Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Identification of critical residues in the active site of porcine membrane-bound aminopeptidase P

The membrane-bound form of mammalian aminopeptidase P (AP-P; EC 3.4. 11.9) is a mono-zinc-containing enzyme that lacks any of the typical metal binding motifs found in other zinc metalloproteases. To identify residues involved in metal binding and catalysis, sequence and structural information was used to align the sequence of porcine membrane-bound AP-P with other members of the peptidase clan MG, including Escherichia coli AP-P and methionyl aminopeptidases. Residues predicted to be critical for activity were mutated and the resultant proteins were expressed in COS-1 cells. Immunoelectrophoretic blot analysis was used to compare the levels of expression of the mutant proteins, and their ability to hydrolyze bradykinin and Gly-Pro-hydroxyPro was assessed. Asp449, Asp460, His523, Glu554, and Glu568 are predicted to serve as metal ion ligands in the active site, and mutagenesis of these residues resulted in fully glycosylated proteins that were catalytically inactive. Mutation of His429 and His532 also resulted in catalytically inactive proteins, and these residues, by analogy with E. coli AP-P, are likely to play a role in shuttling protons during catalysis. These studies indicate that mammalian membrane-bound AP-P has an active-site configuration similar to that of other members of the peptidase clan MG, which is compatible with either a dual metal ion model or a single metal ion in the active site. The latter model is consistent, however, with the known metal stoichiometry of both the membrane-bound and cytosolic forms of AP-P and with a recently proposed model for methionyl aminopeptidase.

Lessons from real estate partnerships in the UK: Drivers, barriers and critical success factors

Purpose – This paper seeks to summarise the main research findings from a detailed, qualitative set of structured interviews and case studies of Real Estate Partnership (REP) schemes in the UK, which involve the construction of built facilities. The research, which was funded by the Foundation for the Built Environment, examines the evolution of REPs in the UK and in Europe. The paper also aims to analyse best practice, critical factors for success, and lessons for the future. Design/methodology/approach – The research in this paper is based around ten semi-structured interviews conducted with senior representatives from corporate occupiers, property consultants, legal practices and REP service providers. Findings – The research in the paper demonstrates that REPs are particularly suited to the UK, where lease lengths are relatively long, and the level of corporate real estate owner-occupation is often higher than elsewhere. It also shows that further research is needed to examine the future shape and form of the UK REP market. Research limitations/implications – The paper is based on a limited number of in-depth case study interviews. The paper shows that further research is needed to find better ways to examine REPs empirically. Practical implications – The paper is important in highlighting a number of main issues in developing REPs: identifying with occupier's objectives; risk transfer and size of contract; and developing appropriate innovation and skills. Originality/value – The paper examines the drivers, barriers and critical success factors (at strategic and operational levels) for REPs in the UK in detail and will be of value to property managers, facilities managers, investors, financiers, and others involved in the REP process.

An intronic G run within HIV-1 intron 2 is critical for splicing regulation of vif mRNA

Within target T lymphocytes, human immunodeficiency virus type I (HIV-1) encounters the retroviral restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; A3G), which is counteracted by the HIV-1 accessory protein Vif. Vif is encoded by intron-containing viral RNAs that are generated by splicing at 3' splice site (3'ss) A1 but lack splicing at 5'ss D2, which results in the retention of a large downstream intron. Hence, the extents of activation of 3'ss A1 and repression of D2, respectively, determine the levels of vif mRNA and thus the ability to evade A3G-mediated antiviral effects. The use of 3'ss A1 can be enhanced or repressed by splicing regulatory elements that control the recognition of downstream 5'ss D2. Here we show that an intronic G run (G(I2)-1) represses the use of a second 5'ss, termed D2b, that is embedded within intron 2 and, as determined by RNA deep-sequencing analysis, is normally inefficiently used. Mutations of G(I2)-1 and activation of D2b led to the generation of transcripts coding for Gp41 and Rev protein isoforms but primarily led to considerable upregulation of vif mRNA expression. We further demonstrate, however, that higher levels of Vif protein are actually detrimental to viral replication in A3G-expressing T cell lines but not in A3G-deficient cells. These observations suggest that an appropriate ratio of Vif-to-A3G protein levels is required for optimal virus replication and that part of Vif level regulation is effected by the novel G run identified here.

Beyond description to pattern: The contribution of Batesonian epistemology to critical realist research

This paper proposes a limitation to epistemological claims to theory building prevalent in critical realist research. While accepting the basic ontological and epistemological positions of the perspective as developed by Roy Bhaskar, it is argued that application in social science has relied on sociological concepts to explain the underlying generative mechanisms, and that in many cases this has been subject to the effects of an anthropocentric constraint. A novel contribution to critical realist research comes from the work and ideas of Gregory Bateson. This is in service of two central goals of critical realism, namely an abductive route to theory building and a commitment to interdisciplinarity. Five aspects of Bateson’s epistemology are introduced: (1) difference, (2) logical levels of abstraction, (3) recursive causal loops, (4) the logic of metaphor, and (5) Bateson’s theory of mind. The comparison between Bateson and Bhaskar’s ideas is seen as a form of double description, illustrative of the point being raised. The paper concludes with an appeal to critical realists to start exploring the writing and outlook of Bateson himself.

