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1

Hoque, Mohammed, Danny Chen, Rex A. Hess, Feng-Qian Li, and Ken-Ichi Takemaru. "CEP164 is essential for efferent duct multiciliogenesis and male fertility." Reproduction 162, no. 2 (August 1, 2021): 129–39. http://dx.doi.org/10.1530/rep-21-0042.

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Cilia are evolutionarily conserved microtubule-based structures that perform diverse biological functions. Cilia are assembled on basal bodies and anchored to the plasma membrane via distal appendages. In the male reproductive tract, multicilia in efferent ducts (EDs) move in a whip-like motion to prevent sperm agglutination. Previously, we demonstrated that the distal appendage protein CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and ciliogenesis. Mice lacking CEP164 in multiciliated cells (MCCs) (FoxJ1-Cre;CEP164fl/fl) show a significant loss of multicilia in the trachea, oviduct, and ependyma. In addition, we observed male sterility; however, the precise role of CEP164 in male fertility remained unknown. Here, we report that the seminiferous tubules and rete testis of FoxJ1-Cre;CEP164fl/fl mice exhibit substantial dilation, indicative of dysfunctional multicilia in the EDs. We found that multicilia were hardly detectable in the EDs of FoxJ1-Cre;CEP164fl/fl mice although FoxJ1-positive immature cells were present. Sperm aggregation and agglutination were commonly noticeable in the lumen of the seminiferous tubules and EDs of FoxJ1-Cre;CEP164fl/fl mice. In FoxJ1-Cre;CEP164fl/fl mice, the apical localization of Cby1 and the transition zone marker NPHP1 was severely diminished, suggesting basal body docking defects. TEM analysis of EDs further confirmed basal body accumulation in the cytoplasm of MCCs. Collectively, we conclude that male infertility in FoxJ1-Cre;CEP164fl/fl mice is caused by sperm agglutination and obstruction of EDs due to loss of multicilia. Our study, therefore, unravels an essential role of the distal appendage protein CEP164 in male fertility.
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2

Hoque, Mohammed, Eunice N. Kim, Danny Chen, Feng-Qian Li, and Ken-Ichi Takemaru. "Essential Roles of Efferent Duct Multicilia in Male Fertility." Cells 11, no. 3 (January 20, 2022): 341. http://dx.doi.org/10.3390/cells11030341.

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Cilia are microtubule-based hair-like organelles on the cell surface. Cilia have been implicated in various biological processes ranging from mechanosensation to fluid movement. Ciliary dysfunction leads to a plethora of human diseases, known as ciliopathies. Although non-motile primary cilia are ubiquitous, motile multicilia are found in restricted locations of the body, such as the respiratory tract, the oviduct, the efferent duct, and the brain ventricles. Multicilia beat in a whip-like motion to generate fluid flow over the apical surface of an epithelium. The concerted ciliary motion provides the driving force critical for clearing airway mucus and debris, transporting ova from the ovary to the uterus, maintaining sperm in suspension, and circulating cerebrospinal fluid in the brain. In the male reproductive tract, multiciliated cells (MCCs) were first described in the mid-1800s, but their importance in male fertility remained elusive until recently. MCCs exist in the efferent ducts, which are small, highly convoluted tubules that connect the testis to the epididymis and play an essential role in male fertility. In this review, we will introduce multiciliogenesis, discuss mouse models of male infertility with defective multicilia, and summarize our current knowledge on the biological function of multicilia in the male reproductive tract.
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Nikolaev, Sergey I., Cédric Berney, Nikolai B. Petrov, Alexandre P. Mylnikov, José F. Fahrni, and Jan Pawlowski. "Phylogenetic position of Multicilia marina and the evolution of Amoebozoa." International Journal of Systematic and Evolutionary Microbiology 56, no. 6 (June 1, 2006): 1449–58. http://dx.doi.org/10.1099/ijs.0.63763-0.

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Recent molecular phylogenetic studies have led to the erection of the phylum Amoebozoa, uniting naked and testate lobose amoebae, the mycetozoan slime moulds and amitochondriate amoeboid protists (Archamoebae). Molecular data together with ultrastructural evidence have suggested a close relationship between Mycetozoa and Archamoebae, classified together in the Conosea, which was named after the cone of microtubules that, when present, is characteristic of their kinetids. However, the relationships of conoseans to other amoebozoans remain unclear. Here, we obtained the complete small-subunit (SSU) rRNA gene sequence (2746 bp) of the enigmatic, multiflagellated protist Multicilia marina, which has formerly been classified either in a distinct phylum, Multiflagellata, or among lobose amoebae. Our study clearly shows that Multicilia marina belongs to the Amoebozoa. Phylogenetic analyses including 60 amoebozoan SSU rRNA gene sequences revealed that Multicilia marina branches at the base of the Conosea, together with another flagellated amoebozoan, Phalansterium solitarium, as well as with Gephyramoeba sp., Filamoeba nolandi and two unidentified amoebae. This is the first report showing strong support for a clade containing all flagellated amoebozoans and we discuss the position of the root of the phylum Amoebozoa in the light of this result.
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4

Gueron, Shay, and Nadav Liron. "Ciliary motion modeling, and dynamic multicilia interactions." Biophysical Journal 63, no. 4 (October 1992): 1045–58. http://dx.doi.org/10.1016/s0006-3495(92)81683-1.

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5

Saito, Hiroko, Fumiko Matsukawa-Usami, Toshihiko Fujimori, Toshiya Kimura, Takahiro Ide, Takaki Yamamoto, Tatsuo Shibata, et al. "Tracheal motile cilia in mice require CAMSAP3 for the formation of central microtubule pair and coordinated beating." Molecular Biology of the Cell 32, no. 20 (October 1, 2021): ar12. http://dx.doi.org/10.1091/mbc.e21-06-0303.

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CAMSAP3, a protein that controls microtubule dynamics by binding to its minus-end, is localized at proximal regions of the axoneme in tracheal motile cilia. Its dysfunction results in a collapse of the central microtube pair, basal plate disorganization, and uncoordinated beating of multicilia.
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6

Pathak, Narendra, Christina A. Austin-Tse, Yan Liu, Aleksandr Vasilyev, and Iain A. Drummond. "Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function." Molecular Biology of the Cell 25, no. 12 (June 15, 2014): 1836–44. http://dx.doi.org/10.1091/mbc.e13-01-0033.

