Inhibition of CREB Activity in the Dorsal Portion of the Striatum Potentiates Behavioral Responses to Drugs of Abuse

The striatum participates in multiple forms of behavioral adaptation, including habit formation, other forms of procedural memory, and short- and long-term responses to drugs of abuse. The cyclic-AMP response element binding protein (CREB) family of transcription factors has been implicated in various forms of behavioral plasticity, but its role in the dorsal portion of the striatum-has been little explored. We previously showed that in transgenic mice in which CREB function is inhibited in the dorsal striatum, bidirectional synaptic plasticity and certain forms of long-term procedural memory are impaired. Here we show, in startling contrast, that inhibition of striatal CREB facilitates cocaine- and morphine-place conditioning and enhances locomotor sensitization to cocaine. These findings propose CREB as a positive regulator of dorsal striatum-dependent procedural learning but a negative regulator of drug-related learning

PSO-based tuning of MURAME parameters for creditworthiness evaluation of Italian SMEs

In this work we use a MultiCriteria Decision Analysis (MCDA) model to evalu- ate the creditworthiness of a sample of Italian Small and Medium-sized Enterprises (SMEs), on the basis of their balance sheet data provided by the AIDA database. Our methodology is able to consider simultaneously different factors affecting the firms’ solvency level, and can produce results in terms of scoring, classification into homogeneous rating classes and migration probabilities. In this contribution we compare the results obtained considering two scenarios. On one hand, we experience an exogenous specification of the parameters that describe the preference structure implicit in the used MCDA model. On the other hand, we consider the results obtained using a preference disaggregation method to endogenously determine some of the model parameters. Because of the complexity of the obtained math- ematical programming problem, we use an heuristic methodology, namely Particle Swarm Optimization (PSO), which provides a reasonable compromise between the quality of the solution and the computational burden

"Sequencing-grade" screening for BRCA1 variants by oligo-arrays

The need for fast, efficient, and less costly means to screen genetic variants associated with disease predisposition led us to develop an oligo-nucleotide array-based process for gene-specific single nucleotide polymorphism (SNP) genotyping. This cost-effective, high-throughput strategy has high sensitivity and the same degree of accuracy as direct sequencing, the current gold standard for genetic screening. We used the BRCA1 breast and ovarian cancer predisposing gene model for the validation of the accuracy and efficiency of our strategy. This process could detect point mutations, insertions or deletions of any length, of known and unknown variants even in heterozygous conditions without affecting sensitivity and specificity. The system could be applied to other disorders and can also be custom-designed to include a number of genes related to specific clinical conditions. This system is particularly useful for the screening of long genomic regions with relatively infrequent but clinically relevant variants, while drastically cutting time and costs in comparison to high-throughput sequencing

MATHEMATICAL METHODS IN ECONOMICS AND FINANCE

Mathematical Methods in Economics and Finance is a journal published by the Ca' Foscari Department of Economics since 2012, and formerly published by the Department of Applied Mathematics of the same University from 2006 to 2011. This journal replaces the former Rendiconti, a series in Italian issued annually from 1969 to 2005. The main features of the journal are: 1. Publication of original and unpublished papers that present theoretical results, methodological contributions, and applications in the areas of actuarial mathematics, financial mathematics, management science, mathematical economics, quantitative finance, and operational research. 2. Peer review process based on double-blind refereeing by at least two anonymous referees. 3. Inclusion in the MathSciNet list of journals. 4. Published papers online are free to access and download

MATHEMATICAL METHODS IN ECONOMICS AND FINANCE

This is the special issue of Mathematical Methods in Economics and Finance devoted to the International Scientific Forum “Education and Entrepreneurship in Siberia: directions of Cooperation and Development of Regions” held in Novosibirsk (Russia) from October 12 to 13, 2018. The Forum was dedicated to the 50th anniversary of Novosibirsk State University of Economics and Managements. The purpose of the Forum was to contribute to the formation of a scientific environment that (1) stimulates research into the application of business-oriented educational technologies, taking into account regional development strategies; (2) creates favorable conditions for interdisciplinary studies of organizational, technological, institutional and behavioral factors in the functioning of the entrepreneurial university and training of business engineers. Mathematical Methods in Economics and Finance is a journal published by the Ca' Foscari Department of Economics since 2012, and formerly published by the Department of Applied Mathematics of the same University from 2006 to 2011. This journal replaces the former Rendiconti, a series in Italian issued annually from 1969 to 2005. The main features of the journal are: 1. Publication of original and unpublished papers that present theoretical results, methodological contributions, and applications in the areas of actuarial mathematics, financial mathematics, management science, mathematical economics, quantitative finance, and operational research. 2. Peer review process based on double-blind refereeing by at least two anonymous referees. 3. Inclusion in the MathSciNet list of journals and in the ANVUR (National Agency for the Evaluation of Universities and Research Institutes) list of journals. 4. Published papers online are free to access and download

