Models of <i>KPTN</i>-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.</p

The Castle District of Budapest : Housing Before and After War and Revolution

Color poster with text, maps, table, and photos.The goal of this research was to study the changes in buildings and streets in the Castle District of Budapest.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

1848 Obuda : A Social Portrait From a Forgotten Census

Color poster with text, map, images, and tables.The purpose of this study is to analyze the 1848 census that was taken in Obuda, a northern suburb of Budapest. This project is important because this is the first time that this census has been totaled and analyzed.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

An Interdisciplinary Approach to the Urban Streetscape of Budapest's Andrassy Ut

As Budapest's most prominent boulevard, Andrassy Ut (Andrassy Way) exhibits a variety of urban land uses designed to showcase Hungarian history and culture and provide modern housing and leisure amenities for the city's elite. Designed and constructed in the 1870s, it is anchored in by Erzsebet tor (Erzsebet Square) in the city center and extends 2.42 km (1.5 mi) northeast to Varosliget (City Park). This study, conducted in summer 2014 by students in UW-Eau Claire's interdisciplinary Central European Travel Seminar (CETS), examined the cultural streetscape of the boulevard through the lens of geography, history, and music. Teams of researchers were dispatched to designated stretches of Andrassy Ut to document the ways in which historically and musically significant buildings and institutions coincide with high-end residential and commercial land uses. Landscape analysis was then utilized to document concentrations of specific types of land uses. As the city embarks on a massive redevelopment project that will convert Andrassy Ut from mixed use corridor into the tourism-focused Andrassy Quarter, this study marks an important transition period in the boulevard's history