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Glutamylation is a functionally important tubulin posttranslational modification enriched on stable microtubules of neuronal axons, mitotic spindles, centrioles, and cilia. In vertebrates, balanced activities of tubulin glutamyl ligase and cytoplasmic carboxypeptidase deglutamylase enzymes maintain organelle- and cell type–specific tubulin glutamylation patterns. Tubulin glutamylation in cilia is regulated via restricted subcellular localization or expression of tubulin glutamyl ligases (ttlls) and nonenzymatic proteins, including the zebrafish TPR repeat protein Fleer/Ift70. Here we analyze the expression patterns of ccp deglutamylase genes during zebrafish development and the effects of ccp gene knockdown on cilia formation, morphology, and tubulin glutamylation. The deglutamylases ccp2, ccp5, and ccp6 are expressed in ciliated cells, whereas ccp1 expression is restricted to the nervous system. Only ccp5 knockdown increases cilia tubulin glutamylation, induces ciliopathy phenotypes, including axis curvature, hydrocephalus, and pronephric cysts, and disrupts multicilia motility, suggesting that Ccp5 is the principal tubulin deglutamylase that maintains functional levels of cilia tubulin glutamylation. The ability of ccp5 knockdown to restore cilia tubulin glutamylation in fleer/ift70 mutants and rescue pronephric multicilia formation in both fleer- and ift88-deficient zebrafish indicates that tubulin glutamylation is a key driver of ciliogenesis.
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7

Yan, Xiumin, Huijie Zhao, and Xueliang Zhu. "Production of Basal Bodies in bulk for dense multicilia formation." F1000Research 5 (June 28, 2016): 1533. http://dx.doi.org/10.12688/f1000research.8469.1.

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Centriole number is normally under tight control and is directly linked to ciliogenesis. In cells that use centrosomes as mitotic spindle poles, one pre-existing mother centriole is allowed to duplicate only one daughter centriole per cell cycle. In multiciliated cells, however, many centrioles are generated to serve as basal bodies of the cilia. Although deuterosomes were observed more than 40 years ago using electron microscopy and are believed to produce most of the basal bodies in a mother centriole-independent manner, the underlying molecular mechanisms have remained unknown until recently. From these findings arise more questions and a call for clarifications that will require multidisciplinary efforts.
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8

Matsuo, Moe, Atsuko Shimada, Sumito Koshida, Yumiko Saga, and Hiroyuki Takeda. "The establishment of rotational polarity in the airway and ependymal cilia: analysis with a novel cilium motility mutant mouse." American Journal of Physiology-Lung Cellular and Molecular Physiology 304, no. 11 (June 1, 2013): L736—L745. http://dx.doi.org/10.1152/ajplung.00425.2012.

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The airway is covered by multicilia that beat in a metachronous manner toward the mouth to eliminate debris and infectious particles. Coordinated one-directional beating is an essential feature of multicilia in the airway to guarantee proper mucociliary clearance. Defects in ciliary motility lead to primary ciliary dyskinesia (PCD), with major symptoms including bronchitis and other chronic respiratory diseases. Recent work suggested that ciliary motility and planar polarity are required in the process of ciliary alignment that produces coordinated beating. However, the extent to which cilia motility is involved in this process in mammals has not yet been fully clarified. Here, to address the role of ciliary motility in the process of coordinated ciliary alignment, we analyzed Kintoun mice mutants ( Ktu−/−). Ktu−/− exhibited typical phenotypes of PCD with complete loss of ciliary motility in trachea and another ciliated tissue, the brain ependyma. Immunohistochemistry using antibodies against axonemal dynein confirmed the loss of multiple axonemal dynein components in mutant cilia. Observation of cilia orientation based on basal foot directions revealed that ciliary motility was not required in the alignment of airway cilia, whereas a strong requirement was observed in brain ependymal cells. Thus we conclude that the involvement of ciliary motility in the establishment of coordinated ciliary alignment varies among tissues.
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9

Stubbs, J. L., E. K. Vladar, J. D. Axelrod, and C. Kintner. "Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation." Nature Cell Biology 14, no. 2 (January 8, 2012): 140–47. http://dx.doi.org/10.1038/ncb2406.

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10

Mikrjukov, Kirill A., and Alexander P. Mylnikov. "The fine structure of a carnivorous multiflagellar protist Multicilia marina Cienkowski, 1881 (flagellata incertae sedis)." European Journal of Protistology 34, no. 4 (December 1998): 391–401. http://dx.doi.org/10.1016/s0932-4739(98)80008-4.

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11

Otto, Tobias, Sheyla V. Candido, Mary S. Pilarz, Ewa Sicinska, Roderick T. Bronson, Michaela Bowden, Iga A. Lachowicz, et al. "Cell cycle-targeting microRNAs promote differentiation by enforcing cell-cycle exit." Proceedings of the National Academy of Sciences 114, no. 40 (September 18, 2017): 10660–65. http://dx.doi.org/10.1073/pnas.1702914114.

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MicroRNAs (miRNAs) have been known to affect various biological processes by repressing expression of specific genes. Here we describe an essential function of the miR-34/449 family during differentiation of epithelial cells. We found that miR-34/449 suppresses the cell-cycle machinery in vivo and promotes cell-cycle exit, thereby allowing epithelial cell differentiation. Constitutive ablation of all six members of this miRNA family causes derepression of multiple cell cycle-promoting proteins, thereby preventing epithelial cells from exiting the cell cycle and entering a quiescent state. As a result, formation of motile multicilia is strongly inhibited in several tissues such as the respiratory epithelium and the fallopian tube. Consequently, mice lacking miR-34/449 display infertility as well as severe chronic airway disease leading to postnatal death. These results demonstrate that miRNA-mediated repression of the cell cycle is required to allow epithelial cell differentiation.
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12

Jomantiene, Rasa, Robert E. Davis, Ellen L. Dally, John L. Maas, and Joseph D. Postman. "The Distinctive Morphology of `Fragaria multicipita' Is Due to Phytoplasma." HortScience 33, no. 6 (October 1998): 1069–72. http://dx.doi.org/10.21273/hortsci.33.6.1069.

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The rare plant, Fragaria multicipita Fern., was characterized by an unusual vegetative morphology that was long presumed to be suggestive of an ice front relict. While an additional species of Fragaria would be a potential source of genetic diversity for enhancing cultivated strawberry germplasm, evidence now indicates that such potential is not present in F. multicipita. Grafting of F. multicipita to F. chiloensis Duchesne resulted in transmission of a subgroup 16SrVI-B phytoplasma to, and the development of multicipital growth in, F. chiloensis. The results indicated that F. multicipita is a phytoplasma-diseased aberrant growth form of F. virginiana Duchesne and is an unfounded taxon. It is apparent that this plant population offers no unique potential for increasing genetic diversity in cultivated strawberry germplasm, but the phytoplasma may be capable of infecting commercial strawberry.
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13

Ma, L., I. Quigley, H. Omran, and C. Kintner. "Multicilin drives centriole biogenesis via E2f proteins." Genes & Development 28, no. 13 (June 16, 2014): 1461–71. http://dx.doi.org/10.1101/gad.243832.114.

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14

Balestra, Fernando R., and Pierre Gönczy. "Multiciliogenesis: Multicilin Directs Transcriptional Activation of Centriole Formation." Current Biology 24, no. 16 (August 2014): R746—R749. http://dx.doi.org/10.1016/j.cub.2014.07.006.

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15

Postman, Joseph D., and Paul M. Catling. "FRAGARIA MULTICIPITA - A PATHOGEN INDUCED TAXON." Acta Horticulturae, no. 471 (November 1998): 31–34. http://dx.doi.org/10.17660/actahortic.1998.471.2.

