Sox10 is a high mobility group (HMG) domain transcription factor which is an important regulator for neural crest development. SOX10 mutations have been identified in Waardenburg-Shah syndrome type 4 (WS4) patients who suffer from sensorineural deafness. However, the mechanisms underlying the hearing defect of SOX10-mediated WS4 are unclear. The aim of this study is to elucidate the function of Sox10 during mouse inner ear development using a mutant mouse model, in order to reveal the underlying basis for SOX10 mutation associated sensorineural deafness in WS4 patients. The mammalian inner ear originates from the otic placode epithelium as well as neural crest cells (NCCs). To understand the role of Sox10 in inner development, I investigated the contribution of cranial NCCs to the cochleovestibular ganglion (CVG) by lineage tracing analysis, using Wnt1-cre;ZEG mice in which all NCCs were marked by GFP. Co-expression of GFP-positive cells with the glial marker BFABP suggested that glial cells in the CVG were derived from NCCs. Furthermore, Sox10-expressing NCCs were found to invade the CVG at 30-somite stage. These results suggest a role of Sox10 in regulating cranial NCCs contribution to CVG glia. In our laboratory we have generated a mouse mutant Sox10EGFP in which the Sox10 N-terminal domain was fused to the EGFP reporter. To investigate the function of Sox10 in NCCs invasion and gliogenesis of CVG, phenotypic analysis of Sox10NGFP mutant mouse were performed. EGFP expression in the CVG and inner ear epithelium of Sox10NGFP/+ embryos recapitulated the dynamic expression pattern of Sox10. Sox10NGFP/NGFP mutants displayed a reduced number of migrating NCCs and lacked NCCs or glia in their CVG. Moreover, loss of glial cell in the developing spiral ganglia of Sox10NGFP/NGFP mice led to disorganized fasciculation and degeneration of axonal filaments. These data suggest that Sox10 is required for maintaining the cranial NC stem cell pool, and is also essential for CVG gliogenesis and normal growth and innervation of spiral ganglion neurons. To study the function of Sox10 in regulating cochlear morphogenesis, morphological and histological analysis of mutant cochlear were performed. As illustrated by paint-filling analysis, Sox10NGFP/NGFP mice developed a shortened cochlear duct, reduced cochlear turning and enlarged endolymph lumen. Sensory hair cell patterning in the organ of Corti was normal in the Sox10 mutant as shown by immunohistochemistry analysis, suggesting that cochlear lumen enlargement was not due to disrupted planar cell polarity (PCP) pathway. To explore the molecular basis of Sox10-mediated cochlear morphogenic defect, expression of genes related to cochlear development were examined by qRT-PCR. Candidate genes included those involved in fluid homeostasis, which are known to affect the size of cochlear lumen. Up-regulated expression of Aquaporin 3, a water channel protein in the cochlear epithelium that facilitates water transport across the cell membrane, was observed in Sox10NGFP/NGFP cochlear. These results suggest that Sox10 may regulate cochlear morphogenesis by controlling endolymph homeostasis. In conclusion, Sox10 is required in multiple processes during inner ear development including NCC invasion, gliogenesis and cochlear morphogenesis, and their abnormal development can lead to sensorineural deafness in WS4 syndrome. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

