Methionine regulates copper/hydrogen peroxide oxidation products of Aβ

Metal-catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid peptide (A), the major biomarker of AD, in the presence of copper ions reduces Cu2+ to Cu+ and catalyses the formation of H2O2 that subsequently induces radicals through Fenton chemistry. A is also subject to attack by free radicals, where the presence of Cu2+ in conjunction with H2O2 catalyses oxygenation, primarily at the methionine sulfur atom. This work investigates MCO of A, to gain further insight into the role of oxidative stress in AD. By combining a fluorescence assay with gel electrophoresis to monitor MCO reactions of A (1-28) in the presence and absence of methionine it was determined that methionine can both protect some residues against MCO and promote the oxidation of Tyr(10) specifically. Electrospray ionization mass spectrometric analysis of methionine MCO products indicated the formation of methionine sulfoxide, methionine sulfone and related hydroxylated products. Similar products could be formed from the oxidation of Met(35) of A and may relate to changes in properties of the peptide following MCO.

Just 'good and bad news'? Disciplinary imaginaries of head teachers in Australian and English print media

Australian and English print media are actively engaged in producing reports that claim to find the 'best schools', the 'real state of education', and 'star head teachers'. This article considers the production of knights and dames, maverick heads and struggling schools. It argues that some of these stories are clearly the products of departmental press bureau activities and policy agendas. It shows, however, that even those stories intended to critique government policy support paradoxically a notion of the singular importance of the headship and the virtues of heroic leadership. It is suggested that the simulacrum of the heroic head works as a normative disciplinary device for performative and market practices and is singularly off-putting to both serving and aspirant school leaders.

Defuturing an architecture of destruction: a reconciliation of Van Berkel and Bos to the new design philosophy of Tony Fry

For some time now Tony Fry has promoted the idea of 'The Sustainment', an idea that asserts a paradigm shift in attitudes to consumption. 'The Sustainment' recognises that increasingly human futures are products of self-determination and not chance. Fry’s hypothesis can be understood through his concept of Defuturing, a philosophy that questions the role of design and the responsibility of designers to facilitating the ability to sustain (Fry 1999).
Central to Fry’s philosophy is an awareness that it is in the best interests of designers and their clients, as inhabitants of cultures increasingly driven by technology, to be aware of the relationships between the products and theories of design and the processes and implications of technological change. This is an awareness that is central to the concepts, work, and methodologies of the ‘UN Studio’ of Van Berkel and Bos described and elaborated upon in Move – Imagination, Techniques, and Effects (Van Berkel & Bos 1999). Here, Ben Van Berkel defines the parameters and methodologies employed by UN Studio in an environment of technological and socio-economic change. The Dutch practice could be said to exemplify something of a zeitgeist in current architectural design that sees architects, as Van Berkel and Bos view them, as “fashion designers of the future, dressing events to come and holding up a mirror to the world (Van Berkel & Bos 1999, back cover).” It is a zeitgeist that Fry might see as aligned to the resilient hype of ‘new creativity’, ‘globalisation’ the ‘romance with technology’, and the vacuous-ness of the world of fashion. (Fry The Voice of Sustainment: on Design Intelligence 2005).
A source of breaking down such design propaganda is identified by Fry in the notion of ‘scenarios,’ which “provide a mechanism for politico-practice assemblage in which dialogues and narratives of change can be rehearsed in ways that enable participants to re-educate themselves via critical confrontations” (Fry The Voice of Sustainment: on Design Intelligence 2005). From such a perspective this paper aims to practically illustrate and ground the Defuturing of Fry by establishing a dialogue between his writings and the theories that have generated the architectural designs of Van Berkel and Bos and there UN Studio. This will be a ‘scenario’ that examines therefore an appropriation and transformation of the applied intellectual practice of Van Berkel and Bos. Through this confrontation we shall explore the question of why sustainability appears to be so low in the agenda of many pre-eminent contemporary architects, and how we might refocus therefore practice and theory on the ability to sustain.

A role for skeletal muscle stearoyl-CoA desaturase 1 in control of thermogenesis

An enhanced metabolic efficiency for accelerating the recovery of fat mass (or catch-up fat) is a characteristic feature of body weight regulation after weight loss or growth retardation and is the outcome of an "adipose-specific" suppression of thermogenesis, i.e., a feedback control system in which signals from the depleted adipose tissue fat stores exert a suppressive effect on thermogenesis. Using a previously described rat model of semistarvation-refeeding in which catch-up fat results from suppressed thermogenesis per se, we report here that the gene expression of stearoyl-coenzyme A desaturase 1 (SCD1) is elevated in skeletal muscle after 2 wk of semistarvation and remains elevated in parallel to the phase of suppressed thermogenesis favoring catch-up fat during refeeding. These elevations in the SCD1 transcript are skeletal muscle specific and are associated with elevations in microsomal ^9 desaturase enzyme activity, in the ^9 desaturation index, and in the relative content of SCD1-derived monounsaturates in several lipid fractions extracted from skeletal muscle. An elevated skeletal muscle SCD1, by desaturating the products of de novo lipogenesis and diverting them away from mitochondrial oxidation, would inhibit substrate cycling between de novo lipogenesis and lipid oxidation, thereby leading to a state of suppressed thermogenesis that regulates the body’s fat stores.—Mainieri, D., Summermatter, S., Seydoux, J., Montani, J. P., Rusconi, S., Russell, A. P., Boss, O., Buchala, A. J., Dulloo, A. G. A role for skeletal muscle stearoyl-CoA desaturase 1 in control of thermogenesis.

Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered Thalidomide

The clinical use of irinotecan (CPT-11) is hindered by dose-limiting diarrhea and myelosuppression. Recent clinical studies indicate that thalidomide, a known tumor necrosis factor-alpha inhibitor, ameliorated the toxicities induced by CPT-11. However, the mechanisms for this are unknown. This study aimed to investigate whether combination of thalidomide modulated the toxicities of CPT-11 using a rat model and the possible role of the altered pharmacokinetic component in the toxicity modulation using in vitro models. The toxicity model was constructed by treatment of healthy rats with CPT-11 at 60 mg/kg per day by intravenous (i.v.) injection. Body weight, acute and delayed-onset diarrhea, blood cell counts, and macroscopic and microscopic intestinal damages were monitored in rats treated with CPT-11 alone or combined therapy with thalidomide at 100 mg/kg administered by intraperitoneal (i.p.) injection. Single dose and 5-day multiple-dose studies were conducted in rats to examine the effects of concomitant thalidomide on the plasma pharmacokinetics of CPT-11 and its major metabolites SN-38 and SN-38 glucuronide (SN-38G). The effect of CPT-11 on thalidomide's pharmacokinetics was also checked. Rat liver microsomes and a rat hepatoma cell line, H4-II-E cells, were used to study the in vitro metabolic interactions between these two drugs. H4-II-E cells were also used to investigate the effect of thalidomide and its hydrolytic products on the transport of CPT-11 and SN-38. In addition, the effect of thalidomide and its hydrolytic products on rat plasma protein binding of CPT-11 and SN-38 was examined. Administration of CPT-11 by i.v. for 4 consecutive days to rats induced significant body weight loss, decrease in neutrophil and lymphocyte counts, severe acute- and delayed-onset diarrhea, and intestinal damages. These toxicities were alleviated when CPT-11 was combined with thalidomide. In both single-dose and 5-day multiple-dose pharmacokinetic study, coadministered thalidomide significantly increased the area under the plasma concentration-time curve (AUC) of CPT-11, but the AUC and elimination half-life (t(1/2)) of SN-38 were significantly decreased. However, CPT-11 did not significantly alter the pharmacokinetics of thalidomide. Thalidomide at 25 and 250 microM and its hydrolytic products at a total concentration of 10 microM had no significant effect on the plasma protein binding of CPT-11 and SN-38, except for that thalidomide at 250 microM caused a significant increase in the unbound fraction (f(u)) of CPT-11 by 6.7% (P < 0.05). The hydrolytic products of thalidomide (total concentration of 10 microM), but not thalidomide, significantly decreased CPT-11 hydrolysis by 16% in rat liver microsomes (P < 0.01). The formation of both SN-38 and SN-38G from CPT-11, SN-38 glucuronidation, or intracellular accumulation of both CPT-11 and SN-38 in H4-II-E cells followed Michaelis-Menten kinetics with the one-binding site model being the best fit for the kinetic data. Coincubation or 2-hr preincubation of thalidomide at 25 microM and 250 microM and its hydrolytic products at 10 microM did not show any significant effects on CPT-11 hydrolysis and SN-38 glucuronidation. However, preincubation of H4-II-E cells with thalidomide (250 microM), its hydrolytic products (total concentration of 10 microM), or phthaloyl glutamic acid (one major thalidomide hydrolytic product, 10 microM) significantly increased the intracellular accumulation of SN-38, but not CPT-11 (P < 0.01). The dose-limiting toxicities of CPT-11 were alleviated by combination with thalidomide in rats and the pharmacokinetic modulation by thalidomide may partially explain its antagonizing effects on the toxicities of CPT-11. The hydrolytic products of thalidomide, instead of the parental drug, modulated the hepatic hydrolysis of CPT-11 and intracellular accumulation of SN-38, probably contributing to the altered plasma pharmacokinetics of CPT-11 and SN-38. Further studies are needed to explore the role of both pharmacokinetics and pharmacodynamic components in the protective effect of thalidomide against the toxicities of CPT-11.

