Large-scale neuroanatomical study uncovers 198 gene associations in mouse brain morphogenesis.

Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here we analyze 118 neuroanatomical parameters in 1,566 mutant mouse lines and identify 198 genes whose disruptions yield NeuroAnatomical Phenotypes (NAPs), mostly affecting structures implicated in brain connectivity. Groups of functionally similar NAP genes participate in pathways involving the cytoskeleton, the cell cycle and the synapse, display distinct fetal and postnatal brain expression dynamics and importantly, their disruption can yield convergent phenotypic patterns. 17% of human unique orthologues of mouse NAP genes are known loci for cognitive dysfunction. The remaining 83% constitute a vast pool of genes newly implicated in brain architecture, providing the largest study of mouse NAP genes and pathways. This offers a complementary resource to human genetic studies and predict that many more genes could be involved in mammalian brain morphogenesis

Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein

Background Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus. Results We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic cells, yet its function is not understood. Here, we find MVP expression highly specific to the limbic system and show that Mvp regulates neuronal morphology, postnatally and specifically in males. We also recapitulate a previously reported genetic interaction and show that Mvp+/−;Mapk3+/− mice exhibit behavioral deficits, notably decreased anxiety-like traits detected in the elevated plus maze and open field paradigms. Conclusions Our study highlights multiple gene drivers in neuroanatomical phenotypes, interacting with each other through complex relationships. It also provides the first evidence for the involvement of the major vault protein in the regulation of brain size and neuroanatomy, specifically in male mice

Cybersecurity Standard Compliance in Development of Distributed Embedded Systems

In recent years, communication technologies have been actively developed and used in the machinery manufacturing industry. They allow distributed embedded systems to operate more efficiently by remotely interacting with each other and with maintenance systems. However, the ability of machines to communicate through the Internet has increased the number of attack vectors that a potential attacker can utilize. In the lift industry, cybersecurity incidents can lead to a malfunction of lift systems, disruptions to transportation services and irreparable damage to people's lives. The manufacturer can implement security measures from industrial cybersecurity standards to prevent cybersecurity incidents that involve the developed products, to improve security of industrial systems and to ensure safety of their users. Nonetheless, the cybersecurity standards compliance process can be challenging for the product developers. Our intention is to apply this process to the development of distributed embedded systems. In this thesis project, we conducted research on the cybersecurity standards of the IEC 62443 series that are applicable in the lift industry. We analyzed ISO 8102-20 that was published in August 2022 to cover cybersecurity for lifts. We also applied this standard to the development of a prototype of a lift controller in a case study. We document the process of applying ISO 8102-20, present insights into the new standard and underline some areas for improvement

Working with formulaic language as a way to evaluate and improve EFL non-linguistics students' pragmatic skills in a culture-specific contextual situation

AbstractThe present article considers the learners’ ability to understand and use formulaic language as an indicator of their pragmatic skills. Experimental data has been collected and analyzed to identify the current level of the learners’ pragmatic skills and to reveal problems they face in culture-specific communicative situations. Classroom activities for developing pragmatic skills have been suggested

Characterization of Two Mouse Chd7 Heterozygous Loss-of-Function Models Shows Dysgenesis of the Corpus Callosum and Previously Unreported Features of CHARGE Syndrome.

CHARGE syndrome is a rare congenital disorder frequently caused by mutations in the chromodomain helicase DNA-binding protein-7 CHD7. Here, we developed and systematically characterized two genetic mouse models with identical, heterozygous loss-of-function mutation of the Chd7 gene engineered on inbred and outbred genetic backgrounds. We found that both models showed consistent phenotypes with the core clinical manifestations seen in CHARGE syndrome, but the phenotypes in the inbred Chd7 model were more severe, sometimes having reduced penetrance and included dysgenesis of the corpus callosum, hypoplasia of the hippocampus, abnormal retrosplenial granular cortex, ventriculomegaly, hyperactivity, growth delays, impaired grip strength and repetitive behaviors. Interestingly, we also identified previously unreported features including reduced levels of basal insulin and reduced blood lipids. We suggest that the phenotypic variation reported in individuals diagnosed with CHARGE syndrome is likely due to the genetic background and modifiers. Finally, our study provides a valuable resource, making it possible for mouse biologists interested in Chd7 to make informed choices on which mouse model they should use to study phenotypes of interest and investigate in more depth the underlying cellular and molecular mechanisms