Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Characterization of USH1C/harmonin in the human retina provides insights into pathophysiology and therapy options for Usher syndrome Usher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retina uncovered harmonin a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Muller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones, and outer segments of rods as well as at adhesive junctions of MGCs and photoreceptors in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in MGCs and photoreceptors and rhodopsin in photoreceptors. Subcellular expression and colocalization of harmonin correlates with the clinical phenotype observed in USH1C patients. In addition, primary cilia defects in USH1C patient-derived fibroblasts could be reverted by delivery of harmonin a1 transcript isoform. Our data provide novel insights into photoreceptor cell biology, USH1C pathophysiology and for developing gene therapy treatment.
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The categories of this paper are: plant
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The categories of this paper are: cell
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The categories of this paper are: education
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The categories of this paper are: communication
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The categories of this paper are: synthetic
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The categories of this paper are: microbiology
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The categories of this paper are: systems
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The categories of this paper are: scientific
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The categories of this paper are: zoology
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The categories of this paper are: pathology
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The categories of this paper are: neuroscience
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The categories of this paper are: biochemistry
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The categories of this paper are: animal
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The categories of this paper are: cancer
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The categories of this paper are: developmental
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The categories of this paper are: behavior