Blood pressure lowering effects of Lactobacillus helveticus fermented milk containing bioactive peptides Ile-Pro-Pro and Val-Pro-Pro; mechanistic, kinetic and clinical studies

The purpose of the present study was to evaluate the effects of Lactobacillus helveticus fermented milk (peptide milk) containing the casein-derived tripeptides Isoleucyl-prolyl-proline (Ile-Pro-Pro) and Valyl-prolyl-proline (Val-Pro-Pro) on blood pressure and vascular function in hypertensive subjects. The peptide milk lowered systolic and diastolic blood pressure in long-term use in hypertensive subjects when blood pressure was measured by using 24-hour ambulatory blood pressure measurement (ABPM). The blood pressure lowering effect was seen with the dose of 50 mg of tripeptides, and a tendency for lowering blood pressure was also observed when the dose was 5 mg. No adverse effects compared to the placebo group were reported or detected in laboratory analysis. The effect of the peptide milk on arterial stiffness was shown using two different methods, the ambulatory arterial stiffness index (AASI) and pulse wave analysis (PWA). According to the AASI, arterial stiffness was significantly reduced in the peptide milk group compared to the baseline level, but the difference was not significant compared to the placebo group. PWA showed that the peptide milk reduced arterial stiffness significantly compared to the placebo group. Endothelium-independent relaxation (nitroglycerin) and endothelium-dependent relaxation (salbutamol) did not differ between the groups. The blood pressure lowering mechanisms of the tripeptides and the kinetics of Ile-Pro-Pro were investigated using spontaneously hypertensive rats (SHR) and Sprague-Dawley rats. Previous studies have suggested that the blood pressure lowering effect of the tripeptides Ile-Pro-Pro and Val-Pro-Pro is based on angiotensin-converting enzyme inhibition, but the present findings did not agree with these previous studies. It was shown in SHR that calcium, potassium and magnesium may also have an important role in attenuating the development of hypertension as part of the peptide milk effect. In addition, the present study suggests indirectly that improved endothelial nitric oxide release capacity is not the mechanism by which peptide milk mediates its favourable circulatory effects. The kinetics of Ile-Pro-Pro were studied using adult Sprague-Dawley rats. The results showed that orally administered Ile-Pro-Pro is absorbed at least partly intact from the gastrointestinal tract. Radiolabelled Ile-Pro-Pro was distributed in different tissues and considerable radioactivity levels were found in tissues related to the renin-angiotensin system (RAS), adrenals, aorta and kidneys. Ile-Pro-Pro does not bind to plasma proteins, and therefore it is possible that its blood pressure lowering effect is mediated by free Ile-Pro-Pro. In conclusion, consumption of the peptide milk lowers blood pressure and reduces arterial stiffness in hypertensive subjects. Ile-Pro-Pro can be absorbed partly intact from the gastrointestinal tract and might accumulate in tissues related to the RAS. The precise blood pressure lowering mechanism of peptide milk remains to be studied.

Metallization and crystallization of semiconducting amorphous Ga20Te80 alloy under high pressure

Pressure and temperature dependence of the electrical resistivity of amorphous Ga20Te80 alloy is reported for the first time. The alloy undergoes a pressure induced amorphous semiconductor-to-crystalline metal phase transition at 6.5 ± 0.5 GPa. The high pressure crystalline phase is a mixture of Te and GaTe3 phases.

Pressure-induced electronic and structural transformations in bulk gese2 glass

The pressure dependence of the electrical of the electrical resistivity of bulk GeSe2 glass shows a semiconductor-to-metal transition at 7 GPa pressure. The high pressure phase is examined using he x-ray diffractometer and is found to be crystalline, with a face-centered cubic structure having a =4.06A. The electrical conductivity has also been studied as a function of temperature at various pressures.

Milk casein-derived tripeptides : A special focus on blood pressure and vascular function

Increased consumption of low-fat milk products is inversely associated with the risk of hypertension. The beneficial effect of milk on blood pressure is attributed to high calcium and potassium content but also to specific peptide sequences, which are cleaved from milk protein during gastrointestinal digestion, fermentation of milk with proteolytic starter cultures or enzymatic hydrolysis. Milk products fermented with Lactobacillus helveticus contain casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro), which have been shown to possess antihypertensive effects in humans and in experimental animals. The aim of the present series of studies was to investigate the effects of tripeptides Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them on vascular function and blood pressure and to elucidate the mechanisms behind them by using different experimental models of hypertension. Another aim was to characterize the acute effects of tripeptides on blood pressure and arterial stiffness in mildly hypertensive humans. Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them attenuated the development of hypertension in two experimental models of hypertension, spontaneously hypertensive rat (SHR) and type 2 diabetic Goto-Kakizaki (GK) rat fed with high-salt diet. Significant differences in systolic blood pressure (SBP) were seen after 8 weeks treatment with tripeptide-containing products compared to control product. Plant sterols did not enhance this effect. Two differently produced tripeptide powders produced a similar attenuating effect on SBP in SHR. In mildly hypertensive subjects, a single administration of tripeptide- and plant sterol-containing fermented milk product decreased both SBP and diastolic blood pressure (DBP) over a period of 8 hours. Protective effect of tripeptides Ile-Pro-Pro and Val-Pro-Pro and fermented milk products containing them on vascular function was demonstrated in in vitro studies and long-term experimental studies. The effect was shown to be endothelium-dependent and possibly involving endothelium-derived hyperpolarizing factor (EDHF). In the clinical study, single administration of tripeptide-containing fermented milk product did not affect measures of arterial stiffness. Long-term treatment with fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro inhibited angiotensin-converting enzyme (ACE) and decreased aldosterone levels thus showing beneficial effects on the renin-angiotensin system (RAS) in SHR and GK. No changes in the components of RAS were observed by the single administration of the same product in mildly hypertensive subjects. Increased levels of cGMP, NOx and citrulline suggest increased nitric oxide (NO) production by the tripeptides. Taken together, Ile-Pro-Pro and Val-Pro-Pro -containing products attenuate the development of hypertension after long-term treatment in experimental models of hypertension and possess an acute antihypertensive effect in mildly hypertensive subjects. In addition, these tripeptides show endothelium-mediated beneficial effects on vascular function. Attenuation of blood pressure increase by the tripeptides in experimental animals involves RAS, but its role in the antihypertensive effect in humans remains to be elucidated.

High pressure induced crystallization of rapidly solidified Al---Fe and Al---Mn quasi-crystalline alloysstar

The presence of phases showing icosahedral point symmetry was reported by Shechtman, Blech, Gratias and Cahn in rapidly quenched alloys of Al---Mn, Al---Fe and Al---Cr, and subsequently many other splat-cooled alloys with the i phase have been reported. In this paper we present the first results of high pressure experiments carried out on Al---Fe and Al---Mn quasi-crystals. The experiments performed at room temperature showed irreversible quasi-crystal-to-crystal transitions in Al---Mn and Al---Fe alloys. The transition pressures are 49 kbar for Al78Mn22, 93 kbar for Al86Mn14, 79 kbar for Al86Fe14, 54 kbar for Al82Fe18 and 108 kbar for Al75Fe25. The high pressure phases are found to be the equilibrium phases.

Molecular Mechanisms of Androgen Receptor Interactions

The androgen receptor (AR) mediates the effects of the male sex-steroid hormones (androgens), testosterone and 5?-dihydrotestosterone. Androgens are critical in the development and maintenance of male sexual characteristics. AR is a member of the steroid receptor ligand-inducible transcription factor family. The steroid receptor family is a subgroup of the nuclear receptor superfamily that also includes receptors for the active forms of vitamin A, vitamin D3, and thyroid hormones. Like all nuclear receptors, AR has a conserved modular structure consisting of a non-conserved amino-terminal domain (NTD), containing the intrinsic activation function 1, a highly conserved DNA-binding domain, and a conserved ligand-binding domain (LBD) that harbors the activation function 2. Each of these domains plays an important role in receptor function and signaling, either via intra- and inter-receptor interactions, interactions with specific DNA sequences, termed hormone response elements, or via functional interactions with domain-specific proteins, termed coregulators (coactivators and corepressors). Upon binding androgens, AR acquires a new conformational state, translocates to the nucleus, binds to androgen response elements, homodimerizes and recruits sequence-specific coregulatory factors and the basal transcription machinery. This set of events is required to activate gene transcription (expression). Gene transcription is a strictly modulated process that governs cell growth, cell homeostasis, cell function and cell death. Disruptions of AR transcriptional activity caused by receptor mutations and/or altered coregulator interactions are linked to a wide spectrum of androgen insensitivity syndromes, and to the pathogenesis of prostate cancer (CaP). The treatment of CaP usually involves androgen depletion therapy (ADT). ADT achieves significant clinical responses during the early stages of the disease. However, under the selective pressure of androgen withdrawal, androgen-dependent CaP can progress to an androgen-independent CaP. Androgen-independent CaP is invariably a more aggressive and untreatable form of the disease. Advancing our understanding of the molecular mechanisms behind the switch in androgen-dependency would improve our success of treating CaP and other AR related illnesses. This study evaluates how clinically identified AR mutations affect the receptor s transcriptional activity. We reveal that a potential molecular abnormality in androgen insensitivity syndrome and CaP patients is caused by disruptions of the important intra-receptor NTD/LBD interaction. We demonstrate that the same AR LBD mutations can also disrupt the recruitment of the p160 coactivator protein GRIP1. Our investigations reveal that 30% of patients with advanced, untreated local CaP have somatic mutations that may lead to increases in AR activity. We report that somatic mutations that activate AR may lead to early relapse in ADT. Our results demonstrate that the types of ADT a CaP patient receives may cause a clustering of mutations to a particular region of the receptor. Furthermore, the mutations that arise before and during ADT do not always result in a receptor that is more active, indicating that coregulator interactions play a pivotal role in the progression of androgen-independent CaP. To improve CaP therapy, it is necessary to identify critical coregulators of AR. We screened a HeLa cell cDNA library and identified small carboxyl-terminal domain phosphatase 2 (SCP2). SCP2 is a protein phosphatase that directly interacts with the AR NTD and represses AR activity. We demonstrated that reducing the endogenous cellular levels of SCP2 causes more AR to load on to the prostate specific antigen (PSA) gene promoter and enhancer regions. Additionally, under the same conditions, more RNA polymerase II was recruited to the PSA promoter region and overall there was an increase in androgen-dependent transcription of the PSA gene, revealing that SCP2 could play a role in the pathogenesis of CaP.