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16

Wan, Kirsty Y., and Rebecca N. Poon. "Mechanisms and functions of multiciliary coordination." Current Opinion in Cell Biology 86 (February 2024): 102286. http://dx.doi.org/10.1016/j.ceb.2023.102286.

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17

Yang, Xingzhou, Robert H. Dillon, and Lisa J. Fauci. "An Integrative Computational Model of Multiciliary Beating." Bulletin of Mathematical Biology 70, no. 4 (January 31, 2008): 1192–215. http://dx.doi.org/10.1007/s11538-008-9296-3.

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18

Dillon, R. H., L. J. Fauci, and Xingzhou Yang. "Sperm Motility and Multiciliary Beating: An Integrative Mechanical Model." Computers & Mathematics with Applications 52, no. 5 (September 2006): 749–58. http://dx.doi.org/10.1016/j.camwa.2006.10.012.

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19

Rohde, K., and N. Watson. "Paired multiciliate receptor complexes in larvalMulticotyle purvisi (Trematoda, Aspidogastrea)." Parasitology Research 76, no. 7 (1990): 597–601. http://dx.doi.org/10.1007/bf00932569.

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20

AKYÜZ, Enes, Ekin Emre ERKILIÇ, Mustafa Reha COŞKUN, Oğuz MERHAN, Umut BATI, Mert SEZER, and Emre BAHÇİVAN. "Pasteuralla multicida kaynaklı pnömonili koyunlarda enrofloksasin ve tulatromisin tedavilerinin karşılaştırılması." Journal of Advances in VetBio Science and Techniques 7, no. 2 (August 31, 2022): 242–49. http://dx.doi.org/10.31797/vetbio.1124136.

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In this study, it was aimed to compare the treatments of enrofloxacin and tulatromycin in sheep with pneumonia caused by Pasteuralla multicida. A total of 45 female Tuj sheep between the ages of 2-6 were used in the study. Group 1 enrofloxacin administered 15 sheep, group 2 tulatromycin administered 15 sheep, and 15 healthy sheep of the same age group and characteristics formed the control group. Bronchoalveolar lavage fluid samples were obtained from sheep with clinical signs (cough, purulent, serous, mucopurulent nasal discharge) of respiratory system disease. After the microbiological examination of the samples taken, those positive for Pasteuralla multicida were included in the study. Blood samples (10 mL) from the Vena jugularis were collected in serum tubes with K2EDTA and gel from the sick animals before and after the treatment as well as once from the control group. In our study, rectal temperature, respirations per minute and pulse rates before treatment were found to be statistically significantly higher in patient groups compared to the control group (P<0.001). Total leukocyte count was found to be higher in the patient groups before treatment compared to the control group (P=0.010). Among the biochemical parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and creatine kinase levels were found to be statistically significantly higher in the patient groups compared to the control group before treatment (P<0.05). Clinical improvement was observed from the 3th day in group 2 and from the 5th day in group 1. As a result, administration of a single dose of tulatromycin resulted in earlier clinical improvement than administration of enrofloxacin for one week. At the same time, it was concluded that tulatromycin is more beneficial and practical in terms of a single application.
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21

GAO, TAIPING, DONG REN, and CHUNGKUN SHIH. "Abrotoxyela gen. nov. (Insecta, Hymenoptera, Xyelidae) from the Middle Jurassic of Inner Mongolia, China." Zootaxa 2094, no. 1 (May 8, 2009): 52–59. http://dx.doi.org/10.11646/zootaxa.2094.1.6.

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Abrotoxyela gen. nov. of Xyelidae and Abrotoxyela lepida sp. nov. and Abrotoxyela multiciliata sp. nov. are described from the Middle Jurassic Jiulongshan Formation of Daohugou Village, Inner Mongolia, China. The new genus is established on basis of the triple-branched vein Sc of the fore wing with first branch intersecting C at nearly 1/4 of its length; Sc terminates at C distal to the origin of Rs; and basal section of Rs approximately as long as that of M.
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22

Wheatley, Denys N., and Samuel S. Bowser. "Length control of primary cilia: analysis of monociliate and multiciliate PtK1 cells." Biology of the Cell 92, no. 8-9 (December 2000): 573–82. http://dx.doi.org/10.1016/s0248-4900(00)01108-4.

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23

Rohde, K., and P. R. Garlick. "A multiciliate ‘starcell’ in the parenchyma of the larva of Austramphilina elongata (Amphilinidea)." International Journal for Parasitology 15, no. 4 (August 1985): 403–7. http://dx.doi.org/10.1016/0020-7519(85)90025-6.

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24

Suryadi, Jendi, Muhammad Arief, and Winoto Winoto. "Multimedia Audio Visual And Broadcasting Bagian Detik TV PT. Agranet Multicitra Siberkom Jakarta Selatan." CICES 3, no. 2 (August 31, 2017): 231–39. http://dx.doi.org/10.33050/cices.v3i2.462.

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The rapid development of technology in the current era of globalization makes a handful of people need to get more information, in order to add insight. No doubt the need for information becomes a necessity. News is an information about the occurrence of an event or event. Its development through radio broadcasting, print media, television broadcasting and online media. Online news broadcasting is a package that must be packaged well and good for people who watch it get the latest and actual information. An online news broadcasting package includes activities to be Reporter, Editing related to production and packaging in News delivery in PT. AGRANET MULTICITRA SIBERKOM (detikcom).
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25

Muniardiningrum, Gita, and Trinandari Prasetya Nugrahanti. "Analisa implementasi PSAK 24 Revisi 2013 dalam meningkatkan kepuasan karyawan pada PT. Agranet Multicitra Siberkom." Jurnal Riset Perbankan, Manajemen, dan Akuntansi 3, no. 1 (January 8, 2019): 68. http://dx.doi.org/10.56174/jrpma.v3i1.40.

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This study aims to: a) Know and analyze the calculation of PSAK 24 Revision 2013 in the short-term employment benefits, Post-employment, other long-term employee benefits and severance pay; b) Know and analyze the implementation of PSAK 24 Revision 2013 in return for employee satisfaction at PT. AgranetMulticitraSiberkom.The approach used in this research is qualitative approach, while the research method using descriptive method. The research technique is interview and observation on HRD and Accounting Division of PT. AgranetMulticitraSiberkom in Jakarta. Keywords: PSAK 24 Revision 2013, Financial Accounting Standards, Employee Benefits, Employee Satisfaction.
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26

Davis, Robert E., Rasa Jomantiene, Audrone Kalvelyte, and Ellen L. Dally. "Differential amplification of sequence heterogeneous ribosomal RNA genes and classification of the ‘Fragaria multicipita’ phytoplasma." Microbiological Research 158, no. 3 (2003): 229–36. http://dx.doi.org/10.1078/0944-5013-00201.

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27

Gerovac, Benjamin J., and Nevis L. Fregien. "IL-13 Inhibits Multicilin Expression and Ciliogenesis via Janus Kinase/Signal Transducer and Activator of Transcription Independently of Notch Cleavage." American Journal of Respiratory Cell and Molecular Biology 54, no. 4 (April 2016): 554–61. http://dx.doi.org/10.1165/rcmb.2015-0227oc.

