Surveying activated sludge changes during acclimation with artificial wastewater

Many processes in the chemical and pharmaceutical industries generate wastewater containing organic toxic compounds and other kinds of xenobiotics. Usually, biological treatments are used to degrade a great quantity of these substances. However, most of the time, the microorganisms are not adapted and the treatment can be blocked. Therefore, the first step to make a continuous reactor operative is the acclimation, i.e., the adaptation of the microorganisms to a specific substrate. During this particular step of the process there is a selection and a multiplication of specialized microorganisms and physiological transformations can occur in their metabolic system. Furthermore, combining image processing techniques have already been successfully used to elucidate the activated sludge morphological changes for both aggregated and filamentous bacteria contents, during such processes. The experimental set-up is composed of an aerated reactor and a clarifier. The sludge is recycled from the clarifier by a peristaltic pump. The complete mixing inside the reactor is guaranteed by the diffusion of air from its bottom. The reactor was inoculated with biomass collected from a wastewater treatment plant and fed with an artificial wastewater based on meat extract. During acclimation, chemical parameters were measured in the influent, reactor and effluent, in order to verify the stability of the process. To complete the evaluation of the process, microscopy acquisition and image processing and analysis techniques were performed for aggregates and filamentous bacteria characterization for bright field, Gram and poly-β-hydroxybutyrate (PHB) staining images. The information extracted from those images allowed for aggregates and filamentous bacteria contents inspection, identification of PHB storing microorganisms and, gram-positive and gram-negative filamentous bacteria recognition. Figure 1 presents activated sludge samples at the beginning and at the end of the acclimation phase. It was found in this study that biomass changes during the acclimation phase could be effectively monitored, combining image analysis information and chemical parameters

Chronic Treatment with a Promnesiant GABA-A α5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model

Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained in the Morris water maze task. In euploid mice, chronic treatment with α5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with α5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after α5IA treatment was observed. IEG expression regulation after α5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of α5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition

Characterization of nanomedicines’ surface coverage using molecular probes and capillary electrophoresis

International audienceA faithful characterization of nanomedicine (NM) is needed for a better understanding of their in vivo outcomes. Size and surface charge are studied with well-established methods. However, other relevant parameters for the understanding of NM behavior in vivo remain largely inaccessible. For instance, the reactive surface of nanomedicines, which are often grafted with macromolecules to decrease their recognition by the immune system, is excluded from a systematic characterization. Yet, it is known that a subtle modification of NMs' surface characteristics (grafting density, molecular architecture and conformation of macromolecules) is at the root of major changes in the presence of biological components. In this work, a method that investigates the steric hindrance properties of the NMs’ surface coverage based on its capacity to exclude or allow adsorption of well-defined proteins was developed based on capillary electrophoresis. A series of proteins with different molecular weights (MW) were used as molecular probes to screen their adsorption behavior on nanoparticles bearing different molecular architectures at their surface. This novel strategy evaluating to some degree a functionality of NMs can bring additional information about their shell property and might allow for a better perception of their behavior in the presence of biological components. The developed method could discriminate nanoparticles with a high surface coverage excluding high MW proteins from nanoparticles with a low surface coverage that allowed high MW proteins to adsorb on their surface. The method has the potential for further standardization and automation for a routine use. It can be applied in quality control of NMs and to investigate interactions between proteins and NM in different situations

Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly

Boundary Limitation of Wavenumbers in Taylor-Vortex Flow

We report experimental results for a boundary-mediated wavenumber-adjustment mechanism and for a boundary-limited wavenumber-band of Taylor-vortex flow (TVF). The system consists of fluid contained between two concentric cylinders with the inner one rotating at an angular frequency $\Omega$. As observed previously, the Eckhaus instability (a bulk instability) is observed and limits the stable wavenumber band when the system is terminated axially by two rigid, non-rotating plates. The band width is then of order $\epsilon^{1/2}$ at small $\epsilon$ ($\epsilon \equiv \Omega/\Omega_c - 1$) and agrees well with calculations based on the equations of motion over a wide $\epsilon$-range. When the cylinder axis is vertical and the upper liquid surface is free (i.e. an air-liquid interface), vortices can be generated or expelled at the free surface because there the phase of the structure is only weakly pinned. The band of wavenumbers over which Taylor-vortex flow exists is then more narrow than the stable band limited by the Eckhaus instability. At small $\epsilon$ the boundary-mediated band-width is linear in $\epsilon$. These results are qualitatively consistent with theoretical predictions, but to our knowledge a quantitative calculation for TVF with a free surface does not exist.Comment: 8 pages incl. 9 eps figures bitmap version of Fig

Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice

An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that α5IA restores learning and memory functions of Ts65Dn mice in the novel-object recognition and in the Morris water maze tasks. Furthermore, we show that following behavioural stimulation, α5IA enhances learning-evoked immediate early gene products in specific brain regions involved in cognition. Importantly, acute and chronic treatments with α5IA do not induce any convulsant or anxiogenic effects that are associated with GABA-A antagonists or non-selective inverse agonists of the GABA-A-benzodiazepine receptors. Finally, chronic treatment with α5IA did not induce histological alterations in the brain, liver and kidney of mice. Our results suggest that non-convulsant α5-selective GABA-A inverse agonists could improve learning and memory deficits in DS individuals

Association of plasma Aβ40/Aβ42 ratio and brain Aβ accumulation: testing a whole-brain PLS-VIP in individuals at risk of Alzheimer's disease

Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares, in unraveling the association between plasma Aβ42/Aβ40 ratio and an extensive set of brain regions characterized through molecular imaging of Aβ accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma Aβ42/40 ratio was associated with Aβ-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted - including the central executive and salience networks - which likely have a selective vulnerability to incipient Aβ accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions