Brain Derived Neurotrophic Factor (BDNF) Expression Is Regulated by MicroRNAs miR-26a and miR-26b Allele-Specific Binding

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an essential role in neuronal development and plasticity. MicroRNA (miRNAs) are small non-coding RNAs of about 22-nucleotides in length regulating gene expression at post-transcriptional level. In this study we explore the role of miRNAs as post-transcriptional inhibitors of BDNF and the effect of 3′UTR sequence variations on miRNAs binding capacity. Using an in silico approach we identified a group of miRNAs putatively regulating BDNF expression and binding to BDNF 3′UTR polymorphic sequences. Luciferase assays demonstrated that these miRNAs (miR-26a1/2 and miR-26b) downregulates BDNF expression and that the presence of the variant alleles of two single nucleotide polymorphisms (rs11030100 and rs11030099) mapping in BDNF 3′UTR specifically abrogates miRNAs targeting. Furthermore we found a high linkage disequilibrium rate between rs11030100, rs11030099 and the non-synonymous coding variant rs6265 (Val66Met), which modulates BDNF mRNA localization and protein intracellular trafficking. Such observation led to hypothesize that miR-26s mediated regulation could extend to rs6265 leading to an allelic imbalance with potentially functional effects, such as peptide's localization and activity-dependent secretion. Since rs6265 has been previously implicated in various neuropsychiatric disorders, we evaluated the distribution of rs11030100, rs11030099 and rs6265 both in a control and schizophrenic group, but no significant difference in allele frequencies emerged. In conclusion, in the present study we identified two novel miRNAs regulating BDNF expression and the first BDNF 3′UTR functional variants altering miRNAs-BDNF binding

Early warning of systemic risk in global banking: eigen-pair R number for financial contagion and market price-based methods

We analyse systemic risk in the core global banking system using a new network-based spectral eigen-pair method, which treats network failure as a dynamical system stability problem. This is compared with market price-based Systemic Risk Indexes, viz. Marginal Expected Shortfall, Delta Conditional Value-at-Risk, and Conditional Capital Shortfall Measure of Systemic Risk in a cross-border setting. Unlike paradoxical market price based risk measures, which underestimate risk during periods of asset price booms, the eigen-pair method based on bilateral balance sheet data gives early-warning of instability in terms of the tipping point that is analogous to the R number in epidemic models. For this regulatory capital thresholds are used. Furthermore, network centrality measures identify systemically important and vulnerable banking systems. Market price-based SRIs are contemporaneous with the crisis and they are found to covary with risk measures like VaR and betas

Schizophrenia and the Scaffolded Self

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this recordA family of recent externalist approaches in philosophy of mind argues that our psychological capacities are synchronically and diachronically “scaffolded” by external (i.e., beyond-the-brain) resources. Despite much interest in this topic, however, it has not found its way to philosophy of psychiatry in a substantive way. I here consider how these “scaffolded” approaches to mind and self might inform debates in phenomenological psychopathology. First, I introduce the idea of “affective scaffolding”. I distinguish three forms of affective scaffolding and support this taxonomy by appealing to different sources of empirical work. Second, I put the idea of affective scaffolding to work. Using schizophrenia as a case study, I argue — along with others in phenomenological psychopathology — that schizophrenia is fundamentally a self-disturbance. However, I offer a subtle reconfiguration of these approaches. I argue that schizophrenia is not simply a disruption of ipseity or minimal self-consciousness but rather a disruption of the scaffolded self, established and regulated via its ongoing engagement with the world and others. I conclude that this way of thinking about the scaffolded self is potentially transformative both for our theoretical as well as practical understanding of the causes and character of schizophrenic experience, insofar as it suggests the need to consider new forms of intervention and treatment

Comparative constructions of similarity in Northern Samoyedic languages

The purpose of this paper is to analyze the suffixes which are used in Northern Samoyedic languages to build comparative constructions of equality. Depending on the language, the suffixes may perform three functions: word-building, form-building, and inflectional. When they mark the noun, they serve as simulative suffixes and are employed to build object comparison. In the inflectional function, these suffixes mark the verb and are a means of constructing situational comparison. In this case, they signal the formation of a special mood termed the Approximative. This paper provides a detailed description of the Approximative from paradigmatic and syntagmatic perspectives

Neurotrophins and psychiatric disorders

Increasing number of studies has during the last decade linked neurotrophic factors with the pathophysiology of neuropsychiatric disorders and with the mechanisms of action of drugs used for the treatment of these disorders. In particular, brain-derived neurotrophic factor BDNF and its receptor TrkB have been connected with the pathophysiology in mood disorders and there is strong evidence that BDNF signaling is critically involved in the recovery from depression with both pharmacological and psychological means. Neurotrophins play a central role in neuronal plasticity and network connectivity in developing and adult brain and recent evidence links plasticity and network rewiring with mood disorders and their treatment. Therefore, neurotrophins should not be seen as happiness factors, but as critical tools in the process where brain networks are optimally tuned to environment and it is against this background that the effects of neurotrophins on neuropsychiatric disorders should be looked at.Peer reviewe