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28

Wang, Zhao, Lindsey W. Plasschaert, Shivani Aryal, Nicole A. Renaud, Zinger Yang, Rayman Choo-Wing, Angelica D. Pessotti, et al. "TRRAP is a central regulator of human multiciliated cell formation." Journal of Cell Biology 217, no. 6 (March 27, 2018): 1941–55. http://dx.doi.org/10.1083/jcb.201706106.

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The multiciliated cell (MCC) is an evolutionarily conserved cell type, which in vertebrates functions to promote directional fluid flow across epithelial tissues. In the conducting airway, MCCs are generated by basal stem/progenitor cells and act in concert with secretory cells to perform mucociliary clearance to expel pathogens from the lung. Studies in multiple systems, including Xenopus laevis epidermis, murine trachea, and zebrafish kidney, have uncovered a transcriptional network that regulates multiple steps of multiciliogenesis, ultimately leading to an MCC with hundreds of motile cilia extended from their apical surface, which beat in a coordinated fashion. Here, we used a pool-based short hairpin RNA screening approach and identified TRRAP, an essential component of multiple histone acetyltransferase complexes, as a central regulator of MCC formation. Using a combination of immunofluorescence, signaling pathway modulation, and genomic approaches, we show that (a) TRRAP acts downstream of the Notch2-mediated basal progenitor cell fate decision and upstream of Multicilin to control MCC differentiation; and (b) TRRAP binds to the promoters and regulates the expression of a network of genes involved in MCC differentiation and function, including several genes associated with human ciliopathies.
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Robson, Evie Alexandra, Luke Dixon, Liam Causon, William Dawes, Massimo Benenati, Mahmoud Fassad, Robert Anthony Hirst, et al. "Hydrocephalus and diffuse choroid plexus hyperplasia in primary ciliary dyskinesia-related MCIDAS mutation." Neurology Genetics 6, no. 4 (July 13, 2020): e482. http://dx.doi.org/10.1212/nxg.0000000000000482.

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ObjectiveTo report a neuroradiologic phenotype associated with reduced generation of multiple motile cilia (RGMC) and mutations in the multicilin gene. We hypothesize that the observed phenotype may reflect the emerging role that ependymal cilia play in regulating CSF production.MethodClinical and radiologic records were retrospectively reviewed for 7 consecutive patients diagnosed by the Leicester UK national primary ciliary dyskinesia (PCD) diagnostic laboratory.ResultsOn MRI scanning, all patients demonstrated hydrocephalus, choroid plexus hyperplasia (CPH), and arachnoid cysts. No patient had any sign of neurologic deficit. All patients had significant lung disease.ConclusionsWe conclude that there is a high incidence of hydrocephalus, arachnoid cysts, and CPH in MCIDAS-associated RGMC. In all cases, the observed hydrocephalus seems arrested in childhood without progression or adverse neurologic sequelae. Our new observation of CPH, which is associated with CSF overproduction, is the first macroscopic evidence that ependymal cilia may be involved in the regulation of CSF production and flow. We suggest that brain imaging should be performed in all cases of RGMC and that a diagnosis of PCD or RGMC be strongly considered in patients with unexplained hydrocephalus and a lifelong “wet”-sounding cough.
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Galati, Domenico F., Stephanie Bonney, Zev Kronenberg, Christina Clarissa, Mark Yandell, Nels C. Elde, Maria Jerka-Dziadosz, Thomas H. Giddings, Joseph Frankel, and Chad G. Pearson. "DisAp-dependent striated fiber elongation is required to organize ciliary arrays." Journal of Cell Biology 207, no. 6 (December 22, 2014): 705–15. http://dx.doi.org/10.1083/jcb.201409123.

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Cilia-organizing basal bodies (BBs) are microtubule scaffolds that are visibly asymmetrical because they have attached auxiliary structures, such as striated fibers. In multiciliated cells, BB orientation aligns to ensure coherent ciliary beating, but the mechanisms that maintain BB orientation are unclear. For the first time in Tetrahymena thermophila, we use comparative whole-genome sequencing to identify the mutation in the BB disorientation mutant disA-1. disA-1 abolishes the localization of the novel protein DisAp to T. thermophila striated fibers (kinetodesmal fibers; KFs), which is consistent with DisAp’s similarity to the striated fiber protein SF-assemblin. We demonstrate that DisAp is required for KFs to elongate and to resist BB disorientation in response to ciliary forces. Newly formed BBs move along KFs as they approach their cortical attachment sites. However, because they contain short KFs that are rotated, BBs in disA-1 cells display aberrant spacing and disorientation. Therefore, DisAp is a novel KF component that is essential for force-dependent KF elongation and BB orientation in multiciliary arrays.
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31

Davis, Robert E., R. Jomantiene, Ellen L. Dally, Daniel E. Legard, John L. Maas, and Joseph D. Postman. "POSSIBLE LINK BETWEEN THE RARE PLANT TAXON "FRAGARIA MULTICIPITA" IN CANADA AND A DISEASE PROBLEM IN STRAWBERRY IN FLORIDA." Acta Horticulturae, no. 471 (November 1998): 25–30. http://dx.doi.org/10.17660/actahortic.1998.471.1.

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32

Jomantiene, R., J. L. Maas, E. L. Dally, and R. E. Davis. "021 Strawberry Fruit Phyllody Caused by Phytoplasmas." HortScience 35, no. 3 (June 2000): 391D—391. http://dx.doi.org/10.21273/hortsci.35.3.391d.

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Strawberry fruit phyllody, production of leaves and other vegetative organs from fruit tissue around achenes, has been ascribed to physiological causes due to temperature conditions during transplant cold storage, plant response to changing seasonal conditions at flower initiation time, and to phytoplasma infection. In examination of phylloid fruits from different strawberry clones and from different locations and sources, we found four distinct phytoplasmas associated with phyllody of strawberry fruit: strawberry multicipita (SM) phytoplasma (16S rRNA group VI, subgroup B), STRAWB2 phytoplasma (16S rRNA group I, subgroup K), clover yellow edge phytoplasma (16S rRNA group III, subgroup A), and a new group III phytoplasma. The SM and STRAWB2 phytoplasmas were detected in plants with phylloid fruit that also exhibited stunting and crown proliferation (SM phytoplasma) or stunting and leaf chlorosis (STRAWB2 phytoplasma). In no instances did we fail to detect phytoplasmas in phylloid fruit. To our knowledge, this is the first report to associate strawberry fruit phyllody with the presence of these phytoplasmas and to report that phytoplasmas other than those belonging to 16S rRNA group I (aster yellows group) can also be associated with strawberry fruit phyllody.
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Li, L., K. Picotte, J. Ohli, U. Schuller, and H. Zhao. "PL-02 * NOTCH-MEDIATED SUPPRESSION OF MULTICILIATE DIFFERENTIATION PROMOTES CHOROID PLEXUS TUMOR INITIATION FROM EPITHELIAL PROGENITOR IN RESPONSE TO Shh SIGNALS." Neuro-Oncology 16, suppl 5 (November 1, 2014): v168. http://dx.doi.org/10.1093/neuonc/nou267.2.

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34

Caicci, Federico, Valentina Degasperi, Fabio Gasparini, Giovanna Zaniolo, Marcello Del Favero, Paolo Burighel, and Lucia Manni. "Variability of hair cells in the coronal organ of ascidians (Chordata, Tunicata)." Canadian Journal of Zoology 88, no. 6 (June 2010): 567–78. http://dx.doi.org/10.1139/z10-036.

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The tunicate ascidians are nonvertebrate chordates that possess mechanoreceptor cells in the coronal organ in the oral siphon, which monitor the incoming water flow. Like vertebrate hair cells, the mechanoreceptor–coronal cells are secondary sensory (axonless) cells accompanied by supporting cells and they exhibit morphological diversities of apical specialisations: they are multiciliate in ascidians of the order Enterogona, whereas they are more complex and possess one or two cilia accompanied by stereovilli, also graded in length, in ascidians of the order Pleurogona. In morphology, embryonic origin, and arrangement, coronal sensory cells closely resemble vertebrate hair cells. We describe here the coronal organs of five ascidians ( Pyura haustor (Stimpson, 1864), Pyura stolonifera (Heller, 1878), Styela gibbsii (Stimpson, 1864), Styela montereyensis (Dall, 1872), and Polyandrocarpa zorritensis (Van Name, 1931)), belonging to Pleurogona, also comprising species of one family (Pyuridae), not yet considered, and thus completing our overview of the order. Each species possesses at least two kinds of secondary sensory cells, some of them characterized by stereovilli graded in length. In some species, the coronal sensory cells exhibit secretory activity; in P. haustor, a mitotic sensory cell has also been found. We compare the coronal organ in both ascidians and with other chordate sensory organs formed of secondary sensory cells, and discuss their possible homologies.
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Hiruki, Chuji, and Keri Wang. "Clover proliferation phytoplasma: ‘Candidatus Phytoplasma trifolii’." International Journal of Systematic and Evolutionary Microbiology 54, no. 4 (July 1, 2004): 1349–53. http://dx.doi.org/10.1099/ijs.0.02842-0.

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Clover proliferation phytoplasma (CPR) is designated as the reference strain for the CP phylogenetic group or subclade, on the basis of molecular analyses of genomic DNA, the 16S rRNA gene and the 16S–23S spacer region. Other strains related to CPR include alfalfa witches'-broom (AWB), brinjal little leaf (BLL), beet leafhopper-transmitted virescence (BLTV), Illinois elm yellows (ILEY), potato witches'-broom (PWB), potato yellows (PY), tomato big bud in California (TBBc) and phytoplasmas from Fragaria multicipita (FM). Phylogenetic analysis of the 16S rRNA gene sequences of BLL, CPR, FM and ILEY, together with sequences from 16 other phytoplasmas that belong to the ash yellows (AshY), jujube witches'-broom (JWB) and elm yellows (EY) groups that were available in GenBank, produced a tree on which these phytoplasmas clearly clustered as a discrete group. Three subgroups have been classified on the basis of sequence homology and the collective RFLP patterns of amplified 16S rRNA genes. AWB, BLTV, PWB and TBBc are assigned to taxonomic subgroup CP-A, FM belongs to subgroup CP-B and BLL and ILEY are assigned to subgroup CP-C. Genetic heterogeneity between different isolates of AWB, CPR and PWB has been observed from heteroduplex mobility assay analysis of amplified 16S rRNA genes and the 16S–23S spacer region. Two unique signature sequences that can be utilized to distinguish the CP group from others were present. On the basis of unique properties of the DNA from clover proliferation phytoplasma, the name ‘Candidatus Phytoplasma trifolii’ is proposed for the CP group.
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Singh, Navleen, Tamanna Sarowar, Tasneerm Zahran, and Haotian Zhao. "RARE-14. DISRUPTION OF GEMC1-MCIDAS MULTICILIOGENESIS PROGRAM PROMOTES CHOROID PLEXUS CARCINOMA." Neuro-Oncology 23, Supplement_1 (June 1, 2021): i43. http://dx.doi.org/10.1093/neuonc/noab090.175.

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Abstract Tumors of the choroid plexus (CP) are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP is more benign, CPC is a highly lethal and little understood cancer with poor survival rate and a tendency for recurrence and metastasis. CP tumors are thought to arise from CP epithelial cells that secrets cerebral spinal fluid and generate multiple cilia on their apical surface. Here we show that aberrant NOTCH and Sonic Hedgehog signaling in mice drive tumors that resemble CPC in humans. In contrast to CP epithelial cells with clusters of multiple cilia, NOTCH-driven CP tumors were monociliated, and disruption of the NOTCH complex restored multiciliation and decreased tumor growth. NOTCH suppressed multiciliation in tumor cells by inhibiting the expression of Geminin Coiled-Coil Domain Containing 1 (GEMC1), and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS), early transcriptional regulators of multiciliated cell (MCC) differentiation. Consistently, Gemc1-Mcidas deficiency led to a lack of MCCs in the CP, and impaired the correction of the multiciliation defect in tumor cells by a NOTCH inhibitor. Disturbances to the GEMC1 program are commonly observed in human CPCs characterized by solitary cilia and frequent somatic TP53 mutations. Accordingly, CPC driven by deletion of tumor suppressors Trp53 and Rb1 in mice exhibits a cilia deficit consequent to loss of Gemc1-Mcidas expression. Taken together, these findings reveal that the GEMC1-MCIDAS multiciliogenesis program in the CP is critical for inhibiting tumorigenesis, whereas a defective multiciliation program promotes CPC and may represent a therapeutic avenue for this cancer.
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Zhao, Haotian, Thomas Page, and Tamanna Sarowar. "CSIG-28. REGULATION OF GEMC1 MULTICILIOGENESIS PROGRAM IN CHOROID PLEXUS CARCINOMA." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi39. http://dx.doi.org/10.1093/neuonc/noab196.154.

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Abstract Tumors of the choroid plexus (CP) are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP is more benign, CPC is a highly lethal and little understood cancer with poor survival rate and a tendency for recurrence and metastasis. CP tumors are thought to arise from CP epithelial cells that secrets cerebral spinal fluid and generate multiple cilia on their apical surface. Here we show that aberrant NOTCH and Sonic Hedgehog signaling in mice drive tumors that resemble CPC in humans. In contrast to CP epithelial cells with clusters of multiple cilia, NOTCH-driven CP tumors were monociliated, and disruption of the NOTCH complex restored multiciliation and decreased tumor growth. NOTCH suppressed multiciliation in tumor cells by inhibiting the expression of Geminin Coiled-Coil Domain Containing 1 (GEMC1), and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS), early transcriptional regulators of multiciliated cell (MCC) differentiation. Consistently, Gemc1-Mcidas deficiency led to a lack of MCCs in the CP, and impaired the correction of the multiciliation defect in tumor cells by a NOTCH inhibitor. Disturbances to the GEMC1 program are commonly observed in human CPCs characterized by solitary cilia and frequent somatic TP53 mutations. Accordingly, CPC driven by deletion of tumor suppressors Trp53 and Rb1 in mice exhibits a cilia deficit consequent to loss of Gemc1-Mcidas expression. Taken together, these findings reveal that the GEMC1-MCIDAS multiciliogenesis program in the CP is critical for inhibiting tumorigenesis, whereas a defective multiciliation program promotes CPC and may represent a therapeutic avenue for this cancer.
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Jiao, Jian, Puqi Hu, Ying Li, Chao Cai, Xiangdong Wang, and Luo Zhang. "PM2.5 Upregulates the Expression of MUC5AC via the EGFR-PI3K Pathway in Human Sinonasal Epithelial Cells." International Archives of Allergy and Immunology 183, no. 4 (November 4, 2021): 361–74. http://dx.doi.org/10.1159/000519702.

