Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

An hybrid methodology for RL-based behavior coordination in a target following mission with an AUV

Proposes a behavior-based scheme for high-level control of autonomous underwater vehicles (AUVs). Two main characteristics can be highlighted in the control scheme. Behavior coordination is done through a hybrid methodology, which takes in advantages of the robustness and modularity in competitive approaches, as well as optimized trajectories

Digital beamforming and moving target indication for future spaceborne synthetic aperture radar

During the last decade the interest on space-borne Synthetic Aperture Radars (SAR) for remote sensing applications has grown as testified by the number of recent and forthcoming missions as TerraSAR-X, RADARSAT-2, COSMO-kyMed, TanDEM-X and the Spanish SEOSAR/PAZ. In this sense, this thesis proposes to study and analyze the performance of the state-of-the-Art space-borne SAR systems, with modes able to provide Moving Target Indication capabilities (MTI), i.e. moving object detection and estimation. The research will focus on the MTI processing techniques as well as the architecture and/ or configuration of the SAR instrument, setting the limitations of the current systems with MTI capabilities, and proposing efficient solutions for the future missions. Two European projects, to which the Universitat Politècnica de Catalunya provides support, are an excellent framework for the research activities suggested in this thesis. NEWA project proposes a potential European space-borne radar system with MTI capabilities in order to fulfill the upcoming European security policies. This thesis will critically review the state-of-the-Art MTI processing techniques as well as the readiness and maturity level of the developed capabilities. For each one of the techniques a performance analysis will be carried out based on the available technologies, deriving a roadmap and identifying the different technological gaps. In line with this study a simulator tool will be developed in order to validate and evaluate different MTI techniques in the basis of a flexible space-borne radar configuration. The calibration of a SAR system is mandatory for the accurate formation of the SAR images and turns to be critical in the advanced operation modes as MTI. In this sense, the SEOSAR/PAZ project proposes the study and estimation of the radiometric budget. This thesis will also focus on an exhaustive analysis of the radiometric budget considering the current calibration concepts and their possible limitations. In the framework of this project a key point will be the study of the Dual Receive Antenna (DRA) mode, which provides MTI capabilities to the mission. An additional aspect under study is the applicability of the Digital Beamforming on multichannel and/or multistatic radar platforms, which conform potential solutions for the NEWA project with the aim to fully exploit its capability jointly with MTI techniques.

Derivatives of the Antimicrobial Peptide BP100 for Expression in Plant Systems

Production of antimicrobial peptides in plants constitutes an approach for obtaining them in high amounts. However, their heterologous expression in a practical and efficient manner demands some structural requirements such as a minimum size, the incorporation of retention signals to assure their accumulation in specific tissues, and the presence of protease cleavage amino acids and of target sequences to facilitate peptide detection. Since any sequence modification may influence the biological activity, peptides that will be obtained from the expression must be screened prior to the synthesis of the genes for plant transformation. We report herein a strategy for the modification of the antimicrobial undecapeptide BP100 that allowed the identification of analogues that can be expressed in plants and exhibit optimum biological properties. We prepared 40 analogues obtained by incorporating repeated units of the antimicrobial undecapeptide, fragments of natural peptides, one or two AGPA hinges, a Gly or Ser residue at the N-terminus, and a KDEL fragment and/or the epitope tag54 at the C-terminus. Their antimicrobial, hemolytic and phytotoxic activities, and protease susceptibility were evaluated. Best sequences contained a magainin fragment linked to the antimicrobial undecapeptide through an AGPA hinge. Moreover, since the presence of a KDEL unit or of tag54 did not influence significantly the biological activity, these moieties can be introduced when designing compounds to be retained in the endoplasmic reticulum and detected using a complementary epitope. These findings may contribute to the design of peptides to be expressed in plants