Functional extruded snack products based on chickpea (Cicer arietinum L.) and fenugreek (Trigonella foenum-graecum) flours

Background – Chickpea and fenugreek are both legumes that confer several nutritional and functional virtues, especially to diabetes and associated metabolic syndrome conditions. They are high in protein and fibre, low in fat and prove to be low glycaemic. They also provide a gluten-free alternative to those suffering from celiac disease. Though these seeds are locally available, hardly any products appear on the supermarket shelves.
Objectives – The aim was to utilise the health and nutritional benefits of chickpea and fenugreek and develop acceptable snack products by extrusion technology.
Design – Preliminary trials were conducted with different proportions of rice and chickpea at a range of extruder conditions to optimise the raw material and processing conditions. Studies were then conducted at optimum processing conditions using a 7:3 chickpea and rice combination replacing with 2% fenugreek or 5, 10, 15 and 20% FenuLifeÒ (deodorized fenugreek powder). Products were evaluated for their physical (expansion, crunchiness and colour) and sensory ( texture, colour, flavour and overall acceptability) characteristics in order to identify their suitability as snack products.
Outcomes – Addition of chickpea up to 70% with rice showed increased expansion and stable product characteristics. Addition of fenugreek and FenuLifeÒ, indicated slight reduction in product expansion (radial) and crunchiness. However, the product made with 20% FenuLifeÒ had significant changes in expansion, crunchiness and colour values. The median scores of sensory evaluation indicated that all products were within the acceptable range. Inclusion of fenugreek showed lower ratings for flavour due to the strong bitter taste of fenugreek. There were no significant differences between products containing FenuLifeÒ (5-15%) in their colour, flavour, texture and overall quality.
Conclusion – This study demonstrates an opportunity for using chickpea and fenugreek in functional product development. Fenugreek in the form of deodorize powder (fenulifeÒ) could be incorporated up to 15% in a mixture of chickpea and rice to develop snack products of acceptable physical and sensory properties.

Properties of mechanically milled and spark plasma sintered Al–15 at.% MgB2 composite materials

Air-atomized pure aluminium powder with 15 at.% MgB₂ was mechanically milled (MMed) by using a vibrational ball mill, and MMed powders were consolidated by spark plasma sintering (SPS) to produce composite materials with high specific strength. Solid-state reactions of MMed powders have been examined by X-ray diffraction (XRD), and mechanical properties of the SPSed materials have been evaluated by hardness measurements and compression tests. Orientation images of microstructures were obtained via the electron backscatter diffraction (EBSD) technique.

The solid-state reactions in the Al–15 at.% MgB₂ composite materials occurred between the MMed powders and process control agent (PCA) after heating at 773–873 K for 24 h. The products of the solid-state reaction were a combination of AlB₂, Al₃BC and spinel MgAl₂O₄. Mechanical milling (MM) processing time and heating temperatures affect the characteristics of those intermetallic compounds. As the result of the solid-state reactions in MMed powders, a hardness increase was observed in MMed powders after heating at 573–873 K for 24 h. The full density was attained for the SPSed materials from 4 h or 8 h MMed powders in the Al–15 at.% MgB₂ composite materials under an applied pressure of 49 MPa at 873 K for 1 h. The microstructure of the SPSed materials fabricated from the MMed powders presented the bimodal aluminium matrix grain structure with the randomly distributions. The Al–15 at.% MgB₂SPSed material from powder MMed for 8 h exhibited the highest compressive 0.2% proof strength of 846 MPa at room temperature.

Extruded products with Fenugreek (Trigonella foenum-graecium) chickpea and rice: Physical properties, sensory acceptability and glycaemic index

The present study investigated the effects of fenugreek flour (Trigonella foenum-graecum) and debittered fenugreek polysaccharide (FenuLife^®) inclusion on the physical and sensory quality characteristics, and glycaemic index (GI) of chickpea–rice based extruded products. Based on preliminary evaluation with different proportions of chick pea and rice, a blend of 70:30 chickpea and rice was chosen as the control for further studies. The control blend, replaced with fenugreek flour at 2%, 5% and 10%, or fenugreek polysaccharide at 5%, 10%, 15% and 20%, was extruded at the optimum processing conditions as specified in the detailed study. The extruded products were evaluated for their physical (moisture retention, expansion, hardness, water solubility index (WSI) and water absorption index (WAI)), sensory (flavor, texture, color and overall acceptability) characteristics and in vitro GI to evaluate their suitability as extruded snack products.

Due to the distinct bitter taste, inclusion of fenugreek flour was not acceptable at levels more than 2% in extruded chickpea based products. Addition of fenugreek polysaccharide resulted in slight reduction in radial expansion (P < 0.05), while longitudinal expansion increased. WAI increased while WSI decreased compared to the control (P < 0.05). The mean scores of sensory evaluation indicated that all products containing fenugreek polysaccharide up to 15% were within the acceptable range. There were no significant differences (P > 0.05) between products containing 5–15% fenugreek polysaccharide in their color, flavor, texture and overall quality.