Electrical transport in layered crystalline semiconductors GeS doped with Ag, P impurities at high pressure

A study of the transport properties of layered crystalline semiconductors GeS (undoped and doped with Ag, P impurity) under quasihydrostatic pressure using Bridgman anvil system is made for the first time. Pressure-induced effects in undoped crystals reveal initial rise in resistivity followed by two broad peaks at higher pressures. Silver doping induces only minor changes in the behaviour except removing the second peak. Phosphorous impurity is found to have drastic effect on the transport properties. Temperature dependence of the resistivity exhibits two activation energies having opposite pressure coefficients. Results are discussed in the light of intrinsic features of the layered semiconductors.

Pressure induced effects in bulk amorphous n-type semiconductors(GeSe3.5)100âxBix

The effect of pressure on the electrical resistivity of amorphous n-type (GeSe3.5)100�xBix been studied in a Bridgeman anvil system up to a pressure of 90 kbar down to liquid nitrogen temperature. A continuous amorphous semiconductor to metal-like solid transition in the undoped GeSe3.5 is observed at room temperature. Incorporation of Bi in the GeSe3.5 network is found to significantly disturb the behaviour of the resistivity with pressure. With increasing Bi concentration a much broader variation in resistivity with pressure is observed. The temperature dependence of the resistivity and activation energy at different pressures is also measured and they are found to be composition dependent. Results are discussed in the light of the Phillips Model of ordered clusters in chalcogenide semiconductors.

Generation of rotationally dominated galaxies by mergers of pressure-supported progenitors

Through the analysis of a set of numerical simulations of major mergers between initially non-rotating, pressure-supported progenitor galaxies with a range of central mass concentrations, we have shown that: (1) it is possible to generate elliptical-like galaxies, with outside one effective radius, as a result of the conversion of orbital- into internal-angular momentum; (2) the outer regions acquire part of the angular momentum first; (3) both the baryonic and the dark matter components of the remnant galaxy acquire part of the angular momentum, the relative fractions depending on the initial concentration of the merging galaxies. For this conversion to occur the initial baryonic component must be sufficiently dense and/or the encounter should take place on an orbit with high angular momentum. Systems with these hybrid properties have recently been observed through a combination of stellar absorption lines and planetary nebulae for kinematic studies of early-type galaxies. Our results are in qualitative agreement with these observations and demonstrate that even mergers composed of non rotating, pressure-supported progenitor galaxies can produce early-type galaxies with significant rotation at large radii.

Defining critical soil nutrient concentrations in soils supporting grains and cotton in Northern NSW and Queensland

This project focussed on the phosphorus (P) and potassium (K) status of northern cropping soils. Stores of P and K have been depleted by crop removal and limited fertiliser application, with depletion most significant in the subsoil. Soil testing strategies are confounded by slowly available mineral reserves with uncertain availability. The utility of new soil tests was assessed to measure these reserves, their availability to plants quantified and a regional sampling strategy undertaken to identify areas of greatest P and K deficit. Fertiliser application strategies for P and K have been tested and the interactions between these and other nutrients have been determined in a large field program.

