Browsing by Author "Tekinay, Ayşe Begüm"
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Item Open Access Homozygosity mapping and targeted genomic sequencing reveal the game responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred(Cold Spring Harbor Laboratory Press, 2011) Gulsuner, Süleyman; Tekinay, Ayşe Begüm; Doerschner, Katja; Boyaci, Hüseyin; Bilguvar, K.; Ünal, Hilal; Örs, Aslıhan; Onat, O. Emre; Atalar, Ergin; Basak, A. N.; Topaloglu, H.; Kansu, T.; Tan, M.; Tan, U.; Gunel, M.; Özçelik, TayfunThe biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.Item Open Access Neuroactive peptide nanofibers for regeneration of spinal cord after injury(Wiley-VCH Verlag GmbH & Co. KGaA, 2020-10-11) Sever-Bahçekapılı, Melike; Yılmaz, Canelif; Demirel, A.; Kilinc, M. C.; Dogan, I.; Caglar, Y. S.; Guler, M. O.; Tekinay, Ayşe BegümThe highly complex nature of spinal cord injuries (SCIs) requires design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Promising SCI treatments use biomaterial scaffolds, which provide bioactive cues to the cells in order to trigger neural regeneration in the spinal cord. In this work, the use of peptide nanofibers is demonstrated, presenting protein binding and cellular adhesion epitopes in a rat model of SCI. The self-assembling peptide molecules are designed to form nanofibers, which display heparan sulfate mimetic and laminin mimetic epitopes to the cells in the spinal cord. These neuroactive nanofibers are found to support adhesion and viability of dorsal root ganglion neurons as well as neurite outgrowth in vitro and enhance tissue integrity after 6 weeks of injury in vivo. Treatment with the peptide nanofiber scaffolds also show significant behavioral improvement. These results demonstrate that it is possible to facilitate regeneration especially in the white matter of the spinal cord, which is usually damaged during the accidents using bioactive 3D nanostructures displaying high densities of laminin and heparan sulfate-mimetic epitopes on their surfaces.