PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Bi-Allelic Variants in OLA1 Cause a Neurodevelopmental Disorder with Joint Hypermobility(Cell Press, 2026-04) Cevik, Sebiha; Alzahrani, Fatema; Sezer, Abdullah; AlAbdi, Lama; Demir, Zanyar; Abdullah, Nor Linda; Alkuraya, Fowzan S.Cytoskeletal organization, cell adhesion, and cell motility are key to neuronal development and functional synapses. Obg-like ATPase 1 (OLA1) regulates cell-matrix adhesion by modulating focal adhesion kinase (FAK) levels, therefore regulating cytoskeletal dynamics and cell motility. To date, however, no Mendelian phenotypes in humans have been linked to OLA1. We identified fourteen individuals from nine families in whom hypermobility-neurodevelopmental disorder with distinct facies is linked to bi-allelic deleterious variants in OLA1. The hypermobility phenotype evoked a diagnosis of Ehlers-Danlos syndrome (EDS) in some affected individuals. The loss-of-function nature of these variants is confirmed in proband-derived fibroblasts, recapitulating the impaired migration and proliferation phenotype previously described in OLA1-deficient cells. To explore the pathogenesis of abnormal neurodevelopment in our probands, we investigated neurons derived from proband fibroblasts and identified impaired adhesion and cytoskeletal control. Modeling ola-1 deficiency in C. elegans revealed reduced neurite numbers compared to the wild type. Additionally, transcriptomic analysis of the ola-1-deficient worms suggested that dysregulation of key signaling pathways results in suppression of microtubule dynamics and axon regrowth, ultimately crippling the regenerative competence of mutant animals compared to wild-type controls. Our results support an autosomal-recessive OLA1-related hypermobility-neurodevelopmental disorder and suggest that dysregulation of key signaling pathways results in the suppression of microtubule dynamics as a potential underlying mechanism.Article Citation - WoS: 28Citation - Scopus: 34Micro- and Nanodevices Integrated With Biomolecular Probes(Pergamon-Elsevier Science Ltd, 2015-12) Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A.Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. (C) 2015 Elsevier Inc. All rights reserved.