Maximising profitability with limited water in cotton farming systems

Diminishing water supply, changing weather patterns and pressure to enhance environmental flows are making it imperative to optimise water use efficiency (WUE) on cotton/grain farming systems. Growers are looking for better strategies to make the best use of limited water, but it is still not clear how to best use the available water at farm and field scale. This research project investigated the impact of management strategies to deal with limited water supplies on the yield and quality of irrigated cotton and wheat. The objectives were: (1) to develop irrigation management guidelines for the main irrigated crops on the Darling Downs for full- and deficitirrigation scenarios, taking into account the critical factors that affect irrigation decisions at the local level, (2) to quantify the evapotranspiration (ET) of Bollgard II cotton and wheat and its relationship to yield and quality under full- and deficit-irrigation scenarios, and (3) to increase industry awareness and education of farming systems practises for optimised economic water use efficiency.Objective (1) was addressed by (A) collaborating with ASPRU to develop the APSFarm model within APSIM to be able to perform multi-paddock simulations. APSFarm was then tested by conducting a case study at a farm near Dalby, and (B) conducting semi-structured interviews with individual farmers and crop consultants on the Darling Downs to document the strategies they are using to deal with limited water. Objective (2) was addressed by (A) building and installing 12 large (1 m x 1m x 1.5 m) weighing lysimeters to measure crop evapotranspiration. The lysimeters were installed at the Agri-Science Queensland research station at Kingsthorpe in November 2008, (B) conducting field experiments to measure crop evapotranspiration and crop development under four irrigation treatments, including dryland, deficit-irrigation, and full irrigation. Field experiments were conducted with cotton in 2007-08 and 2008-09, and with wheat in 2008 and 2009, and (C) collaborating with USQ on a PhD thesis to quantify the impact of crop stress on crop evapotranspiration and canopy temperature. Glasshouse experiments were conducted with wheat in 2008 and with cotton in 2008-09. Objective (3) was addressed by (A) conducting a field day at Kingsthorpe in 2009, which was attended by 80 participants, (B) presenting information in conferences in Australia and overseas, (D) presenting information at farmers meeting, (E) making presentations to crop consultants, and (F) preparing extension publications.As part of this project we contributed to the development of APSfarm, which has been successfully applied to evaluate the feasibility of practices at the whole-farm scale. From growers and crop consultants interviews we learned that there is a great variety of strategies, at different scales, that they are using to deal with limited water situation. These strategies will be summarised in the "e;Limited Water Guidelines for the Darling Downs"e; that we are currently preparing. As a result of this project, we now have a state-of-the-art lysimeter research facility (23 large weighing lysimeters) to be able to conduct replicated experiments to investigate daily water use of a variety of crops under different irrigation regimes and under different environments. Under this project, a series of field and glasshouse experiments were conducted with cotton and wheat, investigating aspects like: (A) quantification of daily and seasonal crop water use under nonstressed and stressed conditions, (B) impact of row configuration on crop water use, (C) impact of water stress on yield, evapotranspiration, crop vegetative and reproductive development, soil water extraction pattern, yield and yield quality. The information obtained from this project is now being used to develop web-based tools to help growers make planning and day-to-day irrigation decisions.

Study of effects of dopants on structure of vitreous semiconductors (GeSe3.5)100-xMx (M = Bi, Sb) using high pressure techniques

An investigation of the problem of controlled doping of amorphous chalcogenide semiconductors utilizing a Bridgman anvil high pressure technique, has been undertaken. Bulk amorphous semiconducting materials (GeSe3.5)100-x doped with M = Bi (x = 2, 4, 10) and M = Sb (x = 10) respectively are studied up to a pressure of 100 kbar down to liquid nitrogen temperature, with a view to observe the impurity induced modifications. Measurement of the electrical conductivity of the doped samples under quasi-hydrostatic pressure reveals that the pressure induced effects in lightly doped (2 at % Bi) and heavily doped (x = 4, 10) semiconductors are markedly different. The pressure effects in Sb-doped semiconductors are quite different from those in Bi-doped material.

Discussion of enthalpy, entropy and free energy of formation of GaN

Presented in this letter is a critical discussion of a recent paper on experimental investigation of the enthalpy, entropy and free energy of formation of gallium nitride (GaN) published in this journal [T.J. Peshek, J.C. Angus, K. Kash, J. Cryst. Growth 311 (2008) 185-189]. It is shown that the experimental technique employed detects neither the equilibrium partial pressure of N-2 corresponding to the equilibrium between Ga and GaN at fixed temperatures nor the equilibrium temperature at constant pressure of N-2. The results of Peshek et al. are discussed in the light of other information on the Gibbs energy of formation available in the literature. Entropy of GaN is derived from heat-capacity measurements. Based on a critical analysis of all thermodynamic information now available, a set of optimized parameters is identified and a table of thermodynamic data for GaN developed from 298.15 to 1400 K.