Striatum brain-derived neurotrophic factor levels are decreased in dystrophin-deficient mice

Brain dystrophin is enriched in the postsynaptic densities of pyramidal neurons specialized regions of the subsynaptic cytoskeletal network, which are critical for synaptic transmission and plasticity. Lack of dystrophin in brain structures have been involved with impaired cognitive functions. The brain-derived neurotrophic factor (BDNF) is a regulator of neuronal survival, fast synaptic transmission, and activity-dependent synaptic plasticity. The present study investigated BDNF protein levels by Elisa analysis in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx (n = 5) and normal C57BL10 mouse (n = 5). We observed that the mdx mouse display diminution in BDNF levels in striatum (t = 6.073; df = 6; p = 0.001), while a tendency of decrease in BDNF levels was observed in the prefrontal cortex region (t = 1.962; df = 6; p = 0.096). The cerebellum (t = 1.258; df = 7; p = 0.249), hippocampus (t = 0.631; df = 7; p = 0.548) and cortex (t = 0.572; df = 7; p = 0.586) showed no significant alterations as compared to wt mouse. In conclusion, we demonstrate that only striatum decreased BDNF levels compared with wild-type (wt) mouse, differently to the other areas of the brain. This dystrophin deficiency may be affecting BDNF levels in striatum and contributing, in part, in memory storage and restoring. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Urinary 6-Sulphatoxymelatonin Levels Are Depressed in Chronic Migraine and Several Comorbidities

Objective.- To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. Background.- Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. Methods.- Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. Results.- A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. Conclusions.- To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Thioredoxin-1 promotes survival in cells exposed to S-nitrosoglutathione: Correlation with reduction of intracellular levels of nitrosothiols and up-regulation of the ERK1/2 MAP Kinases

Accumulating evidence indicates that post-translational protein modifications by nitric oxide and its derived species are critical effectors of redox signaling in cells. These protein modifications are most likely controlled by intracellular reductants. Among them, the importance of the 12 kDa dithiol protein thioredoxin-1 (TRX-1) has been increasingly recognized. However, the effects of TRX-1 in cells exposed to exogenous nitrosothiols remain little understood. We investigated the levels of intracellular nitrosothiols and survival signaling in HeLa cells over-expressing TRX-1 and exposed to S-nitrosoglutahione (GSNO). A role for TRX-1 expression on GSNO catabolism and cell viability was demonstrated by the concentration-dependent effects of GSNO on decreasing TRX-1 expression, activation of capase-3, and increasing cell death. The over-expressaion of TRX-1 in HeLa cells partially attenuated caspase-3 activation and enhanced cell viability upon GSNO treatment. This was correlated with reduction of intracellular levels of nitrosothiols and increasing levels of nitrite and nitrotyrosine. The involvement of ERK, p38 and JNK pathways were investigated in parental cells treated with GSNO. Activation of ERK1/2 MAP kinases was shown to be critical for survival signaling. lit cells over-expressing TRX-1, basal phosphorylation levels of ERK1/2 MAP kinases were higher and further increased after GSNO treatment. These results indicate that the enhanced cell viability promoted by TRX-1 correlates with its capacity to regulate the levels of intracellular nitiosothiols and to up-regulate the survival signaling pathway mediated by the ERK1/2 MAP kinases.

Transfer function-noise modeling and spatial interpolation to evaluate the risk of extreme (shallow) water-table levels in the Brazilian Cerrados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of the type of environmental stress on the emergence of sunflower (Helianthus annus L.), soybean (Glycine max (L.) Merril) and maize (Zea mays L.) seeds with different levels of vigor

Sowing is a critical time in the cycle of a crop and the seeds are frequently exposed to adverse conditions that may compromise the establishment of seedlings in the field. on this basis, the objective of the present study was to determine the effect of types of environmental stress on the emergence of sunflower, maize and soybean seeds with different levels of vigor. High vigor seeds were artificially aged in order to obtain medium and low vigor seeds and then they were sown in clay soil in plastic boxes and submitted to the following types of environmental stress during the germination process : 1) high temperature (35degreesC), 2) low temperature (15 or 18degreesC), 3) water excess (Psi > -0.0001 MPa), 4) water deficiency (Psi approximately equal to -1.1; -1.2 and -0.6 MPa for sunflower, maize and soybean, respectively), 5) sowing at a depth of 7 cm and 6) pathogenic infection of sunflower seeds with Alternaria helianthi, of maize seeds with Fusarium moniliforme and of soybean seeds with Colletotrichum dematium, var. truncata. The results were compared to those obtained with controls sown under optimal condition. It was concluded that: 1) the effect of seed vigor on emergence depends on the type of enviromental stress to which the seeds are exposed, 2) the stress to which the the seeds demonstrated highest sensitivity varied with species and 3) high temperature stress was the one that most impaired the emergence of the three species.

