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.     

Quantitative UPLC‐MS/MS analysis of chlorogenic acid derivatives in antioxidant fractionates from dandelion (Taraxacum officinale) root

While qualitative studies have identified chlorogenic acids in antioxidant extracts, particularly ethyl acetate‐derived extracts, of Taraxacum officinale, quantitative analysis of these phenolic compounds remains largely unreported for this species. In this study, bioactivity‐guided fractionation of an antioxidant crude ethyl acetate extract (DPPH = 295.481 ± 0.955 mg TE g^?1 extract) from T. officinale root resulted in a number of reverse‐phase fractions that demonstrated high antioxidant activity (DPPH = 1058.733–1312.136 mg TE g^?1 extract), stronger than that of the synthetic antioxidant Trolox^®. UPLC‐MS/MS screening of these fractions for the presence of selected mono‐ and di‐caffeoylquinic acids revealed large quantities of 1,5‐dicaffeoylquinic acid present in several fractions (853.052–907.324 μg mg^?1), respectively. Due to the antioxidant potency and high levels of 1,5‐dicaffeoylquinic acid observed in these fractions, it was concluded that specifically this chlorogenic acid derivative is a major contributor to the antioxidant efficacy of dandelion root.     

Magnetic Nanoparticle Arrays Self-Assembled on Perpendicular Magnetic Recording Media

We study magnetic-field directed self-assembly of magnetic nanoparticles onto templates recorded on perpendicular magnetic recording media, and quantify feature width and height as a function of assembly time. Feature widths are determined from Scanning Electron Microscope (SEM) images, while heights are obtained with Atomic Force Microscopy (AFM). For short assembly times, widths were ~150 nm, while heights were ~14 nm, a single nanoparticle on average with a 10:1 aspect ratio. For long assembly times, widths approach 550 nm, while the average height grows to 3 nanoparticles, ~35 nm; a 16:1 aspect ratio. We perform magnetometry on these self-assembled structures and observe the slope of the magnetic moment vs. field curve increases with time. This increase suggests magnetic nanoparticle interactions evolve from nanoparticle–nanoparticle interactions to cluster–cluster interactions as opposed to feature–feature interactions. We suggest the aspect ratio increase occurs because the magnetic field gradients are strongest near the transitions between recorded regions in perpendicular media. If these gradients can be optimized for assembly, strong potential exists for using perpendicular recording templates to assemble complex heterogeneous materials.     

A self‐scalable load injection service

Load testing of applications is an important and costly activity for software provider companies. Classical solutions are very difficult to set up statically, and their cost is prohibitive in terms of both human and hardware resources. Virtualized cloud computing platforms provide new opportunities for stressing an application's scalability, by providing a large range of flexible and less expensive (pay‐per‐use model) computation units. On the basis of these advantages, load testing solutions could be provided on demand in the cloud. This paper describes a Benchmark‐as‐a‐Service solution that automatically scales the load injection platform and facilitates its setup according to load profiles. Our approach is based on: (i) virtualization of the benchmarking platform to create self‐scaling injectors; (ii) online calibration to characterize the injector's capacity and impact on the benched application; and (iii) a provisioning solution to appropriately scale the load injection platform ahead of time. We also report experiments on a benchmark illustrating the benefits of this system in terms of cost and resource reductions. Copyright © 2013 John Wiley & Sons, Ltd.     

Structure−Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents

Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.