Comparison of the gene expression profiles of human fetal cortical astrocytes with pluripotent stem cell derived neural stem cells identifies human astrocyte markers and signaling pathways and transcription factors active in human astrocytes

Astrocytes are the most abundant cell type in the central nervous system (CNS) and have a multitude of functions that include maintenance of CNS homeostasis, trophic support of neurons, detoxification, and immune surveillance. It has only recently been appreciated that astrocyte dysfunction is a primary cause of many neurological disorders. Despite their importance in disease very little is known about global gene expression for human astrocytes. We have performed a microarray expression analysis of human fetal astrocytes to identify genes and signaling pathways that are important for astrocyte development and maintenance. Our analysis confirmed that the fetal astrocytes express high levels of the core astrocyte marker GFAP and the transcription factors from the NFI family which have been shown to play important roles in astrocyte development. A group of novel markers were identified that distinguish fetal astrocytes from pluripotent stem cell-derived neural stem cells (NSCs) and NSC-derived neurons. As in murine astrocytes, the Notch signaling pathway appears to be particularly important for cell fate decisions between the astrocyte and neuronal lineages in human astrocytes. These findings unveil the repertoire of genes expressed in human astrocytes and serve as a basis for further studies to better understand astrocyte biology, especially as it relates to disease.published_or_final_versio

Automatic Rating of Hoarseness by Text-based Cepstral and Prosodic Evaluation

The standard for the analysis of distorted voices is perceptual rating of read-out texts or spontaneous speech. Automatic voice evaluation, however, is usually done on stable sections of sustained vowels. In this paper, text-based and established vowel-based analysis are compared with respect to their ability to measure hoarseness and its subclasses. 73 hoarse patients (48.3±16.8 years) uttered the vowel /e/ and read the German version of the text “The North Wind and the Sun”. Five speech therapists and physicians rated roughness, breathiness, and hoarseness according to the German RBH evaluation scheme. The best human-machine correlations were obtained for measures based on the Cepstral Peak Prominence (CPP; up to |r | = 0.73). Support Vector Regression (SVR) on CPP-based measures and prosodic features improved the results further to r ≈0.8 and confirmed that automatic voice evaluation should be performed on a text recording

Laryngeal Reinnervation Using Ansa Cervicalis for Thyroid Surgery-Related Unilateral Vocal Fold Paralysis: A Long-Term Outcome Analysis of 237 Cases

To evaluate the long-term efficacy of delayed laryngeal reinnervation using the main branch of the ansa cervicalis in treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery.UVFP remains a serious complication of thyroid surgery. Up to now, a completely satisfactory surgical treatment of UVFP has been elusive.From Jan. 1996 to Jan. 2008, a total of 237 UVFP patients who underwent ansa cervicalis main branch-to-recurrent laryngeal nerve (RLN) anastomosis were enrolled as UVFP group; another 237 age- and gender-matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and electromyography were performed preoperatively and postoperatively. The mean follow-up period was 5.2±2.7 years, ranging from 2 to 12 years.>0.05, respectively). Postoperative laryngeal electromyography confirmed successful reinnervation of laryngeal muscle.Delayed laryngeal reinnervation with the main branch of ansa cervicalis is a feasible and effective approach for treatment of thyroid surgery-related UVFP; it can restore the physiological laryngeal phonatory function to the normal or a nearly normal voice quality

Pediatric cochlear implantation: an update

Deafness in pediatric age can adversely impact language acquisition as well as educational and social-emotional development. Once diagnosed, hearing loss should be rehabilitated early; the goal is to provide the child with maximum access to the acoustic features of speech within a listening range that is safe and comfortable. In presence of severe to profound deafness, benefit from auditory amplification cannot be enough to allow a proper language development. Cochlear implants are partially implantable electronic devices designed to provide profoundly deafened patients with hearing sensitivity within the speech range. Since their introduction more than 30 years ago, cochlear implants have improved their performance to the extent that are now considered to be standard of care in the treatment of children with severe to profound deafness. Over the years patient candidacy has been expanded and the criteria for implantation continue to evolve within the paediatric population. The minimum age for implantation has progressively reduced; it has been recognized that implantation at a very early age (12–18 months) provides children with the best outcomes, taking advantage of sensitive periods of auditory development. Bilateral implantation offers a better sound localization, as well as a superior ability to understand speech in noisy environments than unilateral cochlear implant. Deafened children with special clinical situations, including inner ear malformation, cochlear nerve deficiency, cochlear ossification, and additional disabilities can be successfully treated, even thogh they require an individualized candidacy evaluation and a complex post-implantation rehabilitation. Benefits from cochlear implantation include not only better abilities to hear and to develop speech and language skills, but also improved academic attainment, improved quality of life, and better employment status. Cochlear implants permit deaf people to hear, but they have a long way to go before their performance being comparable to that of the intact human ear; researchers are looking for more sophisticated speech processing strategies as well as a more efficient coupling between the electrodes and the cochlear nerve with the goal of dramatically improving the quality of sound of the next generation of implants

Gene Therapy Restores Auditory and Vestibular Function in a Mouse Model of Usher Syndrome Type 1c

Because there are currently no biological treatments for deafness, we sought to advance gene therapy approaches to treat genetic deafness. We reasoned that gene delivery systems that target auditory and vestibular sensory cells with high efficiency would be required to restore complex auditory and balance function. We focused on Usher Syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and used a knock-in mouse model, Ush1c c.216G>A, which carries a cryptic splice site mutation found in French-Acadian patients with Usher Syndrome type IC (USH1C). Following delivery of wild-type Ush1c into the inner ears of neonatal Ush1c c.216G>A mice, we find recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders

Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons

α-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons

Morphologic Differences in the Vocal Tract Resonance Cavities of Voice Professionals: An MRI-Based Study

The processes that take place during singing and acting are complex. However, morphologic and dynamic studies of the vocal tracts during speech have been gaining greater attention, mainly because of the rapid technical advances being made with magnetic resonance imaging (MRI) and image analysis and processing techniques. Objectives/Hypothesis and Methods Our aim was to describe the morphologic differences in the vocal tract resonance cavities among voice professionals using MRI, and with the three-dimensional models built from the MRI data, compare the volumes calculated for the whole vocal tract and its major resonance cavities. Study Design Prospective study. Results The images acquired during the spoken and singing tasks provided morphologic information about the whole vocal tract cavity and also its two major resonance cavities: the oral and the pharynx cavities; differences were observed in the volumes measured during the production of some vowels. Conclusions The morphologic differences found in the singing voices indicated an increase in the oral cavity volume, resulting in an increase in the overall volumes measured. In the acting voices, both the resonance cavities of the vocal tract contributed to the differences measured.info:eu-repo/semantics/publishedVersio