The relation between hemispheric lateralisation and measures of immune competence and adherence in Human Immunodeficiency Virus Type 1 (HIV-1)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright © 2012 Sumner et al

Upscaling of bottom-generated turbulence in large-scale 3D models for sediment transport in estuaries and coastal zones

Currently used 3D numerical sediment transport models still fail to make good quantitative predictions. To a great extent, this can be attributed to the inadequate description of physical processes which occur at the subgrid scale level. From flume experiments it is known that particle-turbulence interactions near the bed significantly change the effective roughness experienced by the overlying water column. This results in different transport rates if not accounted for.From a theoretical perspective, bed load transport, sheet flow and fluid mud flow are all occurrences of supersaturated suspension flow in the inner near-bed layer comprising the viscous sublayer and the transient layer. Its thickness increases with sediment load, since particle-particle interactions (four-way coupling effects) consume considerable amounts of the available stream power. In order to know how much energy is left over to compute the transport capacity of the outer, fully-developed layer, it is necessary to quantify the energy budget in the inner layer.This is a difficult task. Every modelling approach has its draw-backs and limitations. Lagrangean particle tracking is hopeless, since the required number of particles to approach field conditions is much too high, and the volumes occupied by the particles cannot be neglected. Grain sizes are non-uniform in nature and concentrations near the bed very high, making it very difficult to give an accurate description of the momentum exchange between fluid and solid phase, which accounts for particle collisions. Therefore, in view of large-scale applications, a one-fluid approach is adopted. This implies that the momentum equation is solved for the suspension, together with a turbulence closure model and the sediment mass balance.Since the thickness of the supersaturated inner layer mostly is very small relative to the water depth and the vertical discretization in large scale applications, it is not possible to resolve this layer with a traditional low-Reynolds model approach, which requires a very fine grid. A new approach is proposed, where a modified Prandtl-mixing length (PML) model is used for the bed layer, and a new low-Reynolds model is applied in the outer layers. In this way it is possible to obtain a correct behaviour for tidal oscillating flow in estuaries, where low-Re effects enter high in the water column during slack water.The correction factor for the PML eddy viscosity and the damping functions for the low-Re k-epsilon turbulence model are constructed based on theoretical constraints, DNS and LES generated data, as well as experimental flume data. In parallel, LES and improved two-layer low-Re models are developed to simulate flow over rough bottoms without and with sediment, in order to generate data very close to the bed surface, where no measurements can be made. These additional data are used to help interpret experimental flume data, which always show relatively high experimental errors, and to extend the new damping functions for the cases with bottom roughness and suspended sediment.Preliminary results of the new coarse grid RANS model for open-channel flow with various roughness conditions without and with suspended sediment will be shown, compared to LES results for flow over a wavy bottom, low-Reynolds RANS results over rough bottom and experimental flume data

Expression and Localization of Mitochondrial Ferritin mRNA in Alzheimer's Disease Cerebral Cortex

Mitochondrial ferritin (MtF) has been identified as a novel ferritin encoded by an intron-lacking gene with specific mitochondrial localization located on chromosome 5q23.1. MtF has been associated with neurodegenerative disorders such as Friedreich ataxia and restless leg syndrome. However, little information is available about MtF in Alzheimer's disease (AD). In this study, therefore, we investigated the expression and localization of MtF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) as well as in situ hybridization histochemistry. We also examined protein expression using western-blot assay. In addition, we used in vitro methods to further explore the effect of oxidative stress and β-amyloid peptide (Aβ) on MtF expression. To do this we examined MtF mRNA and protein expression changes in the human neuroblastoma cell line, IMR-32, after treatment with Aβ, H2O2, or both. The neuroprotective effect of MtF on oxidative stress induced by H2O2 was measured by MTT assay. The in situ hybridization studies revealed that MtF mRNA was detected mainly in neurons to a lesser degree in glial cells in the cerebral cortex. The staining intensity and the number of positive cells were increased in the cerebral cortex of AD patients. Real-time PCR and western-blot confirmed that MtF expression levels in the cerebral cortex were significantly higher in AD cases than that in control cases at both the mRNA and the protein level. Cell culture experiments demonstrated that the expression of both MtF mRNA and protein were increased by treatment with H2O2 or a combination of Aβ and H2O2, but not with Aβ alone. Finally, MtF expression showed a significant neuroprotective effect against H2O2-induced oxidative stress (p<0.05). The present study suggests that MtF is involved in the pathology of AD and may play a neuroprotective role against oxidative stress

Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function

A Very High-Order Accurate Staggered Finite Volume Scheme for the Stationary Incompressible Navier–Stokes and Euler Equations on Unstructured Meshes

International audienceWe propose a sixth-order staggered finite volume scheme based on polynomial reconstructions to achieve high accurate numerical solutions for the incompressible Navier-Stokes and Euler equations. The scheme is equipped with a fixed-point algorithm with solution relaxation to speed-up the convergence and reduce the computation time. Numerical tests are provided to assess the effectiveness of the method to achieve up to sixth-order con-2 Ricardo Costa et al. vergence rates. Simulations for the benchmark lid-driven cavity problem are also provided to highlight the benefit of the proposed high-order scheme

Alterations of brain and cerebellar proteomes linked to Aβ and tau pathology in a female triple-transgenic murine model of Alzheimer's disease

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1M146V, APPswe, and tauP301L transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aβ- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aβ and tau, and ultimately offer novel targets for therapeutic intervention

RegaDB: Community-driven data management and analysis for infectious diseases

Summary: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB pr

Reelin Secreted by GABAergic Neurons Regulates Glutamate Receptor Homeostasis

BACKGROUND: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR). We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversibly changes the subunit composition of N-methyl-D-aspartate glutamate receptors (NMDARs) to a predominance of NR2B-containing NMDARs. Addition of recombinant or endogenously secreted reelin rescues the effects of protein secretion blockade and reverts the fraction of NR2B-containing NMDARs to control levels. Therefore, the continuous secretion of reelin is necessary to control the subunit composition of NMDARs in hippocampal neurons. CONCLUSIONS/SIGNIFICANCE: Our data show that the heterogeneity of reelin immunoreactivity correlates with distinct functional populations: neurons synthesizing and secreting reelin and/or neurons binding reelin. Furthermore, we show that continuous reelin secretion is a strict requirement to maintain the composition of NMDARs. We propose that reelin is a trans-neuronal messenger secreted by GABAergic neurons that regulates NMDARs homeostasis in postnatal hippocampus. Defects in reelin secretion could play a major role in the development of neuropsychiatric disorders, particularly those associated with deregulation of NMDARs such as schizophrenia