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<b><i>Background:</i></b> Fine particulate matter (PM) (PM with an aerodynamic diameter &#x3c;2.5 μm, PM2.5) exposure contributes to respiratory disease development and exacerbation. <b><i>Objective:</i></b> We sought to investigate the effect of PM2.5 exposure on mucociliary function in primary human nasal epithelial cells (HNECs) and the underlying mechanism. <b><i>Methods:</i></b> HNECs derived from control subjects and patients with chronic rhinosinusitis with nasal polyps were established as air-liquid interface cultures. Confluent cultures were exposed to 100 or 200 μg/mL PM2.5 for 24 h and assessed for expression of specific mucociliary-associated factors, the percentage of β-tubulin IV-positive and MUC5AC-positive cells, expression of epidermal growth factor receptor (EGFR) ligand and activation of phosphoinositide 3-kinase (PI3K)-AKT/ERK. In addition, cultures pretreated for 30 min with AG1478 (an EGFR inhibitor) or LY294002 (a PI3K inhibitor) following PM2.5 exposure were assessed for MUC5AC mRNA and protein expression. <b><i>Results:</i></b> PM2.5 exposure at 100 or 200 μg/mL for 24 h did not affect geminin coiled-coil domain containing, multiciliate differentiation and DNA synthesis associated cell cycle protein, FOXJ1, or DNAI2 mRNA expression or the percentage of β-tubulin IV-positive cells. However, 200 μg/mL PM2.5 exposure significantly increased mRNA expression of SAM-pointed domain-containing ETS transcription factor and MUC5AC and the percentage of MUC5AC-positive cells. PM2.5 also increased expression of EGFR ligands, including heparin-binding EGF-like growth factor and amphiregulin. Furthermore, PM2.5induced activation of PI3K, AKT, and ERK, and pretreatment of HNECs with AG1478 or LY294002 attenuated PM2.5-induced MUC5AC mRNA and protein expression. <b><i>Conclusions and Clinical Relevance:</i></b> This study demonstrates that short-term PM2.5 exposure increases MUC5AC expression in HNECs. Furthermore, this study shows that PM2.5-induced MUC5AC expression is likely mediated through the EGFR-PI3K pathway.
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39

Rohde, K., and NA Watson. "Sensory Receptors and Epidermal Structures of a Meiofaunal Turbellarian (Proseriata, Monocelididae, Minoninae)." Australian Journal of Zoology 43, no. 1 (1995): 69. http://dx.doi.org/10.1071/zo9950069.

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The senogram (set of sensory receptors) of a proseriate turbellarian from the meiofauna of a high-energy beach in south-eastern Australia is described, based on serial ultrathin sections. It comprises a pair of rhabdomeric eyes that lack a pigment cup, a statocyst located ventro-anteriorly to the brain and consisting of one lithocyte with a single ovoid statolith in the electron-lucent cytoplasm, several parietal and accessory cells and nerve fibres penetrating the statocyst capsule, and at least eight (and possibly eleven) types of epidermal receptors: A, an anterior and antero-lateral receptor with basal bodies and strongly branched processes (modified cilia); B, an 'insunk' collar receptor in all parts of the body surface, with eight microvilli surrounding the single cilium; C, a ciliary bundle arising from basal bodies at the base of a deep pit, in anterior third of body; D, a bundle of dendrites, reaching the surface, in anterior third of body, possibly a protonephridial pore; E, a multiciliate receptor with long branched ciliary rootlets, in anterior and antero-lateral part of body; F, as for E but with a single rootlet; G, as for F but with a vertical and an oblique rootlet arising from the basal body (F and G are possibly modifications of E); H, a receptor with a single cilium and short rootlet, somewhat raised above the epidermal surface; I, a pharyngeal receptor with a short cilium; J, a pharyngeal receptor with a long cilium; K, an anterior receptor with a bulbous cilium. A single cilium or up to three cilia surrounded by a cytoplasmic tube may constitute a further receptor type. Most epidermal perikarya are 'insunk', and epidermal cilia have large anteriorly directed, very thin vertical rootlets and short 'spurs' at the basal body. Bundles of rootlets of epidermal cilia converge towards their tips, some tips located close to the epidermal surface; it is suggested that they may be directly stimulated by mechanical stimuli. The variety of receptors indicates that the animal must respond to a complex array of stimuli. It is stressed that morphological studies of sensory receptors are the basis for an understanding of their function and of the ecological requirements of a species.
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40

Jomantiene, R., J. L. Maas, E. L. Dally, R. E. Davis, and J. D. Postman. "First Report of Clover Proliferation Phytoplasma in Strawberry." Plant Disease 83, no. 10 (October 1999): 967. http://dx.doi.org/10.1094/pdis.1999.83.10.967c.

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In 1996, diseased plants of Fragaria virginiana Duchesne were collected from a native population in Quebec, Canada, and sent to the National Clonal Germplasm Repository in Corvallis, OR, where grafting onto disease-free plants of F. chiloensis (L.) Duchesne (4) was performed. Plants of both species were sent to Beltsville, MD, for identification of a phytoplasma possibly associated with the disease symptoms of dwarfing and multibranching crowns. A phytoplasma was found in both species and characterized as the strawberry “multicipita” (SM) phytoplasma, which is representative of subgroup 16SrVI-B, a new subgroup of the clover proliferation (CP) group (2). In 1999, we observed commercial strawberry (Fragaria × ananassa Duchesne) plants collected in California and Maryland that were stunted and chlorotic or exhibited these symptoms in addition to small, distorted leaves. Infected F. × ananassa plants, as well as diseased F. virginiana and grafted F. chiloensis plants previously infected by the SM phytoplasma, were assessed for phytoplasma infection by nested polymerase chain reactions primed by phytoplasma universal primer pairs R16mF2/R1 and F2n/R2 (1) or P1/P7 (3) and F2n/R2 for amplification of phytoplasma 16S rDNA (16S rRNA gene) sequences. Phytoplasma-characteristic 1.2-kbp DNA sequences were amplified from all diseased plants. No DNA sequences were amplified from healthy plants. Restriction fragment length polymorphism patterns of rDNA digested with AluI, KpnI, HhaI, HaeIII, HinfI, HpaII, MseI, RsaI, and Sau3A1 endonucleases indicated that all plants were infected by a phytoplasma that belonged to subgroup 16SrVI-A (CP phytoplasma subgroup) and that diseased F. virginiana and grafted F. chiloensis plants were infected by both SM and CP. This is the first report of the CP phytoplasma, subgroup 16SrVI-A, infecting strawberry. This report also indicates that the occurrence of the CP phytoplasma in strawberry may be widespread in North America and that F. chiloensis, F. virginiana, and F. × ananassa plants are susceptible to infection by the CP phytoplasma. References: (1) D. E. Gunderson and I.-M. Lee. Phytopathol. Mediterr. 35:144, 1996. (2) R. Jomantiene et al. HortScience 33:1069, 1998. (3) R. Jomantiene et al. Int. J. Syst. Bacteriol. 48:269, 1998. (4) J. D. Postman et al. Acta Hortic. 471:25, 1998.
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Jomantiene, R., J. L. Maas, R. E. Davis, and E. L. Dally. "Molecular Identification and Classification of a Phytoplasma Associated with Phyllody of Strawberry Fruit in Maryland." Plant Disease 85, no. 3 (March 2001): 335. http://dx.doi.org/10.1094/pdis.2001.85.3.335b.

