Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Modified Galacto- or Fuco-Clusters Exploiting the Siderophore Pathway to Inhibit the LecA- or LecB-Associated Virulence of Pseudomonas aeruginosa

Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localised in the outer membrane and inside the bacterium. The resulting glycocluster–pseudosiderophore conjugates were evaluated as Trojan horses to cross the outer membrane of PA by iron transport. The data suggest that glycoclusters with catechol moieties are able to hijack the iron transport, whereas those with hydroxamates showed strong nonspecific interactions. Mono- and tricatechol galactoclusters ( G1C and G3C ) were evaluated as inhibitors of infection by PA in comparison with the free galactocluster ( G0 ). All of them exhibited an inhibitory effect between 46 to 75 % at 100 μM, with a higher potency than G0 . This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism.     

Cover Feature: A Comparative Study of in vitro Assays for Predicting the Nonspecific Binding of PET Imaging Agents in vivo (ChemMedChem 7/2020)

Nonspecific binding (NSB) is a key parameter in optimizing PET imaging tracers. We compared the ability to predict NSB of three available methods: LIMBA, rat f_u,brain, and CHI(IAM). Even though NSB is often associated with lipophilicity, we observed that logD does not correlate with any of these assays, clearly indicating that lipophilicity, while influencing NSB, is insufficient to predict it. A cross-comparison of the methods showed that all three correlate and are useful predictors of NSB. The three assays, however, rank the molecules slightly differently, illustrating the challenge of comparing molecules within a narrow chemical space. We also noted that CHI(IAM) values more effectively predict V_NS, a measure of in vivo NSB in the human brain. CHI(IAM) measurements might be a closer model of the actual physicochemical interaction between PET tracer candidates and cell membranes, and seems to be the method of choice for the optimization of in vivo NSB.     

Temperature stability of a pure metakaolin based K-geopolymer: Part 2. Variations in the mesoporous network and its rehydration stability

The thermal behavior of a model MK-based K-geopolymer was investigated between room temperature and 1400°C in order to evaluate its potentiality for high-temperature applications. The purpose of our study was to monitor the behavior of a geopolymer during a temperature rise in order to better understand its variations with respect to temperature. The works from the present paper focus only changes in the porous network; it follows a first part devoted to variations in the mineral matrix. The results obtained here show that the geopolymer material preserves its porous integrity up to 800°C, while maintaining the reversibility of water exchanges corresponding to about 25 weight percent. Together with the results of part 1, the findings of this study allow us to affirm that geopolymer materials are only very little affected by temperatures up to 800°C, or even 900°C (keeping its mesoporous amorphous structure).     

Biomonitoring of the adverse effects induced by the chronic exposure to lead and cadmium on kidney function: usefulness of alpha-glutathione S-transferase

A successful prevention of renal diseases induced by occupational exposure to lead (Pb) and/or cadmium (Cd) largely relies on the capability to detect nephrotoxic effects at a stage when they are still reversible or at least not yet compromising renal function. Hence, the aim of this cross-sectional study was to evaluate the usefulness of a set of early biological markers of oxidative stress or nephrotoxicity for the biomonitoring of workers occupationally exposed to Pb and/or Cd in a non-ferrous metal smelter, and gender, age, socioeconomic status, smoking habits, and drug use-matched control individuals. In exposed subjects, mean levels of Pb in blood and urine were also 387.1+/-99.1 microg Pb/L (1.868+/-0.478 micromol Pb/L) and 217.7+/-117.7 microg Pb/g creatinine (1.051+/-0.568 micromol Pb/g creatinine), and mean levels of Cd in blood and urine were 3.26+/-2.11 microg Cd/L (0.029+/-0.019 micromol Cd/L) and 2.51+/-1.89 microg Cd/g creatinine (0.022+/-0.017 micromol Cd/g creatinine), suggesting thereby relatively low occupational exposure levels. Statistically significant variations in zinc protoporphyrin, malondialdehyde, retinol binding protein, alpha-glutathione S-transferase, and urinary protein levels were reported between the two groups, and were closely correlated with Pb and/or Cd exposure levels. Variations in alphaGST levels were closely associated with Pb exposure. Taken together, these results suggest the use of alpha-glutathione S-transferase excretion in urine as a hallmark of early changes in the proximal tubular integrity.     

