Loss of the miR379-410 cluster in mice leads to alterations in social and anxiety-related behaviours

microRNAs (miRNAs) belong to a group of small non-coding RNAs that down regulates gene expression at the post-transcriptional level. The paternally imprinted placental mammal-specific miR379-410 cluster hosts 38 miRNAs. In the last decade, several members of the cluster have been shown to regulate synapse development and plasticity in mammals. Further, they have been implicated in a variety of diseases, including neurodevelopmental disorders. However, the potential involvement of these miRNAs in the control of complex behaviour in mammals, such as sociability, remains largely unknown. This is an important issue since aberrant synaptic dysfunction is thought to underlie neurodevelopmental diseases, such as autism spectrum disorder (ASD), characterized by deficits in social communication and interaction as well as restricted repetitive behaviour. This study aimed at the characterization of a constitutive knock-out (ko) mouse model that carries a deletion of the miR379-410 cluster. Extensive behavioural assays across the animals’ lifespan and cellular examinations of structural and functional properties of synapses were performed. Furthermore, transcriptome sequencing of adult miR379-410 ko hippocampi allowed the validation of potential direct target candidates of the miRNA cluster by using molecular and biochemical approaches. Mice deficient for the miR379-410 cluster displayed an anti-autistic-like phenotype, consisting of hypersocial behaviour, increased ultrasonic vocalizations (USVs) and reduced repetitive behaviour in the absence of cognitive impairments. Further, miR379-410 ko mice presented an anxiety phenotype over the lifespan. Along with the behavioural phenotype, miR379-410 ko mice showed increased excitatory synaptic transmission and spine density accompanied by an elevated expression of ionotropic glutamate receptor complex components in the hippocampus. Several of these components, identified by transcriptome profiling (Cnih2, Src, Prr7 and Dlgap3) could be validated as direct miR379-410 target genes. Taken together, the data obtained in this thesis describe for the first time a negative regulatory role of the miR379-410 cluster in social behaviour and the control of genes associated with excitatory synaptic function. Thus, interfering with miRNAs from the miR379-410 cluster could represent in the future a promising strategy for the treatment of neurodevelopmental disorders characterized by social dysfunction, such as ASD

NASA's Microgravity Technology Report, 1996: Summary of Activities

This report covers technology development and technology transfer activities within the Microgravity Science Research Programs during FY 1996. It also describes the recent major tasks under the Advanced Technology Development (ATD) Program and identifies current technology requirements. This document is consistent with NASA,s Enteprise for the Human Exploration and development of Space (HEDS) Strategic Plan. This annual update reflects changes in the Microgravity Science Research Program's new technology activities and requirements. Appendix A. FY 1996 Advanced Technology Development. Program and Project Descriptions. Appendix B. Technology Development

Quantitative Performance Assessment of LiDAR-based Vehicle Contour Estimation Algorithms for Integrated Vehicle Safety Applications

Many nations and organizations are committing to achieving the goal of `Vision Zero\u27 and eliminate road traffic related deaths around the world. Industry continues to develop integrated safety systems to make vehicles safer, smarter and more capable in safety critical scenarios. Passive safety systems are now focusing on pre-crash deployment of restraint systems to better protect vehicle passengers. Current commonly used bounding box methods for shape estimation of crash partners lack the fidelity required for edge case collision detection and advanced crash modeling. This research presents a novel algorithm for robust and accurate contour estimation of opposing vehicles. The presented method is evaluated via a developed framework for key performance metrics and compared to alternative algorithms found in literature

Estimation of a Coronary Vessel Wall Deformation with High-Frequency Ultrasound Elastography

Elastography, which is based on applying pressure and estimating the resulting deformation, involves the forward problem to obtain the strain distributions and inverse problem to construct the elastic distributions consistent with the obtained strains on observation points. This thesis focuses on the former problem whose solution is used as an input to the latter problem. The aim is to provide the inverse problem community with accurate strain estimates of a coronary artery vessel wall. In doing so, a new ultrasonic image-based elastography approach is developed. Because the accuracy and quality of the estimated strain fields depend on the resolution level of the ultrasound image and to date best resolution levels obtained in the literature are not enough to clearly see all boundaries of the artery, one of the main goals is to acquire high-resolution coronary vessel wall ultrasound images at different pressures. For this purpose, first an experimental setup is designed to collect radio frequency (RF) signals, and then image formation algorithm is developed to obtain ultrasound images from the collected signals. To segment the noisy ultrasound images formed, a geodesic active contour-based segmentation algorithm with a novel stopping function that includes local phase of the image is developed. Then, region-based information is added to make the segmentation more robust to noise. Finally, elliptical deformable template is applied so that a priori information regarding the shape of the arteries could be taken into account, resulting in more stable and accurate results. The use of this template also implicitly provides boundary point correspondences from which high-resolution, size-independent, non-rigid and local strain fields of the coronary vessel wall are obtained.Ph.D.Committee Chair: Benkeser, Paul; Committee Member: Koblasz, Arthur; Committee Member: Skrinjar, Oskar; Committee Member: Vidakovic, Brani; Committee Member: Yezzi, Anthon

Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism

Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4–22 (Δe4–22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4–22−/− mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs

Point-of-Care Ultrasound: New Concepts and Future Trends

Ultrasound (US) technology, with major advances and new developments, has become an essential and first-line imaging modality for clinical diagnosis and interventional treatment. US imaging has evolved from one-dimensional, twodimensional to three-dimensional display, and from static to real-time imaging, as well as from structural to functional imaging. Based on its portability and advanced digital imaging technique, US was first adopted by emergency medicine in the 1980s and gradually gained popularity among other specialists for clinical diagnosis and interventional treatment. Point-of-Care Ultrasound (POCUS) was then proposed as a new concept and developed for new uses, which greatly extended clinical US applications. Nowadays, artificial intelligence (AI), cloud computing, 5G network, robotics, and remote technologies are starting to be integrated into US equipment. US systems have gradually evolved to an intelligent terminal platform with powerful imaging and communication tools. In addition, specialized US machines tend to be more suitable and important to meet increasing demands and requirements by various clinical specialties and departments. In this article, we review current US technology and POCUS as new concepts and its future trends, as well as related technological developments and clinical applications