Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

Phytoplankton Cell Size Reduction in Response to Warming Mediated by Nutrient Limitation

Shrinking of body size has been proposed as one of the universal responses of organisms to global climate warming. Using phytoplankton as an experimental model system has supported the negative effect of warming on body-size, but it remains controversial whether the size reduction under increasing temperatures is a direct temperature effect or an indirect effect mediated over changes in size selective grazing or enhanced nutrient limitation which should favor smaller cell-sizes. Here we present an experiment with a factorial combination of temperature and nutrient stress which shows that most of the temperature effects on phytoplankton cell size are mediated via nutrient stress. This was found both for community mean cell size and for the cell sizes of most species analyzed. At the highest level of nutrient stress, community mean cell size decreased by 46% per degrees C, while it decreased only by 4.7% at the lowest level of nutrient stress. Individual species showed qualitatively the same trend, but shrinkage per degrees C was smaller. Overall, our results support the hypothesis that temperature effects on cell size are to a great extent mediated by nutrient limitation. This effect is expected to be exacerbated under field conditions, where higher temperatures of the surface waters reduce the vertical nutrient transport

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Beeldcultuur, een drieluik.I: Deconstructie van het fenomeen culturele studies

An important process in glass manufacture is the forming of the product. The forming process takes place at high rate, involves extreme temperatures and is characterised by large deformations. The process can be modelled as a coupled thermodynamical/mechanical problem including the interaction between glass, air and equipment. In this paper a general mathematical model for glass forming is derived, which is specified for different forming processes, in particular pressing and blowing. The model should be able to correctly represent the flow of the glass and the energy exchange during the process. Various modelling aspects are discussed for each process, while several key issues, such as the motion of the plunger and the evolution of the glass-air interfaces, are examined thoroughly. Finally, some examples of process simulations for existing simulation tools are provided

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Deformation-related volcanism in the Pacific Ocean linked to the Hawaiian-Emperor bend

Ocean islands, seamounts and volcanic ridges are thought to form above mantle plumes. Yet, this mechanism cannot explain many volcanic features on the Pacific Ocean floor and some might instead be caused by cracks in the oceanic crust linked to the reorganization of plate motions. A distinctive bend in the Hawaiian–Emperor volcanic chain has been linked to changes in the direction of motion of the Pacific Plate, movement of the Hawaiian plume, or a combination of both. However, these links are uncertain because there is no independent record that precisely dates tectonic events that affected the Pacific Plate. Here we analyse the geochemical characteristics of lava samples collected from the Musicians Ridges, lines of volcanic seamounts formed close to the Hawaiian–Emperor bend. We find that the geochemical signature of these lavas is unlike typical ocean island basalts and instead resembles mid-ocean ridge basalts. We infer that the seamounts are unrelated to mantle plume activity and instead formed in an extensional setting, due to deformation of the Pacific Plate. 40Ar/39Ar dating reveals that the Musicians Ridges formed during two time windows that bracket the time of formation of the Hawaiian–Emperor bend, 53–52 and 48–47 million years ago. We conclude that the Hawaiian–Emperor bend was formed by plate–mantle reorganization, potentially triggered by a series of subduction events at the Pacific Plate margins