Mitigation of Temperature Gradients in the Buffer Tank of a Natural Circulation Loop Simulating Passive Decay Heat Removal in a Pool Type Reactor

Abstract

This study considers the decay heat removal through passive systems (i.e., natural convection) in the pool-type experimental reactor MYRRHA (SCK?CEN). The low velocities associated with natural convection may cause a degradation of the thermal mixing in the upper plenum of the reactor: buoyancy dominated phenomena, such as stratification, buoyant jets or convective cells may occur. The large temperature gradients associated with these phenomena may induce thermal loads on the structure, compromising its integrity. The objectives of this work are, in order, (1) achieving an understanding of the fluid mechanics leading to the formation of thermal gradients in the upper plenum and (2) mitigating the temperature gradients the upper plenum’s geometry. The methodology chosen to address the problem is experimental. A ''two-dimensional'' water facility modeling a slab of the reactor's primary loop was designed. Simultaneous measurements of velocity and temperature were performed in the model's buffer tank using thermocouples and innovative optical imaging techniques. It was observed that vertical thermal gradients develop in the tank because of the combined effect of stratification and advection. Important reductions of local gradients were observed when changing porosity and position of upper plenum’s buffer plates.     

Evaluation of the quality of collaboration between the client and the therapist in phobia treatments

A growing number of empirical studies evaluate the influence of Mental Health (MH) technology on the clinical effectiveness, the therapeutic relationship (i.e., therapeutic alliance), and usability issues. However, to the authors’ knowledge, no studies have yet been performed regarding the influence of technology on the therapeutic process in terms of collaboration. This study evaluates the quality of collaboration between the client and therapist in Augmented Reality Exposure Therapy (ARET) context and the traditional, In Vivo Exposure Therapy (IVET) context with the Therapeutic Collaborative Scale (TCS). Twenty participants received an intensive session of cognitive behavioral therapy in either a technology-mediated therapeutic context or in a traditional therapeutic context. The results indicate that both therapeutic conditions show high collaboration scores. However, the asymmetry of roles between the therapist and the client under both conditions were detected. Also, a greater level of distraction was observed for therapists in ARET, which affected the quality of the therapists’ involvement in the therapeutic session. The implications of these results are discussed.     

Power MOSFET quality and robustness enhancement with a new QBD characterization performed at probe–die–wafer level

The quality of the gate oxide is a central parameter for power MOSFET devices dedicated to automotive applications. Reliability is systematically evaluated through electrical tests. The purpose of this study is to apply the Q_BD test directly at probe–die–wafer level and to correlate its results with reliability test conclusions. In other words, this new kind of Q_BD test is a monitor of power MOSFET robustness which helps identify extrinsic failures and the process steps responsible. In summary, it is an accurate and fast measurement method of identifying weakened parts and enhancing device quality.     

Analysis of muscle length effect on an S type motor-unit fractional multi-model

Muscle models are useful in bio-inspired robotic, because they allow to reproduce accurately natural motion. When they are used for robotic issue, they need to be compact and embeddable. The non-integer model order has the advantage to ensure a parametrical parsimony that permits to implant it easily on an embedded system. Thus, a fractional multi-model of muscle was identified and presented in later paper. This model is able to predict the response of a motor unit to an electrical stimulation, considering isometric contractions (that is to say, muscle length is constant). There are three different physiological types of motor unit (FR, FF, and S). The aim of this work is to study muscle length impact on the multi-model and the limitations of the linear multi-model. Previous paper was published using FR type motor unit. In this paper, the results of the study using S type motor unit are presented.