Mice lacking Ras-GRF1 show contextual fear conditioning but not spatial memory impairments: convergent evidence from two independently generated mouse mutant lines

Ras-GRF1 is a neuronal specific guanine exchange factor that, once activated by both ionotropic and metabotropic neurotransmitter receptors, can stimulate Ras proteins, leading to long-term phosphorylation of downstream signaling. The two available reports on the behavior of two independently generated Ras-GRF1 deficient mouse lines provide contrasting evidence on the role of Ras-GRF1 in spatial memory and contextual fear conditioning. These discrepancies may be due to the distinct alterations introduced in the mouse genome by gene targeting in the two lines that could differentially affect expression of nearby genes located in the imprinted region containing the Ras-grf1 locus. In order to determine the real contribution of Ras-GRF1 to spatial memory we compared in Morris Water Maze learning Brambilla’s mice with a third mouse line (GENA53) in which a non-sense mutation was introduced in the Ras-GRF1 coding region without additional changes in the genome and we found that memory in this task is normal. Also, we measured both contextual and cued fear conditioning, which were previously reported to be affected in Brambilla’s mice, and we confirmed that contextual learning but not cued conditioning is impaired in both mouse lines. In addition, we also tested both lines for the first time in conditioned place aversion in the Intellicage, an ecological and remotely controlled behavioral test, and we observed normal learning. Finally, based on previous reports of other mutant lines suggesting that Ras-GRF1 may control body weight, we also measured this non-cognitive phenotype and we confirmed that both Ras-GRF1 deficient mutants are smaller than their control littermates. In conclusion, we demonstrate that Ras-GRF1 has no unique role in spatial memory while its function in contextual fear conditioning is likely to be due not only to its involvement in amygdala functions but possibly to some distinct hippocampal connections specific to contextual learning

Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice

The striatum has a well documented role in procedural learning and memory. However, the synaptic and molecular mechanisms of acquisition and storage of this form of memory remain poorly understood. We examined procedural memory and plasticity in transgenic mice reversibly expressing a dominant-negative cAMP response element-binding protein (CREB) mutant in the dorsal striatum. In these transgenic mice, corticostriatal long-term potentiation and depression are abolished, indicating that CREB function is essential for bidirectional long-term synaptic plasticity in this structure. Importantly, CREB-deficient animals show reversible alterations in several forms of striatum-dependent memory, including footshock avoidance learning and "response" learning in the cross maze. These findings implicate transcriptional regulation by CREB family transcription factors in striatum-dependent information processing and provide the first clear correlation between procedural learning and memory and synaptic plasticity at the corticostriatal synapse

Intracranial Hemorrhage from Dural Arteriovenous Fistulas: What Can We Find with CT Angiography?

Background: Dural arteriovenous fistulas (DAVF) represent a rare acquired intracranial vascular malformation, with a variety of clinical signs and symptoms, which make their diagnosis difficult. Intracranial hemorrhage is one of the most serious clinical manifestations. In this paper the authors’ goal was to verify the accuracy and utility of contrast-enhanced brain CT angiography (CTA) for the identification and the characterization of dural arteriovenous fistulas (DAVFs) in patients who presented with brain hemorrhage compared to 3D digital subtraction angiography (3D DSA); (2) a retrospective study of 26 patients with DAVFs who presented with intracranial hemorrhage to our institution was performed. The information reviewed included clinical presentation, location and size of hemorrhage, brain CTA and 3D DSA findings; (3) results: 61% (16/26) of DAVFs were identified by CTA. The vast majority of patients were male (69%, 18/26) and the most common presenting symptom was sudden onset headache. All DAVFs had cortical venous drainage and about one-third were associated with a venous varix. The most common location was tentorial (73%, 19/26); (4) conclusions: CTA can represent a valid alternative diagnostic method to 3D DSA for the study of DAVF in the initial and preliminary diagnostic approach, especially in emergency situations. In fact, it represents a fast, inexpensive, non-invasive and above all, easily accessible and available diagnostic technique, unlike DSA or MRI, allowing to provide information necessary for the identification, classification and treatment planning of DAVF

Aquaporin-9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells

Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an “immature” to a “mature” state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis