Key Gene Network Related to Primary Ciliary Dyskinesia in Hippocampus of Patients with Alzheimer’S Disease Revealed by Weighted Gene Co-Expression Network Analysis

Background. Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main organs involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little knowledge is known on its association with primary ciliary dyskinesia (PCD). Material and Methods. The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network. Results. Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients. Conclusion. Our study demonstrated that AD and PCD have shared metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD. Subjects Bioinformatics, Cell Biology, Molecular Biology, Neurology

Key Gene Network Related to Primary Ciliary Dyskinesia in Hippocampus of Patients With Alzheimer’s Disease Revealed by Weighted Gene Co-expression Network Analysis

Background. Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main organs involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little knowledge is known on its association with primary ciliary dyskinesia (PCD).Material and Methods. The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network.Results. Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g.,DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients.Conclusion. Our study demonstrated that AD and PCD have shared metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD.Subjects Bioinformatics, Cell Biology, Molecular Biology, Neurology

Mucociliary Respiratory Epithelium Integrity in Molecular Defense and Susceptibility to Pulmonary Viral Infections

Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fitness. The concerted action of ciliary movement on the respiratory epithelial surface and the pathogen entrapment function of mucus help to maintain healthy airways. Consequently, genetic or acquired defects in lung defense elicit respiratory diseases and secondary microbial infections that inflict damage on pulmonary function and may even be fatal. Individuals living with chronic and acute respiratory diseases are more susceptible to develop severe coronavirus disease-19 (COVID-19) illness and hence should be proficiently managed. In light of the prevailing pandemic, we review the current understanding of the respiratory system and its molecular components with a major focus on the pathophysiology arising due to collapsed respiratory epithelium integrity such as abnormal ciliary movement, cilia loss and dysfunction, ciliated cell destruction, and changes in mucus rheology. The review includes protein interaction networks of coronavirus infection-manifested implications on the molecular machinery that regulates mucociliary clearance. We also provide an insight into the alteration of the transcriptional networks of genes in the nasopharynx associated with the mucociliary clearance apparatus in humans upon infection by severe acute respiratory syndrome coronavirus-2.

The design of an inner-motile waste-energy-driven piezoelectric catalytic system

Inspired by the microorganisms in nature, a new type of waste-energy-driven catalytic film is explored firstly by using magnetically actuated artificial cilia. Due to its singular characteristic of ciliary movement,...

Two novel mutations in the DNAH11 gene in primary ciliary dyskinesia (CILD7) with considerable variety in the clinical and beating cilia phenotype

Background Diagnosis of primary ciliary dyskinesia (PCD) still remains a challenge, especially with mutations in the Dynein Arm Heavy Chain 11 (DNAH11) gene. Classical diagnostic measures like Transmission Electron Microscopy (TEM) are not applicable for mutations in the DNAH11 gene since ultrastructural defects of the ciliary apparatus are absent. Novel mutations encoding for PCD appear all the time with considerable variation in the clinical picture, making it necessary to update data bases and guidelines for PCD diagnostics. Methods In this study we examined two unrelated, Finnish families with symptoms of PCD applying the clinical scoring system: Primary ciliary dyskinesia Rule (PICADAR), high speed video microscopy analysis (HSVMA) for ciliary movement, a commercially available gene panel analysis and nasal Nitric Oxide (nNO) measurements if applicable. Results Two, likely pathogenic variants in the DNAH11 gene (c.2341G > A, p. (Glu781Lys) ja c.7645 + 5G > A) were detected. In the first family, compound heterozygous mutations led to disease manifestation in two of 4 children, which showed a similar phenotype of cilia beating pattern but marked differences in disease severity. In the second family, all three children were homozygotes for the c.2341G > A p.(Glu781Lys) mutation and showed a similar degree of disease severity. However, the phenotype of cilia beating pattern was different ranging from stiff, static cilia to a hyperkinetic movement in one of these children. Conclusions In this study we describe two Finnish families with PCD, revealing two novel mutations in the DNAH11 gene which show considerable variety in the clinical and beating cilia phenotype. The results of this study show the clinician that PCD can be much milder than generally expected and diagnosis demands a combination of measures which are only successful in experienced hands. Chronic and repeatedly treated wet cough should raise suspicion of PCD, referring the patient for further diagnostics to a specialised PCD centre.

Total Intravenous Anesthesia for Immobile Cilia Syndrome. About a Case

Immotile cilia syndrome is an autosomal recessive disorder which is characterized by ciliary dysfunction and decreased mucociliary clearance. This ciliary function is a mechanism whose primary pulmonary defense alteration can be a problem during inhalational anesthesia, as these cause decreased ciliary movement. However during total intravenous anesthesia this normal ciliary movement can be preserved using remifentanil and propofol. A case of immotile cilia syndrome was handled with complete intravenous anesthesia for surgery protocol type ovarian handling post-operative pain epidural catheter is presented.

How signals of calcium ions initiate the beats of cilia and flagella

ABSTRACTCilia and flagella are cell organelles serving basic roles in cellular motility. Ciliary movement is performed by a sweeping-like repeated bending motion, which gives rise to a self-propagating “ciliary beat”. The hallmark structure in cilia is the axoneme, a stable architecture of microtubule doublets. The motion of axoneme is powered by the axonemal dynein motor family powered by ATP hydrolysis. It is still unclear how the organized beat of cilium and flagella emerges from the combined action of hundreds of dynein molecules. It has been hypothesized that such coordination is mediated by mechanical stress due to transverse, radial or sliding deformations. The beating asymmetry is crucial for airway ciliary function and it requires tubulin glutamination a unique posttranslational modification of C-termini of constituent microtubules that is highly abundant in cilia and flagella. The exact role of tubulin glutamination in ciliary or flagellar function is still unclear. Here we examine the role of calcium (Ca2+) ions based on the experimental evidences that the flagellar asymmetry can be increased due to the entry of extracellular Ca2+through, for example, nimodipine-sensitive pathway located in the flagella. We propose a new scenario based on the polyelectrolyte properties of cellular microtubules (MTs) such that dynamic influx of Ca2+ions provides the initiation and synchronization of dynein sliding along microtubules. We also point out the possible interplay between tubulin polyglutaminated C-termini and localized pulses of Ca2+ions along microtubules.