Productive and reproductive performance of heifers fed different levels of urea in the diet

The objective of the present study was to evaluate the nutrient intake, blood parameters, follicular diameter and performance of pre-puberty crossbred heifers fed isoproteic diets (14.1%CP) containing 0.0; 0.44; 0.88 and 1.32% urea on the total dry matter (DM) of the diet, with a 77:23 roughage:concentrate ratio. Twenty-four 18- month old heifers (Holstein x Zebu), 277.9 kg mean live weight (LW) were used, distributed in four treatments and six replications in a randomized complete design. The following were evaluated: dry matter intake (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), ether extract (EE), hemicellulose (HEM), plasmatic ureic nitrogen (PUN), plasmatic glucose, plasmatic total cholesterol, follicular diameter and daily weight gain (DWG). No influence of the urea levels in the diet was observed on NDF and HEM intake. A maximum intake was obtained of DM (8.75 kg day(-1)), CP (0.88 kg day(-1)), ADF (2.5 kg day(-1)) and EE (0.17 kg day(-1)) respectively for the levels 0.7, 0.8, 0.7 and 0.7% urea in total DM. The 0.6%; 0.77% and 0.6% urea levels in diet were the critical points for obtaining maximum response for the PUN (10.96 mg dL(-1)) and plasmatic glucose (84.97 mg dL(-1)) concentrations and, for follicular diameter (11.08 mm) on the 40(th); 24(th) and 31(st) day, respectively. The plasmatic total cholesterol concentration and DWG were not influenced by the urea added to the diet, with averages of 119.39 mg dL(-1) and 1.66 kg day(-1), respectively. It was concluded that urea can be added up to 1.32% on the total DM of the diet for pre-puberty crossbred heifers.

Bone mineralization among male adolescents: Critical years for bone mass gain

Objective: To verify the behavior of the mineral bone content and density in male adolescents according to age and secondary sexual characters. Methods: 47 healthy adolescents between 10 and 19 years old were assessed according to weight, height, body mass index, puberty stage, calcium intake, bone mineral density and content in the lumbar spine and in the proximal femur. The bone mass was measured through bone densitometries. The intake of calcium was calculated through a 3-day diet. The BMI (body mass index) was calculated with the Quetelet Index and the puberty stage was defined according to Tanner's criteria. The analysis used descriptive statistics such as average and standard deviation, and variance estimates to compare the different age groups. Moreover, the Tukey test was used to determine the significant differences. Results: It was evident that the calcium intake in the different ages assessed has not reached the minimum value of 800 mg. The bone mineral density and content showed an increase after the age of 14, as well as when the teenagers reached the sexual maturation stage G4. The mineralization parameters showed a high level when the teenagers were in the G3 stage, however, without statistical significance. Conclusion: The results indicate an important level of bone mineralization during adolescence. Maturation levels superior to G3 have shown more mineralization. This study proves that the critical years for bone mass gain start after the 14-15 years old or older. Copyright © 2004 by Sociedade Brasileira de Pediatria.

Effects of gender on stroke rates, critical speed and velocity of a 30-min swim in young swimmers

Our objective was to analyze the effect of gender on the relationship between stroke rates corresponding to critical speed (SRCS) and maximal speed of 30 min (SRS30) in young swimmers. Twenty two males (GM1) (Age = 15.4 ± 2.1 yr., Body mass = 63.7 ± 12.9 kg, Stature = 1.73 ± 0.09 m) and fourteen female (GF) swimmers (Age = 15.1 ± 1.6 yr., Body mass = 58.3 ± 8.8 kg, Stature = 1.65 ± 0.06 m) were studied. A subset of males (GM2) was matched to the GF by their velocity for a 30 min swim (S30). The critical speed (CS) was determined through the slope of the linear regression line between the distances (200 and 400 m) and participant's respective times. CS was significantly higher than S30 in males (GM1 - 1.25 and 1.16 and GM2 - 1.21 and 1.12 m·s-1) and females (GF - 1.15 and 1.11 m·s-1). There was no significant difference between SRCS and SRS30 in males (GM1 - 34.16 and 32.32 and GM2 - 34.67 and 32.46 cycle·s-1, respectively) and females (GF - 34.18 and 33.67 cycle·s-1-1, respectively). There was a significant correlation between CS and S30 (GM1 - r = 0.89, GF - r = 0.94 and GM2 - r = 0.90) and between SRCS and SRS30 (GM1 - r = 0.89, GF - r = 0.80 and GM2 - r = 0.88). Thus, the relationship between SRCS and SRS30 is not influenced by gender, in swimmers with similar and different aerobic capacity levels. ©Journal of Sports Science and Medicine (2007).

Elevated Plasma Hemoglobin Levels Increase Nitric Oxide Consumption in Experimental and Clinical Acute Pulmonary Thromboembolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)