Medial Prefrontal-Hippocampal Connectivity and Motor Memory Consolidation in Depression and Schizophrenia

Item does not contain fulltextBACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We investigated patients with depression and schizophrenia, as well as healthy control subjects (each n = 16), under a motor memory consolidation protocol with functional magnetic resonance imaging and polysomnography. RESULTS: In a sequential finger-tapping task associated with the degree of hippocampal-prefrontal cortex functional connectivity during the task, significantly less overnight improvement was identified as a common deficit in both patient groups. A task-related overnight decrease in activation of the basal ganglia was observed in control subjects and schizophrenia patients; in contrast, patients with depression showed an increase. During the task, schizophrenia patients, in comparison with control subjects, additionally recruited adjacent cortical areas, which showed a decrease in functional magnetic resonance imaging activation overnight and were related to disease severity. Effective connectivity analyses revealed that the hippocampus was functionally connected to the motor task network, and the cerebellum decoupled from this network overnight. CONCLUSIONS: While both patient groups showed similar deficits in consolidation associated with hippocampal-prefrontal cortex connectivity, other activity patterns more specific for disease pathology differed.10 p

Synthesis optimization of carbon-supported ZrO2 nanoparticles from different organometallic precursors

We report here the synthesis of carbon-supported ZrO2 nanoparticles from zirconium oxyphthalocyanine (ZrOPc) and acetylacetonate [Zr(acac)4]. Using thermogravimetric analysis (TGA) coupled with mass spectrometry (MS), we could investigate the thermal decomposition behavior of the chosen precursors. According to those results, we chose the heat treatment temperatures (THT) using partial oxidizing (PO) and reducing (RED) atmosphere. By X-ray diffraction we detected structure and size of the nanoparticles; the size was further confirmed by transmission electron microscopy. ZrO2 formation happens at lower temperature with Zr(acac)4 than with ZrOPc, due to the lower thermal stability and a higher oxygen amount in Zr(acac)4. Using ZrOPc at THT C900 °C, PO conditions facilitate the crystallite growth and formation of distinct tetragonal ZrO2, while with Zr(acac)4 a distinct tetragonal ZrO2 phase is observed already at THT C750 °C in both RED and PO conditions. Tuning of ZrO2 nanocrystallite size from 5 to 9 nm by varying the precursor loading is also demonstrated. The chemical state of zirconium was analyzed by X-ray photoelectron spectroscopy, which confirms ZrO2 formation from different synthesis routes

Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.

International audienceThe pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome

The protein histidine phosphatase LHPP is a tumour suppressor

Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic

mTOR in aging, metabolism, and cancer

The target of rapamycin (TOR) is a highly conserved serine/threonine kinase that is part of two structurally and functionally distinct complexes, TORC1 and TORC2. In multicellular organisms, TOR regulates cell growth and metabolism in response to nutrients, growth factors and cellular energy. Deregulation of TOR signaling alters whole body metabolism and causes age-related disease. This review describes the most recent advances in TOR signaling with a particular focus on mammalian TOR (mTOR) in metabolic tissues vis-a-vis aging, obesity, type 2 diabetes, and cancer

mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior

Orexigenic agouti-related protein/neuropeptide Y (Agrp/NPY) neurons and an orexigenic pro-opiomelanocortin (POMC) neurons of the hypothalamus regulate feeding behavior and energy homeostasis. An understanding of the molecular signaling pathways that regulate Agrp/NPY and POMC function could lead to novel treatments for metabolic disorders. Target of Rapamycin Complex 1 (TORC1) is a nutrient-activated protein kinase and central controller of growth and metabolism. We therefore investigated the role of mammalian TORC1 (mTORC1) in Agrp neurons. We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor KO) mice. Agrp-raptor KO mice displayed reduced, non-circadian expression of Agrp and NPY but normal feeding behavior and energy homeostasis on both normal and high fat diet. Thus, mTORC1 in Agrp neurons controls circadian expression of orexigenic neuropeptides but is dispensable for the regulation of feeding behavior and energy metabolism

Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells.

International audienceWe report here that apelin (65-77) activates p70 S6 kinase (p70S6K), not only in CHO cells that have been stably transfected with the apelin receptor, but also in umbilical endothelial cells (HUVEC), which express it endogenously. Apelin (65-77) induces a time-dependent phosphorylation of p70S6K at residues T421/S424 and T389. This dual phosphorylation is associated with two transduction cascades, involving a PI3K pathway and an ERK pathway, respectively. The PI3K pathway, which can be blocked by wortmannin, leads to phosphorylation of Akt at residues T308 or S473, which then promotes the phosphorylation of p70S6K at T421/S424 and T389. The ERK pathway is blocked by PD 098059, a MEK inhibitor, and results in the phosphorylation of p70S6K at T421/S424. Phosphorylation both of Akt and p70S6K is abrogated by pretreatment with pertussis toxin (PTX) and an inhibitor of atypical PKCs. In addition, we demonstrate that apelin (65-77) also increases the enzymatic activity of p70S6K and that the effects of the previously mentioned inhibitors on the level of T389 phosphorylation correlate with their action on enzyme activity. Interestingly, the main findings were reproduced in umbilical endothelial cells and apelin (65-77) promoted thymidine incorporation into DNA of these cells, revealing that apelin is a new mitogenic peptide for the endothelial cell

mTOR signaling in liver disease

The target of rapamycin (TOR) is a highly conserved serine/threonine kinase that forms two structurally and functionally distinct complexes, TORC1 and TORC2. In response to nutrients, growth factors and cellular energy, mammalian TOR (mTOR) controls cell growth and metabolism. mTOR plays an important role in metabolic organs, particularly in the liver, to mediate whole-body energy homeostasis. Dysregulation of mTOR signaling is associated with the development of several metabolic diseases such as diabetes, obesity, and cancer. Here, we review the role of hepatic mTORC1 and mTORC2 in linking metabolism, cancer development, and circadian rhythm-related processes

Comparative analysis of milk and cheese produced in the Pélardon PDO production zone based on their phenolic profiles

 Goat milk and cheese samples were collected from two different areas in the Pelardon PDO production zone, in order to explore the diversity of their phenolic profiles and try to relate it to variations in feeding practices. The results showed a diversity in the phenolic profiles of both milk and cheese samples, which was attributed to the heterogeneity of the vegetation and soil as well as the diverse farming and grazing methods applied. Nevertheless, the statistical analysis failed to reveal a link between milk and cheese phenolic composition and the production area or the feeding system. Data will require a more detailed analysis using informations from the farmer inquiries, in order to try to elucidate the main factors of feeding practices acting on milk and cheese phenolic composition