensibilidade, especificidade, valores preditivos positivo e negativo e índice kappa das técnicas. A STNPCR apresentou, em amostras de sangue, sensibilidade de 26,3 por cento e especificidade de 97,7 por cento. Em amostras de urina observou-se uma S = 7,9 por cento e E = 98,9 por cento e em escarro S = 21,1 por cento e E = 98,9 por cento. Quando analisadas as asmotras em paralelo, a sensibilidade da STNPCR foi igual a 44,7 por cento enquanto sua especificidade foi 97,7 por cento. Já a qPCR, em amostras de sangue, obteve sensibilidade igual a 26,3 por cento e especificidade de 95,4 por cento. Em amostras de urina a sensibilidade obtida foi 47,4 por cento e a especificidade 79,3 por cento e, em escarro, S = 36,8 por cento e E = 95,4 por cento. Quando analisada em paralelo, a sensibilidade da qPCR foi 65,8 por cento e a especificidade foi 79,3 por cento. A baciloscopia de escarro apresentou sensibilidade de 41,7 por cento e especificidade de 100 por cento, enquanto as culturas em urina e escarro apresentaram sensibilidade e especificidade, respectivamente, de 10,5 por cento e 100 por cento e 60,5 por cento e 96,6 por cento. Pode-se concluir que a qPCR apresentou melhor desempenho quando comparada à STNPCR e também bom desempenho quando comparada às metodologias convencionais, e que quando analisa-se mais de um tipo de amostras biológica, a eficácia das técnicas é aumentada. Espera-se que com a utilização dessa técnica molecular, seja possível a melhor elucidação dos casos de TB pulmonar, promovendo maior taxa de tratamento dos pacientes e menor risco de transmissão da doença

The competitive ability of pea-barley intercrops against weeds and the interactions with crop productivity and soil N availability

Grain legumes, such as peas (Pisum sativum L.), are known to be weak competitors against weeds when grown as the sole crop. In this study, the weed-suppression effect of pea–barley (Hordeum vulgare L.)intercropping compared to the respective sole crops was examined in organic field experiments across Western Europe (i.e., Denmark, the United Kingdom, France, Germany and Italy). Spring pea (P) and barley(B) were sown either as the sole crop, at the recommended plant density (P100 and B100, respectively), or in replacement (P50B50) or additive (P100B50)intercropping designs for three seasons (2003–2005). The weed biomass was three times higher under the pea sole crops than under both the intercrops and barley sole crops at maturity. The inclusion of joint experiments in several countries and various growing conditions showed that intercrops maintain a highly asymmetric competition over weeds, regardless of the particular weed infestation (species and productivity), the crop biomass or the soil nitrogen availability. The intercropping weed suppression was highly resilient, whereas the weed suppression in pea sole crops was lower and more variable. The pea–barley intercrops exhibited high levels of weed suppression, even with a low percentage of barley in the total biomass. Despite a reduced leaf area in the case of a low soil N availability, the barley sole crops and intercrops displayed high weed suppression, probably because of their strong competitive capability to absorb soil N. Higher soil N availabilities entailed increased leaf areas and competitive ability for light, which contributed to the overall competitive ability against weeds for all of the treatments. The contribution of the weeds in the total dry matter and soil N acquisition was higher in the pea sole crop than in the other treatments, in spite of the higher leaf areas in the pea crops.

The conditional performance of UK property funds

The evaluation of investment fund performance has been one of the main developments of modern portfolio theory. Most studies employ the technique developed by Jensen (1968) that compares a particular fund's returns to a benchmark portfolio of equal risk. However, the standard measures of fund manager performance are known to suffer from a number of problems in practice. In particular previous studies implicitly assume that the risk level of the portfolio is stationary through the evaluation period. That is unconditional measures of performance do not account for the fact that risk and expected returns may vary with the state of the economy. Therefore many of the problems encountered in previous performance studies reflect the inability of traditional measures to handle the dynamic behaviour of returns. As a consequence Ferson and Schadt (1996) suggest an approach to performance evaluation called conditional performance evaluation which is designed to address this problem. This paper utilises such a conditional measure of performance on a sample of 27 UK property funds, over the period 1987-1998. The results of which suggest that once the time varying nature of the funds beta is corrected for, by the addition of the market indicators, the average fund performance show an improvement over that of the traditional methods of analysis.

