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1.
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 GABAA 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.  相似文献   
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Clean Technologies and Environmental Policy - Biochar has caught great attention over the last decade, yielding a large number of publications in a broad range of disciplines. This scientometric...  相似文献   
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Using a qualitative case study of the transformations of the infrastructure of the Danish film field by the Danish Film Institute and its CEO, three basic questions about entrepreneurial agency are raised. The first deals with the relationship between the institutional environment and the personal backgrounds of entrepreneurial actors. The study finds that certain actors can be seen as possessing extreme or unique levels of legitimacy resulting in being rewarded with tremendous resources and opportunities for strategic action. The second question has to do with how, and what sort of role transformations can take place from a structurally central, but static position in a field. Here ‘intermediary entrepreneurialism’ was used to penetrate and integrate the field in such a way as to turn a structurally fixed position from a weak to a strong nexus. The third question deals with how transformations can be effected by an organization that straddles three prominent institutional fields and logics – the state, market and artistic expression. Here, the key role of the term ‘professionalization’ is emphasized, arguing that this term proved evocative and compelling in each institutional field. The case also adds to our understanding of institutional and transformation processes in creative industries by focusing on two less‐studied contexts – the role and strategies of centrally placed actors in initiating and leading transformational activities, and the role that entrepreneurial ‘bureaucrats’ can play in transforming creative industries.  相似文献   
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Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.  相似文献   
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The Na2O-Cs2O-SiO2 system has been investigated by means of a new differential thermal analysis apparatus. Two compounds have been observed for the first time in the metasilicate and disilicate joins. The CsNaSi2O5 disilicate melts congruently at 1217 K and the peritectic fusion of the CsNaSiO3 metasilicate occurs at 1120 K.  相似文献   
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Increasing evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) differ in gastrotoxicity. This study aimed to compare the effects of a short-acting NSAID, tiaprofenic acid, with indomethacin on experimental gastric ulcer healing in a rat model. Similar anti-inflammatory and prostaglandin-inhibitory doses of indomethacin (1 mg/kg) and tiaprofenic acid (2 mg/kg) were administered to rats with acetic acid-induced ulcers. After 2 weeks treatment, rats were killed and ulcer size determined. In addition, histological sections of ulcers were assessed for ulcer contraction and mucosal regeneration. The degree of inhibition of prostaglandin E2 (PGE2) synthesis was 72% at 2 h after tiaprofenic acid and 64% at 2 h after indomethacin administration, respectively. Rats treated with indomethacin for 2 weeks had significantly larger ulcers, both macroscopically and microscopically, than controls. Rats treated with tiaprofenic acid for 2 weeks had ulcers of a similar size to those of controls. Indomethacin-treated ulcers showed a failure in mucosal regeneration. Tiaprofenic acid-treated ulcers had significantly more regeneration than indomethacin-treated ulcers. We conclude that tiaprofenic acid inhibits mucosal prostaglandin levels but does not inhibit experimental gastric ulcer healing. These findings suggest that inhibition of PGE2 synthesis is not the only factor in generating gastrotoxicity and that a shift to low gastrotoxic NSAID may be clinically worthwhile.  相似文献   
10.
The preoperative assessment of sciatica secondary to a herniated intervertebral disk has been radically changed over recent years due to the development of percutaneous treatment techniques which now offer an alternative to surgery. After recalling the terminology used for the position of a herniated lumbar disk in relation to the posterior common vertebral ligament (subligamentous or transligamentous hernia) and to describe whether or not the hernia is detached from the original disk (excluded or non-excluded hernia), the authors review the current state of the art of imaging for each type of herniated lumbar intervertebral disk.  相似文献   
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