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Several phytoplasmas have been reported to be associated with phyllody of strawberry fruit, including clover yellow edge, clover proliferation, clover phyllody, eastern and western aster yellows, STRAWB2, strawberry multicipita, and Mexican periwinkle virescence phytoplasmas. Plant symptoms in addition to phyllody may include chlorosis, virescence, stunting, or crown proliferation. In this report we describe a new phytoplasma in association with strawberry leafy fruit (SLF) disease in Maryland. Diseased plants exhibited fruit phyllody, floral virescence, leaf chlorosis, and plant stunting. Phytoplasmal 16S rDNA was amplified from SLF diseased plants by using the polymerase chain reaction (PCR) primed by primer pair P1/P7 and was reamplified in nested PCR primed by primer pair R16F2n/R2 (F2n/R2) as previously described (1). These results indicated the presence of a phytoplasma, designated SLF phytoplasma. Identification of SLF phytoplasma was accomplished by restriction fragment length polymorphism (RFLP) analysis of DNA amplified in PCR primed by F2n/R2, using endonuclease enzyme digestion with AluI, HhaI, KpnI, HaeIII, MseI, HpaII, RsaI, and Sau3AI. Phytoplasma classification was done according to the system of Lee et al. (2). RFLP analyses of rDNA amplified in three separate PCRs gave identical patterns. On the basis of collective RFLP patterns of the amplified 16S rDNA, the SLF phytoplasma was classified as a member of group 16SrIII (group III, X-disease phytoplasma group). The HhaI RFLP pattern of SLF 16S rDNA differed from that of the apparently close relative, clover yellow edge (CYE) phytoplasma, and all other phytoplasmas previously described in group III. Based on these results, SLF phytoplasma was classified in a new subgroup, designated subgroup K (III-K), within group III. The 1.2 kbp DNA product of PCR primed by primer pair F2n/R2 was sequenced, and the sequence deposited in GenBank under Accession No. AF 274876. Results from putative restriction site analysis of the sequence were in agreement with the results from actual enzymatic RFLP analysis of rDNA amplified from phylloid strawberry fruit. Although the sequence similarity between the 1.2-kbp fragment from the 16S rDNA of SLF phytoplasma and that of CYE phytoplasma was 99.9%, the Hha1 RFLP pattern of SLF rDNA supports the conclusion that the SLF phytoplasma may be closely related to, but is distinct from, CYE and other strains that are classified in group III. These findings contribute knowledge about the diversity of phytoplasmas affiliated with group III and the diversity of phytoplasmas associated with diseases in strawberry. References: (1) R. Jomantiene et al. Int. J. Syst. Bacteriol. 48:269, 1998. (2) I.-M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998.
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42

Zhao, Huijie, Qingxia Chen, Fan Li, Lihong Cui, Lele Xie, Qiongping Huang, Xin Liang, Jun Zhou, Xiumin Yan, and Xueliang Zhu. "Fibrogranular materials function as organizers to ensure the fidelity of multiciliary assembly." Nature Communications 12, no. 1 (February 24, 2021). http://dx.doi.org/10.1038/s41467-021-21506-8.

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AbstractMulticilia are delicate motile machineries, and how they are accurately assembled is poorly understood. Here, we show that fibrogranular materials (FGMs), large arrays of electron-dense granules specific to multiciliated cells, are essential for their ultrastructural fidelity. Pcm1 forms the granular units that further network into widespread FGMs, which are abundant in spherical FGM cores. FGM cores selectively concentrate multiple important centriole-related proteins as clients, including Cep131 that specifically decorates a foot region of ciliary central pair (CP) microtubules. FGMs also tightly contact deuterosome-procentriole complexes. Disruption of FGMs in mouse cells undergoing multiciliogenesis by Pcm1 RNAi markedly deregulates centriolar targeting of FGM clients, elongates CP-foot, and alters deuterosome size, number, and distribution. Although the multicilia are produced in correct numbers, they display abnormal ultrastructure and motility. Our results suggest that FGMs organize deuterosomes and centriole-related proteins to facilitate the faithful assembly of basal bodies and multiciliary axonemes.
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43

Hao, Kai, Yawen Chen, Xiumin Yan, and Xueliang Zhu. "Cilia locally synthesize proteins to sustain their ultrastructure and functions." Nature Communications 12, no. 1 (November 30, 2021). http://dx.doi.org/10.1038/s41467-021-27298-1.

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AbstractCilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. As cilia are diffusion barrier-gated subcellular compartments, their protein components are thought to come from the cell body through intraflagellar transport or diffusion. Here we show that cilia locally synthesize proteins to maintain their structure and functions. Multicilia of mouse ependymal cells are abundant in ribosomal proteins, translation initiation factors, and RNA, including 18 S rRNA and tubulin mRNA. The cilia actively generate nascent peptides, including those of tubulin. mRNA-binding protein Fmrp localizes in ciliary central lumen and appears to function in mRNA delivery into the cilia. Its depletion by RNAi impairs ciliary local translation and induces multicilia degeneration. Expression of exogenous Fmrp, but not an isoform tethered to mitochondria, rescues the degeneration defects. Therefore, local translation defects in cilia might contribute to the pathology of ciliopathies and other diseases such as Fragile X syndrome.
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Lee, Moonsup, Kunio Nagashima, Jaeho Yoon, Jian Sun, Ziqiu Wang, Christina Carpenter, Hyun-Kyung Lee, Yoo-Seok Hwang, Christopher J. Westlake, and Ira O. Daar. "CEP97 phosphorylation by Dyrk1a is critical for centriole separation during multiciliogenesis." Journal of Cell Biology 221, no. 1 (November 17, 2021). http://dx.doi.org/10.1083/jcb.202102110.