Fenugreek, in the form of debittered polysaccharide (FenuLife^®) could be incorporated up to a level of 15% in a chickpea–rice blend to develop snack products of acceptable physical and sensory properties with low GI Index.

Life and death : metabolic rate, membrane composition, and life span of animals

Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.

A quantitative approach to analysing reliability of engagement responses to dance

Perhaps one of the most important end products of a dance work is how it  effects its observers (typically its audience, but also the dancers and choreographers). Of the many ways of discussing and analysing dance, one
approach in its infancy is quantification. Our research involves combining continuous response techniques and human response methods to see if we can tease out relationships between continuous, quantitative evaluative responses and the more qualitative choreographer intentions. The aim of this paper is to describe how evaluative responses can be quantified at all, then how they can be related to an unfolding dance work, and finally, how we can isolate ‘meaningful’ or ‘significant’ or ‘reliable’ evaluations of a dance work from those which are no more than a spurious set of not-very-useful numbers presented under the guise of a valid assessment.

Does the inclusion of moderate amounts of red meat in the diet of exercising older women impact on faecal markers of bowel health, including faecal lactoferrin?

Background: High intakes of red meat may be associated with increased risk of colorectal cancer (CRC), however, to determine CRC risk, it is important to assess faecal changes related to protein and carbohydrate metabolism.

Objective: To determine the influence of three weekly meals rich in red meat as opposed to a carbohydrate control diet on faecal markers which are involved in the aetiology of CRC.

Design: Twenty post-menopausal women (aged 60-75) undertook, 3 times a week for 12 weeks, a 30 minute exercise session followed immediately by a cooked meal that was high in lean red meat, low in carbohydrate (n= 10) or low in lean red meat, high in carbohydrate (n=10). Dietary fibre intake and macronutrients were kept constant. At the beginning and end of the study, three-day faecal samples were collected and by-products of protein fermentation and carbohydrate metabolism, undigested fibre residues, and faecal output and colonic bacterial microbiota changes measured.

Outcomes: No significant differences were observed in subjects on either diet when comparing faecal output, faecal pH, other faecal markers, nor faecal lactoferrin. There was a trend observed in changes in the population of colonic microbiota using FISH analysis. Bacteroides spp. and Prevotella spp. appeared to decrease in women consuming a high red meat diet compared with an increase in women consuming a high carbohydrate diet.

Conclusions: In this pilot study the trend in colonic microbiota change is interesting and suggests that dietary influence of colonic microbiota, especially changes in Bacteroidetes, may be indicative of risk of gut damage and disease compared to other faecal markers.

Contentless thought : case study in the meaninglessness of all views

To defeat the heirs of the enlightenment with their own weapon i.e. reason itself. To reduce all philosophy all science all views to irrational meaningless babble using their own epistemic conditions of truth. To confound the products of reason by reason itself. To show that the rational in fact collapses into the irrational. By reason itself all products of human reason reduce to intellectual chaos. To shatter the categories of thought, to rob all views and ideas of any epistemic worth by using reason to show that they end in stultification foolishness, or absurdity. Reason confounds reason and convicts reason by it's own standard to unintelligibility, babble, stultification, incoherence foolishness and absurdity, or meaninglessness. Reasons critique of reason shows that there is no consistency in ally product of reason, no order , no coherence only chaos and absurdity, or meaninglessness. The life-jacket, or anchor reason gives in the void of meaninglessness is broken by reason itself. Into the void of nothing reason drops us. Cut adrift in meaninglessness we are free to acquire other insights other realizations by transcending reason. Meaning can be reduced to absurdity. Meaninglessness can be reduced to absurdity but for those who hold meaninglessness as a view, or meaning there is no hope.

Determination of anabolic steroids by differential pulse polarography

Determination of anabolic steroids often requires the use of elaborate techniques such as gas chromatography - mass spectrometry (GC-MS), gas liquid chromatography (GLC) and more recently high performance liquid chromatography (HPLC). Most of these methods employ derivatisation techniques prior to detection which makes them tedious and relatively time consuming. Other methods demand a great deal of skill. A simple and rapid analytical method, based on differential pulse polarography at a dropping mercury electrode has been developed for the determination of various anabolic steroids in a range of commercially available pharmaceutical preparations. Detailed investigation of the electrochemical behaviour of these steroids was made in order to elucidate the electrode processes involved, in addition to optimising the method. Several other analytical methods such as GC-MS, NMR, ultraviolet (UV), infrared (IR) spectroscopy were also used to confirm the products of the chemical and electrochemical reactions. Possible reactions are suggested. Various extraction procedures were examined for separation of selected steroids from the oil-based or pill matrix and their suitability for polarographic determination is discussed.