152 research outputs found

    Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: Focus on heteroreceptor complexes and related functional neurotrophic effects

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    Neuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe heteroreceptor complexes between GPCR and RTKs in the central nervous system (CNS) and their functional effects in controlling a variety of neuronal effects, ranging from development, proliferation, differentiation and migration, to survival, repair, synaptic transmission and plasticity. In this interaction, RTKs can also recruit components of the G protein signaling cascade, creating a bidirectional intricate interplay that provides complex control over multiple cellular events. These heteroreceptor complexes, by the integration of different signals, have recently attracted a growing interest as novel molecular target for depressive disorders

    Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

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    The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1). Following single injection of Oxotremorine-M (0.4 mg/kg) all Hsps examined were significantly increased in at least one of the time points studied (24, 48, and 72 hr). Treatment with Oxotremorine-M significantly increased the level of phosphorylated HSF1 in all time points studied, without change of protein levels. Similar pattern of Hsps changes was obtained following chronic Oxotremorine-M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic treatment for 10 days no changes were observed in Hsps. The muscarinic acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely block Oxotremorine-M effects on Hsps. In conclusion, considering the function of Hsps in protecting neuronal cells from deleterious proteotoxic stress, for example, protein mis-folding and aggregation, the results obtained indicate that muscarinic acetylcholine receptor activation may have implications in potential treatment of neurodegenerative disorders linked to protein aggregation, such as Alzheimer disease

    Recensione di Hongjian Wang. Decadence in Modern Chinese Literature and Culture. A Comparative and Literary-Historical Reevaluation. Cambria Press, 2020. 252p.

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    The volume is about the concept of "decadence" in literature. A "decadent" attitude can be found also in works of narrative of contemporary Chinese writer as the Author explains in the reviewed volume

    Yiyun Li’s A Thousand Years of Good Prayers and Murakami Haruki’s Men Without Women: Rarefaction and Suspension of Time 时间的稀薄及悬浮:李翊云的 A Thousand Years of Good Prayers(《千年修得共枕眠》) 和村上春树的女のいない男たち(《没有女人的男人们》)

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    This paper illustrates resonances of style in the two works, "A Thousand Years of Good Prayers" by the Chinese woman writer Yiyun Li and "Men Without Women" by the Japanese author Murakami Haruki, that present some similarities

    Danno non patrimoniale e responsabilità civile dei magistrati

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    Starting from the Constitutional Court’s ruling 205/2022, the author analyzes the civil liability of judges in respects of facts occurring in the performance of their duties. The decision establishes the constitutional illegitimacy of the art. 2 comma 1 of the law 117/1988 because, in its original formulation, the article limited the compensation of non-pecuniary damages to the ones resulting from the privation of personal freedom. Once outlined the fundamental junctures of the motivational process of the Constitutional Court’s ruling and after a brief examination of the reference discipline and case law on gross negligence of judges, the paper critically dwells on non-pecuniary damage and its compensability under article 2059 of the Civil Code

    Nicotine-induced fibroblast growth factor-2 restores the age-related decline of precursor cell proliferation in the subventricular zone of rat brain

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    Precursor cell proliferation is present in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus of adult rat and persists during aging although at reduced levels. Previous studies have shown that acute intermittent nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) expression in several brain regions of aged rats. The aim of the present investigation was to test the hypothesis that nicotine-induced expression of FGF-2 may restore the age-related decline of precursor cell proliferation. It was first demonstrated that nicotine treatment increases both mRNA and protein FGF-2 in the SVZ of aged male rats (18 months old). The effect of nicotine on precursor cell proliferation in the SVZ was studied by i.p. injection of 5-bromo-2'-deoxyuridine (BrdU) 40 mg/kg to label dividing cells. The nicotine treatment was found to significantly enhance precursor cell proliferation in the SVZ. This increase was sufficiently large to restore the age-related decline of proliferating precursor cells observed in aged rats to that found in young adult rats (3 months old). FGF-2 was expressed in GFAP-positive cells and may act via its receptor FGFR1 that was found expressed in nestin-positive cells of the SVZ. The data obtained demonstrated that the age-related decline of precursor cell proliferation may be counteracted by activating a trophic mechanism mediated by FGF-2

