The role of financial intermediaries in monetary policy transmission

The recent financial crisis has stimulated theoretical and empirical research on the propagation mechanisms underlying business cycles, in particular on the role of financial frictions. Many issues concerning the interactions between banking and monetary policy forced policy makers to redefine economic policies, and motivated macroeconomists to focus on the implications of financial intermediation constraints for asset price fluctuations, the behavior of non-financial firms, households, governments and in turn for real macroeconomic performance. This paper surveys research on the role of financial intermediaries and financial frictions in the transmission of monetary policy and discusses how to design both the new banking regulatory and supervisory structures and monetary policy in order to stabilize the economy. It also serves as an introduction to this special issue

Genomic and Non-genomic Action of Neurosteroids in the Peripheral Nervous System

Since the former evidence of biologic actions of neurosteroids in the central nervous system, also the peripheral nervous system (PNS) was reported as a structure affected by these substances. Indeed, neurosteroids are synthesized and active in the PNS, exerting many important actions on the different cell types of this system. PNS is a target for neurosteroids, in their native form or as metabolites. In particular, old and recent evidence indicates that the progesterone metabolite allopregnanolone possesses important functions in the PNS, thus contributing to its physiologic processes. In this review, we will survey the more recent findings on the genomic and non-genomic actions of neurosteroids in nerves, ganglia, and cells forming the PNS, focusing on the mechanisms regulating the peripheral neuron-glial crosstalk. Then, we will refer to the physiopathological significance of the neurosteroid signaling disturbances in the PNS, in to identify new molecular targets for promising pharmacotherapeutic approaches

Neurosteroids involvement in the epigenetic control of memory formation and storage

Memory is our ability to store and remember past experiences; it is the result of changes in neuronal circuits of specific brain areas as the hippocampus. During memory formation, neurons integrate their functions and increase the strength of their connections, so that synaptic plasticity is improved and consolidated. All these processes recruit several proteins at the synapses, whose expression is highly regulated by DNA methylation and histone tails posttranslational modifications. Steroids are known to influence memory process, and, among them, neurosteroids are implicated in neurodegenerative disease related to memory loss and cognitive impairment. The epigenetic control of neurosteroids involvement in memory formation and maintenance could represent the basis for neuroregenerative therapies

Regulation of Schwann cells oncotransformation by changes in Nf2/merlin expression, Hippo/YAP signaling and DNA methylation

Schwann cell (SC) express the Neurofibromin type 2 gene (Nf2), encoding the tumor suppressor protein merlin, a cytoskeleton-associated protein regulating cell proliferation and survival. Nf2/merlin inactivation causes protein loss and leads to SC transformation into a form of benign tumor called schwannoma. Moreover, Nf2/merlin is mutated in an autosomal dominant multiple syndrome, called neurofibromatosis type 2. In line with observation that physio/mechanical cues, such as environmental challenges, may be pathogenetically relevant for SC oncotransformation, we recently showed that the exposure to electromagnetic fields (EMFs) causes changes in SC Nf2/merlin expression, cell migration, chemotactic responsivity and cytoskeleton reorganization. We showed a downstream MAPK/Erk activation, involved in SC proliferation, as well as activation of Hippo/YAP signalling commonly altered during tumorigenesis. We also showed that some genes, known to be upstream or downstream mediators of Hippo (Amotl2, Dchs, Fat, Wnt1) were changed. Further studies on rat SC oncotransformation following acute EMF exposure (0.1 T, 50 Hz, 10 min) demonstrated that the number of cells in G1 phase was increased. Focus forming analysis, after repeated exposures, showed an increase in 3D SC growth. EMF affects also the SC epigenome, as total DNA methylation, de novo DNMT and HDAC were reduced. Furthermore, RT2-profile assay evidenced that genes crucial for SCs are upregulated in EMF exposed cells. Overall, we identified some mechanisms responsible of environmental-induced SC changes toward a proliferative/migrating state, which may be pathologically relevant for nerve tumor development

PBCs environmental pollution and epigenome: a new role for androgen receptor-dependent modulation?

