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Primary ciliary dyskinesia (PCD, OMIM 244400) is a rare genetic disorder that affects motile cilia and is characterised by impaired mucociliary clearance of the airway epithelium, which results in chronic upper and lower airway infections. While short-read next-generation sequencing technology has been used for the genetic testing of PCD, its effectiveness is limited in identifying variants in the gene because of the nearly identical pseudogene As we confirmed that the gene was not expressed in airway cells, we obtained nasal mucosa biopsy specimens for total RNA sequencing (RNA-seq) with library enrichment using exome oligos. Among the 34 nasal samples from patients suspected of having PCD, three aberrant splicing patterns in were identified in two samples.
View Article and Find Full Text PDFMotile cilia modulate neuronal and astroglial activity in the zebrafish larval brain.
Cell Rep
January 2025
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons Gate 1, 7491 Trondheim, Norway; Kavli Institute for Systems Neuroscience and Centre for Algorithms in the Cortex, Norwegian University of Science and Technology, Olav Kyrres Gate 9, 7030 Trondheim, Norway. Electronic address:
The brain uses a specialized system to transport cerebrospinal fluid (CSF), consisting of interconnected ventricles lined by motile ciliated ependymal cells. These cells act jointly with CSF secretion and cardiac pressure gradients to regulate CSF dynamics. To date, the link between cilia-mediated CSF flow and brain function is poorly understood.
View Article and Find Full Text PDFOptical Methods for Determining the Phagocytic Activity Profile of CD206-Positive Macrophages Extracted from Bronchoalveolar Lavage by Specific Mannosylated Polymeric Ligands.
Polymers (Basel)
December 2024
Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, 119991 Moscow, Russia.
Macrophage (Mph) polarization and functional activity play an important role in the development of inflammatory lung conditions. The previously widely used bimodal classification of Mph into M1 and M2 does not adequately reflect the full range of changes in polarization and functional diversity observed in Mph in response to various stimuli and disease states. Here, we have developed a model for the direct assessment of Mph from bronchial alveolar lavage fluid (BALF) functional alterations, in terms of phagocytosis activity, depending on external stimuli, such as exposure to a range of bacteria (, and ).
View Article and Find Full Text PDFValosin-containing protein p97 extracts capping protein CP110 from the mother centriole to promote ciliogenesis.
Mol Biol Cell
January 2025
Dept. of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198.
The primary cilium is a crucial signaling organelle that can be generated by most human cells, and impediments to primary ciliogenesis lead to a variety of developmental disorders known as ciliopathies. The removal of the capping protein, CP110, from the mother centriole is a crucial early step that promotes generation of the ciliary vesicle and ciliogenesis. Recent studies have demonstrated that CP110 undergoes polyubiquitination and degradation in the proteosome, but the mechanisms of unfolding and removal from the mother centriole remain unknown.
View Article and Find Full Text PDFRegulation of INPP5E in Ciliogenesis, Development, and Disease.
Int J Biol Sci
January 2025
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.
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