    An upstream enhancer and MEF2 transcription factors fine-tune the regulation of the Bdnf gene in cortical and hippocampal neurons

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    : The myocyte enhancer factor (MEF2) family of transcription factors, originally discovered for its pivotal role in muscle development and function, has emerged as an essential regulator in various aspects of brain development and neuronal plasticity. The MEF2 transcription factors are known to regulate numerous important genes in the nervous system, including brain-derived neurotrophic factor (BDNF), a small secreted neurotrophin responsible for promoting the survival, growth, and differentiation of neurons. The expression of the Bdnf gene is spatiotemporally controlled by various transcription factors binding to both its proximal and distal regulatory regions. While previous studies have investigated the connection between MEF2 transcription factors and Bdnf, the endogenous function of MEF2 factors in the transcriptional regulation of Bdnf remains largely unknown. Here, we aimed to deepen the knowledge of MEF2 transcription factors and their role in the regulation of Bdnf comparatively in rat cortical and hippocampal neurons. As a result, we demonstrate that the MEF2 transcription factor-dependent enhancer located at -4.8 kb from the Bdnf gene regulates the endogenous expression of Bdnf in hippocampal neurons. In addition, we confirm neuronal-activity dependent activation of the -4.8 kb enhancer in vivo. Finally, we show that specific MEF2 family transcription factors have unique roles in regulation of Bdnf, with the specific function varying based on the particular brain region and stimuli. Altogether, we present MEF2 family transcription factors as crucial regulators of Bdnf expression, finetuning Bdnf expression through both distal and proximal regulatory regions

    Tra il pensare e il fare in architettura: le arti del disegno e le metodologie BIM nella gestione del cantiere

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    There is, in Architecture, an intellectual responsibility that involves each author-designer about the relationship between time of conception and practical realization; the cycle of construction activities is a crucial stage in this production process. The most advanced procedures of Building Information Modeling (BIM) are an added value not only for the design but also for operations and controls on site during construction. To assess dynamics, opportunities and achievements of representation language supported by BIM technologies we will expose some experiments carried out by the research group who have achieved significant savings in production and adopted important amendments to construction process

    Rappresentare le dinamiche volumetriche

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    This paper covers an area of research that aims to represent on digital maps from Gis system the transformation of construction, the environment, the social evolution in the city of Milan from 2007. These studies where carried out during the project e Mapping from ANCE Milano where the author was coordinator. The purpose of the research was to share data bases collected from the city planning offices of the Municipality of Milano, their processing to give an overall representation of the volumetric dynamism of the city

    PROTEOMIC CHANGES INDUCED BY LOW-INTENSITY ENDURANCE EXERCISE IN MDX MOUSE QUADRICEPS: CORRELATION WITH REDUCTION OF MUSCLE DEGENERATION.

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    Previous study showed that low-intensity endurance exercise induced a significant recovery of damaged skeletal muscle in mdx mice, probably by reducing the degeneration of dystrophic muscle1. In order to explore the molecular basis of this observation, we perfomed a proteomic analysis to evaluate changes in proteins profiling of quadriceps dystrophic muscles of exercised versus sedentary mdx mice. Four protein spots were found significantly changed and were identified as three isoforms of Carbonic anhydrase 3 (CA3) and as superoxide dismutase [Cu-Zn] (SODC). Protein levels of CA3 isoforms were found significantly up-regulated in quadriceps of sedentary mdx mice (MDX-Sed) and were completely restored to wild type values in quadriceps of exercised mdx mice (MDX-Ex). Protein levels of SODC were found down-regulated in quadriceps of sedentary mdx mice and were significantly restored to wild type values in quadriceps of exercised mdx mice. These proteomic data, validated by Western blot analysis, indicate that low-intensity endurance exercise, by modulating some proteins involved in oxidative stress defense, may in part contribute to reduce the reported cell degeneration in mdx muscles1. Further investigations are needed to better define the extension of proteins change in MDX-Ex versus MDX-Sed mice and its correlation with the recovery of damaged fibers in MDX-Ex mice
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