Toward understanding of differences in current cloud retrievals of ARM ground-based measurements

Accurate observations of cloud microphysical properties are needed for evaluating and improving the representation of cloud processes in climate models and better estimate of the Earth radiative budget. However, large differences are found in current cloud products retrieved from ground-based remote sensing measurements using various retrieval algorithms. Understanding the differences is an important step to address uncertainties in the cloud retrievals. In this study, an in-depth analysis of nine existing ground-based cloud retrievals using ARM remote sensing measurements is carried out. We place emphasis on boundary layer overcast clouds and high level ice clouds, which are the focus of many current retrieval development efforts due to their radiative importance and relatively simple structure. Large systematic discrepancies in cloud microphysical properties are found in these two types of clouds among the nine cloud retrieval products, particularly for the cloud liquid and ice particle effective radius. Note that the differences among some retrieval products are even larger than the prescribed uncertainties reported by the retrieval algorithm developers. It is shown that most of these large differences have their roots in the retrieval theoretical bases, assumptions, as well as input and constraint parameters. This study suggests the need to further validate current retrieval theories and assumptions and even the development of new retrieval algorithms with more observations under different cloud regimes.

Design of delay-tolerant linear dispersion codes

In cooperative communication networks, owing to the nodes' arbitrary geographical locations and individual oscillators, the system is fundamentally asynchronous. This will damage some of the key properties of the space-time codes and can lead to substantial performance degradation. In this paper, we study the design of linear dispersion codes (LDCs) for such asynchronous cooperative communication networks. Firstly, the concept of conventional LDCs is extended to the delay-tolerant version and new design criteria are discussed. Then we propose a new design method to yield delay-tolerant LDCs that reach the optimal Jensen's upper bound on ergodic capacity as well as minimum average pairwise error probability. The proposed design employs stochastic gradient algorithm to approach a local optimum. Moreover, it is improved by using simulated annealing type optimization to increase the likelihood of the global optimum. The proposed method allows for flexible number of nodes, receive antennas, modulated symbols and flexible length of codewords. Simulation results confirm the performance of the newly-proposed delay-tolerant LDCs.

The bile acid receptor TGR5 does not interact with β-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts.

TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid, DCA, taurolithocholic acid, TLCA) and the selective agonists oleanolic acid (OA) and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide (CCDC) stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, assessed by confocal microscopy. DCA, TLCA and OA did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, determined by bioluminescence resonance energy transfer. CCDC stimulated a low level of TGR5 interaction with β-arrestin2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of extracellular signal regulated kinase (ERK1/2). BRET analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.

Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

A review of the performance of different ventilation and airflow distribution systems in buildings

The objective of this article is to review the scientific literature on airflow distribution systems and ventilation effectiveness to identify and assess the most suitable room air distribution methods for various spaces. In this study, different ventilation systems are classified according to specific requirements and assessment procedures. This study shows that eight ventilation methods have been employed in the built environment for different purposes and tasks. The investigation shows that numerous studies have been carried out on ventilation effectiveness but few studies have been done regarding other aspects of air distribution. Amongst existing types of ventilation systems, the performance of each ventilation methods varies from one case to another due to different usages of the ventilation system in a room and the different assessment indices used. This review shows that the assessment of ventilation effectiveness or efficiency should be determined according to each task of the ventilation system, such as removal of heat, removal of pollutant, supply fresh air to the breathing zone or protecting the occupant from cross infection. The analysis results form a basic framework regarding the application of airflow distribution for the benefit of designers, architects, engineers, installers and building owners.

In optics humidity compensation in NDIR exhaust gas measurements of NO2

NDIR is proposed for monitoring of air pollutants emitted by ship engines. Careful optical filtering overcomes the challenge of optical detection of NO2 in humid exhaust gas, despite spectroscopic overlap with the water vapour band.

Investigation of Petasis and Ugi reactions in series in an automated microreactor system

Petasis and Ugi reactions are used successively without intermediate purification, effectively accomplishing a six-component reaction. The examined reactions are transferred from traditional batch reactors to an automated continuous flow microreactor setup, where optimization and kinetic analyses are performed, proposed mechanisms evaluated, and rate-limiting steps determined.

Impact of dietary polydextrose fiber on the human gut metabolome

The aim of the present study was to elucidate the impact of polydextrose PDX an soluble fiber, on the human fecal metabolome by high-resolution nuclear magnetic resonance (NMR) spectroscopy-based metabolomics in a dietary intervention study (n = 12). Principal component analysis (PCA) revealed a strong effect of PDX consumption on the fecal metabolome, which could be mainly ascribed to the presence of undigested fiber and oligosaccharides formed from partial degradation of PDX. Our results demonstrate that NMR-based metabolomics is a useful technique for metabolite profiling of feces and for testing compliance to dietary fiber intake in such trials. In addition, novel associations between PDX and the levels of the fecal metabolites acetate and propionate could be identified. The establishment of a correlation between the fecal metabolome and levels of Bifidobacterium (R2 = 0.66) and Bacteroides (R2 = 0.46) demonstrates the potential of NMR-based metabolomics to elucidate metabolic activity of bacteria in the gut.