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Proper cilia formation in multiciliated cells (MCCs) is necessary for appropriate embryonic development and homeostasis. Multicilia share many structural characteristics with monocilia and primary cilia, but there are still significant gaps in our understanding of the regulation of multiciliogenesis. Using the Xenopus embryo, we show that CEP97, which is known as a negative regulator of primary cilia formation, interacts with dual specificity tyrosine phosphorylation regulated kinase 1A (Dyrk1a) to modulate multiciliogenesis. We show that Dyrk1a phosphorylates CEP97, which in turn promotes the recruitment of Polo-like kinase 1 (Plk1), which is a critical regulator of MCC maturation that functions to enhance centriole disengagement in cooperation with the enzyme Separase. Knockdown of either CEP97 or Dyrk1a disrupts cilia formation and centriole disengagement in MCCs, but this defect is rescued by overexpression of Separase. Thus, our study reveals that Dyrk1a and CEP97 coordinate with Plk1 to promote Separase function to properly form multicilia in vertebrate MCCs.
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45

Quiroz, Erik J., Seongjae Kim, Lalit K. Gautam, Zea Borok, Christopher Kintner, and Amy L. Ryan. "RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis." Cell Death & Disease 15, no. 1 (January 22, 2024). http://dx.doi.org/10.1038/s41419-024-06440-z.

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AbstractA core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.
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46

Liu, Hao, Jianqun Zheng, Lei Zhu, Lele Xie, Yawen Chen, Yirong Zhang, Wei Zhang, et al. "Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules." Nature Communications 12, no. 1 (October 4, 2021). http://dx.doi.org/10.1038/s41467-021-26058-5.

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AbstractThe axonemal central pair (CP) are non-centrosomal microtubules critical for planar ciliary beat. How they form, however, is poorly understood. Here, we show that mammalian CP formation requires Wdr47, Camsaps, and microtubule-severing activity of Katanin. Katanin severs peripheral microtubules to produce central microtubule seeds in nascent cilia. Camsaps stabilize minus ends of the seeds to facilitate microtubule outgrowth, whereas Wdr47 concentrates Camsaps into the axonemal central lumen to properly position central microtubules. Wdr47 deficiency in mouse multicilia results in complete loss of CP, rotatory beat, and primary ciliary dyskinesia. Overexpression of Camsaps or their microtubule-binding regions induces central microtubules in Wdr47−/− ependymal cells but at the expense of low efficiency, abnormal numbers, and wrong location. Katanin levels and activity also impact the central microtubule number. We propose that Wdr47, Camsaps, and Katanin function together for the generation of non-centrosomal microtubule arrays in polarized subcellular compartments.
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47

Jokura, Kei, Yu Sato, Kogiku Shiba, and Kazuo Inaba. "Two distinct compartments of a ctenophore comb plate provide structural and functional integrity for the motility of giant multicilia." Current Biology, October 2022. http://dx.doi.org/10.1016/j.cub.2022.09.061.

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48

Narita, Keishi, and Sen Takeda. "Ultrastructural evidence for an unusual mode of ciliogenesis in mouse multiciliated epithelia." Microscopy, December 1, 2020. http://dx.doi.org/10.1093/jmicro/dfaa074.

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Abstract Multiciliogenesis is a cascading process for generating hundreds of motile cilia in single cells. In vertebrates, this process has been investigated in the ependyma of brain ventricles and the ciliated epithelia of the airway and oviduct. Although the early steps to amplify centrioles have been characterized in molecular detail, subsequent steps to establish multicilia have been relatively overlooked. Here, we focused on unusual cilia-related structures previously observed in wild-type mouse ependyma using transmission electron microscopy and analyzed their ultrastructural features and the frequency of their occurrence. In the ependyma, $\sim$5% of cilia existed as bundles; while the majority of the bundles were paired, bundles of more than three cilia were also found. Furthermore, apical protrusions harboring multiple sets of axonemes were occasionally observed (0–2 per section), suggesting an unusual mode of ciliogenesis. In trachea and oviduct epithelia, ciliary bundles were absent, but protrusions containing multiple axonemes were observed. At the base of such protrusions, certain axonemes were completely enwrapped by membranes, whereas others remained incompletely enwrapped. These data suggested that the late steps of multiciliogenesis might include a unique process underlying the development of cilia, which is distinct from the ciliogenesis of primary cilia.
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49

Liu, Helu, Huijun Li, Zhihua Jiang, Shibo Jin, Rui Song, Ying Yang, Jun Li, et al. "A local translation program regulates centriole amplification in the airway epithelium." Scientific Reports 13, no. 1 (May 1, 2023). http://dx.doi.org/10.1038/s41598-023-34365-8.

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AbstractBiogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this, Tnrc6a loss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs.
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50

Nikishchenko, Viktoria E., Elena M. Sayenko, and Vyacheslav A. Dyachuk. "First Immunodetection of Sensory and Nervous Systems of Parasitic Larvae (Glochidia) of Freshwater Bivalve Nodularia douglasiae." Frontiers in Physiology 13 (April 11, 2022). http://dx.doi.org/10.3389/fphys.2022.879540.

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Abstract:
Most freshwater mussels have an unusual life cycle that requires host fish species for larval (glochidia) development and dispersal. Glochidia have a unique morphological structure that adapts to parasitic lifestyles and survival. The morphology of the glochidial shells of most Unionoidea, a group of freshwater bivalve mollusks, has been studied in detail using light and scanning electron microscopy. This study summarizes our data on the glochidia shell morphology of the Asian mussel Nodularia douglasiae from two localities in the Primorsky Territory, the Russian Far East. In contrast to the shell morphology of glochidia, little is known about the neurodevelopment of the Unionoidea. Herein, we first demonstrate that the structures of the sensory, muscle, and nervous systems of the glochidia larvae of N. douglasiae differ dramatically from those of the comparable larval systems of marine bivalve species, as revealed through alpha-acetylated tubulin, serotonin (5-HT), and FMRFamide antibodies as well as phalloidin for detection of F-actin and whole-mount confocal microscopy. We found that the glochidia sensory system included four pairs of tubulin-lir multicilia hair cells. Non-ciliar tubulin-lir cells synthesize the neuropeptide FMRFamide and are identified as afferent neurons collecting information from peripheral tubulin-lir hair sensory cells to nervous regulators. The glochidia’s muscular system was represented by a smooth adductor, retractors, and minor muscle bundles associated with the shell and visceral organs. The 5-HT-lir larval system is arranged most simply and consists of two immunopositive neurons innervating the adductor. The FMRFamide-lir system is more complicated and consists of several neuronal centers comprising neuronal bodies and their neurites in different areas of the larva. The FMRFamide-lir neurons are closely associated with sensory hair cells, and others, together with 5-HT-lir neurons, may be involved in the anlagen of adult ganglia. Thus, the nervous system of N. douglasiae glochidia is drastically different from other mollusks and lophotrochozoans because of the absence of an apical organ and the location and composition of FMRFamide and 5-HT cells. Morphological, molecular, and behavioral investigations of Unionoidea taxa need to be further conducted to investigate the parasite-host relationship, nerve-dependent regulation of parasite behavior, and evolution of mollusks.
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