Epigenome is an important target of environmental effects, modulating disease susceptibility during the whole life. In our previous studies we have demonstrated that prenatal exposure to polychlorinated biphenyls (PCBs), an important class of endocrine disruptors, alters in liver some histone post-translational modifications (H3K4me3/H4K16Ac) and the expression of the corresponding modulating enzymes (Jarid1b/SirtT1) and reduces the androgen receptor (AR) levels1. Furthermore, it is known that steroid receptors could act also as co-regulator of histone modification enzymes. It is also remarkable that AR and Jarid1b (demethylating enzyme) interact each other and that Jarid1b is able to potentiate the transcriptional activity of AR2. The AR down-regulation, shown by our data, is not directly related to the reduction of H3K4me3 levels in the AR promoter, as our ChIP experiments have indicated1. The observed AR reduction might be related to the down-regulation of AR induced by its own activation3. The aim of this work was to characterize the complex scenario of AR involvement in regulating histone modifications. First of all, we investigated if a reconstituted mixture of PCBs is able to modulate AR transcriptional activity; we observed that PCBs are able to induce AR mediated transcription in a dose dependent way and that Jarid1b presence potentiates the PCB effect on AR transcriptional activity. Furthermore we showed that the localization of PCB- activated AR is influenced by Jarid1b presence. Finally, using AR promoter fused with a reporter gene, we found that PCBs are able to auto-downregulate AR, especially at the presence of Jarid1b. In conclusion it is possible to hypothesize that AR modulation exerted by PCB pass through chromatin structure remodelling. It remains to clarify if AR is involved in mediating PCB induced disruption of Jarid1b

Transient expression of the 5alpha-reductase type 2 isozyme in the rat brain in late fetal and early postnatal life

The enzyme 5alpha-reductase plays a key role on several brain functions controlling the formation of anxiolytic/anesthetic steroids derived from progesterone and deoxycorticosterone, the conversion of testosterone to dihydrotestosterone, and the removal of excess of potentially neurotoxic steroids. Two 5alpha-reductase isoforms have been cloned: 5alpha-reductase type 1 is widely distributed in the body, and 5alpha-reductase type 2 is confined to androgen-dependent structures. In this study, the gene expression of the two 5alpha-reductase isozymes has been analyzed in fetal, postnatal, and adult rat brains by RT-PCR followed by Southern analysis. 5Alpha-reductase type 1 messenger RNA is always detectable in the rat brain [from gestational day 14 (GD14) to adulthood]. 5Alpha-reductase type 2 messenger RNA expression is undetectable on GD14, increases after GD18, peaks on postnatal day 2, then decreases gradually, becoming low in adulthood. This pattern of expression appears to be correlated with the rate of production of testosterone by the testis. The possible control by androgens of gene expression of the two isozymes has been studied in brain tissues of animals exposed in utero to the androgen antagonist flutamide; the sex of the animals was determined by genetic sex screening of the SRY gene located on the Y-chromosome. In the brain of male embryos, flutamide treatment inhibited the expression of 5alpha-reductase type 2; this effect was much less pronounced in females. Moreover, 5alpha-reductase type 2 gene expression in cultured hypothalamic neurons is highly induced by testosterone and by the phorbol ester 12-O-tetradecanoyl-phorbol-13 acetate. The transient, androgen-regulated, expression of 5alpha-reductase type 2 overlaps the critical period of development, which may be important for sexual differentiation of the brain and for the formation of anxiolytic/anesthetic steroids involved in the stress responses associated with parturition

PCSK9 induces a pro-inflammatory response in macrophages.

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009<\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR

Timing of hospital admission in labour: latent versus active phase, mode of birth and intrapartum interventions: a correlational study

Background Hospitalization of women in latent labour often leads to a cascade of unnecessary intrapartum interventions, to avoid potential disadvantages the recommendation should be to stay at home to improve women’s experience and perinatal outcomes. Aim The primary aim of this study was to investigate the association between hospital admission diagnosis (latent vs active phase) and mode of birth. The secondary aim was to explore the relationship between hospital admission diagnosis, intrapartum intervention rates and maternal/neonatal outcomes. Methods A correlational study was conducted in a large Italian maternity hospital. Data from January 2013 to December 2014 were collected from the hospital electronic records. 1.446 records of low risk women were selected. These were dichotomized into two groups based on admission diagnosis: ‘latent phase’ or ‘active phase’ of labour. Findings 52.7% of women were admitted in active labour and 47.3% in the latent phase. Women in the latent phase group were more likely to experience a caesarean section or an instrumental birth, artificial rupture of membranes, oxytocin augmentation and epidural analgesia. Admission in the latent phase was associated with higher intrapartum interventions, which were statistically correlated to the mode of birth. Conclusions Women admitted in the latent phase were more likely to experience intrapartum interventions, which increase the probability of caesarean section. Maternity services should be organized around women and families needs, providing early labour support, to enable women to feel reassured facilitating their admission in labour to avoid the cascade of intrapartum interventions which increases the risk of caesarean section