abstract / Biochemistry / Master / Master of Philosophy

Background: To date, there is a lack of research that has focused on the needs of late cochlear implanted adults with prelingual deafness. The specific study aims were: (1) to explore the met and unmet long-term needs of late cochlear implanted adults with prelingual deafness from their own perspectives and those of the employees at SCIP; and 2) to identify a consensus of the most important met and unmet long-term needs of late cochlear implanted adults with prelingual deafness. Method: This study used a modified Delphi technique with two rounds. In the first round, nine adults who were considered experts on this topic participated in semi-structured in-depth interviews. The participants were five late cochlear implanted recipients with prelingual deafness who were involved in the Southern Cochlear Implant Programme in New Zealand, and four clinicians from the programme. The interview transcripts were analysed using qualitative content analysis. The results from the first round were used to inform the development of the survey for the second round. The second round of the study involved surveying the same participants who participated in the first round. These surveys were quantitatively analysed so as to discover which needs were considered important and met, and important and unmet for the cochlear implant recipients, from the perspectives of the two categories of participants. Results: The first round of the study revealed 42 met needs and 39 unmet needs that fell into 15 categories. Of these needs, 26 met needs and 18 unmet needs were identified as being important by a majority of the participants in the second round. Conclusion: The results from the study may impact potential CI recipients’ and their families’ expectations of what the device can provide, as well as the development of future services and governmental policies in the area.

Tyrimo tikslas - įvertinti klausos negalią turinčių sportuojančių ir nesportuojančių vyrų psichomotorinės reakcijos ir hemodinamikos rodiklius, priklausomai nuo fizinio krūvio bei kurtumo pobūdžio. Tyrimo hipotezė - įvertinus sportuojančių ir nesportuojančių vyrų su klausos negalia psichomotorinės reakcijos rodiklius po fizinio krūvio mėginio, reakcijos laikas nesportuojančių grupėje bus ilgesnis, o lyginant pagal kurtumo pobūdį, sportuojančių asmenų, turinčių įgytą kurtumą, reakcijos laikas bus trumpesnis. Tyrimo uždaviniai: 1. Įvertinti sportuojančių vyrų su klausos negalia, paprastosios ir sudėtingosios reakcijos laikus prieš ir po krūvio mėginio ir palyginti su nesportuojančių vyrų, turinčių klausos negalią, rodikliais. 2. Nustatyti klausos negalią turinčių sportuojančių vyrų psichomotorinės paprastosios ir sudėtingosios reakcijos laiką, priklausomai nuo kurtumo pobūdžio prieš ir po krūvio mėginio. 3. Įvertinti klausos negalią turinčių sportuojančių vyrų hemodinamikos rodiklių (dvigubos sandaugos), paprastosios ir sudėtingos reakcijos pokyčius, taikant 6 minučių ėjimo testą, priklausomai nuo kurtumo pobūdžio. Tyrimo metodika. Tyrime dalyvavo 22 jauno amžiaus kurtumo negalią turintys vyrai. Tiriamąją grupę sudarė kurčiųjų krepšinio rinktinės žaidėjai (amžius 23,80±2,6 metai), (45,5 proc., n=10), kontrolinę grupę – nesportuojantys, kurtumo negalią turintys vyrai (amžius 21,75±1,8 metai), (54,5 proc., n=12). Tyrimai buvo atlikti LSU Judesių valdymo laboratorijoje naudojant... [toliau žr. visą tekstą] / The aim of the study was – to evaluate psychomotor reactions and hemodynamic indices of sporstmen with hearing impairment and male persons who did not go in for sport. Hypothesis – The time of psychomotor reaction comparing sporstmen and people who do not do sports with hearing impairment subject to physical strain the time will be longer of those who do not go in for sport. And according deafness nature the reaction time will be longer in the group of sporstmen subject to acquired deafness nature. Objectives of the study: 1. To evaluate the time of simple and complex reaction before and after strain sample of sportsmen with hearing impairment and people who do not do sports with hearing impairment. 2. To estimate psychomotoric simple and complex reaction time of sportsmen with hearing impairment, subject to deafness nature before and after strain sample. 3. To evaluate hemodynamic parameters (double product) simple and complex reaction change of sportsmen with hearing impairment invoking 6 min. walking test subject to deafness nature. Research methods. Twenty two young people with hearing impairment took part in the study. There were deaf national basketball team players in the searching group (age 23,80±2,6), (45,5%., n=10), People with hearing impairment who do not go in for sport were in a control group (age 21,75±1,8 ), (54,5%., n=12). Researches were made in Lithuanian sports university (LSU) using analyser (DPA – 1) (p. No. 5251; 2005 08 25) of human hands and... [to full text]

Doctor of Philosophy (PhD) / An in-depth, longitudinal study of the speech and oral language development of eight infants with a profound hearing loss who receive early interventions focused on developing their auditory, speech and oral language capacity is presented in this thesis. Infants were tracked for two years, during the period when they are changed from a hearing aid to a cochlear implant. All infants in this study had their hearing loss identified early and were fitted with hearing aids between 1 and 7 months of age and received their cochlear implant between 8 and 16 months of age. They attended a number of different auditory-verbal early intervention programs (depending on where they lived) all of which focused on developing speech and language skills through listening. Attendance at their particular early intervention program at least once a week was in addition to weekly attendance the Sydney Cochlear Implant Centre for therapy and audiological services. A broad range of measures has been used to track the infants’ acquisition of oral language skills, including measures of communicative intention, pre-speech and speech development, and oral language development. Despite a wide range of individual differences across the group of infants, the results suggest some general trends. In the area of communicative intent most infants followed typical development patterns in terms of both the types (e.g. requesting, answering etc) and forms (gestural, vocal, verbal) used, but they showed delays in their frequency of usage of these types and forms. For speech development the infants demonstrated typical speech skills by 18-months post-cochlear implantation in the areas of consonant inventories, severity of phonological involvement (speech intelligibility) and phonological process development, but they showed delays in vowel and consonant acquisition. Finally, for language development the infants were delayed relative to typical development at 18 months post-implantation. The findings support and extend previous studies which have demonstrated the benefits of early intervention for communication development in infants with hearing loss (Calderon & Naidu, 2000; Mayne, Yoshinaga-Itano & Sedey, 2000; Moeller, 2000; Yoshinaga-Itano & Apuzzo, 1998). However, the delays in the oral communication skills of the infants in the current study suggest that more intensive long-term intervention is required if the infants are to attain typical oral speech and language development. The findings capture the complexity of early oral language development, which has been lacking in previous studies of infants with significant hearing loss, receiving a cochlear implant (Dettman, Briggs, & Dowell, 2005; Houston, Ying, Pisoni, & Iler Kirk, 2003; Schauwers, Gillis, Daemers, De Beukelaer, & Govaerts, 2004). The present data also provide some limited support for earlier implantation, that is, before 12 months of age, as the infants made little progress in oral language development while using hearing aids. The reduced amount of auditory signal available to them prior to implantation may be the determining factor in their inability to follow typical rates and patterns of development. However, rates of development with the implant were not straightforward and further research on this population is needed. Universal neonatal screening programs for hearing loss will potentially provide a larger population of early identified infant for future research. This will create the opportunity for large scale, prospective, longitudinal, studies examining the acquisition of speech and oral language development. Limitations of this study, tracking the early stages of speech and language development over a two year period are identified. Future studies are needed to follow the infants for a longer time to determine if their rate of development is sufficient for them to catch up in areas of delay and maintain their performance in areas where they match their typically developing peers.

Thesis (Ph.D.)--University of Melbourne, Dept. of Otolaryngology, 2007. / Typescript. Includes bibliographical references (leaves 210-221).

Thesis (M. Sc.) -- University College London, 1998. / A project submitted (to the Institute of Laryngology and Otology) as a requirement for the degree of Master of Science in Audiological Medicine, University College London. Bibliography: leaves 83-101.

Thesis (D. Phil. Communication Pathology)--University of Pretoria, 2003. / Summary in English and Afrikaans. Includes bibliographical references.

Thesis (Ph. D.)--University of California, San Diego, 2004. / Vita. Includes bibliographical references (leaves 297-312).

Thesis (M. Ed.)--York University, 2003. Graduate Programme in Education. / Typescript. Name on certificate page : P. Lynn Caruso. Includes bibliographical references (leaves 130-140). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ82910.