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Bivas Panigrahi, Chang-Hung Lu, Neha Ghayal, Chia-Yuan Chen
The zebrafish sperm activation profoundly depends upon the homogeneous mixing of the sperm cells with its diluent in a quick succession as it alters the cell's extracellular medium and initiates their motility. Manual stirring, the traditional method for zebrafish sperm activation is tedious, time-consuming, and has a poor outcome. In this aspect, an artificial cilia embedded serpentine microfluidic is designed through which hydrodynamic factors of the microfluidic environment can be precisely regulated to harness uniform mixing, hence ensuring a superior sperm activation...
March 15, 2018: Scientific Reports
Morgan L Shannon, Ryann M Fame, Kevin F Chau, Neil Dani, Monica L Calicchio, Gwenaelle S Géléoc, Hart G W Lidov, Sanda Alexandrescu, Maria K Lehtinen
Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous c-Myc is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to anterior choroid plexus and ciliary body. To uncover the consequences of persistent MYC (c-Myc) expression, c-Myc expression was forced in multipotent neural precursors (Nestin-Cre:MYC), which produced a fully penetrant model of choroid plexus carcinoma and ciliary body medulloepithelioma...
March 12, 2018: American Journal of Pathology
Kurt A Zimmerman, Cheng Jack Song, Nancy Gonzalez-Mize, Zhang Li, Bradley K Yoder
Hepatorenal fibrocystic disease (HRFCD) is characterized by cysts in the kidney and liver with associated fibrosis and is the result of defects in proteins required for cilia function or assembly. Previous reports indicate that macrophages, mainly M2-like macrophages, contribute to HRFCD, although the origin (yolk-sac derived resident macrophages vs bone-marrow derived infiltrating macrophages) and contribution of these cells to the observed phenotypes is unknown. Herein, we utilize a congenital model of cilia dysfunction (IFT88Orpk ) to study the importance of macrophages in HRFCD...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Peixuan Xia, Shihua Chu, Geng Liu, Guoqing Chen, Tao Yi, Shi Feng, Hongying Zhou
Kinesin Family Member 3A (KIF3A) was recognized as a key factor of ciliogenesis and transport system of primary cilia in normal cells. However, its possible function on cancer cells has yet to be identified. In the present study, microarray tissue chips, including 230 breast cancer samples, were applied to determine the KIF3A expression pattern by immunological histological chemistry. Statistical analysis on the KIF3A expression level and the currently used clinicopathological characteristics of breast cancer patients was carried out...
April 2018: Biomedical Reports
Dhivya Kumar, Rebecca T Thomason, Maya Yankova, Jonathan D Gitlin, Richard E Mains, Betty A Eipper, Stephen M King
The assembly of membranous extensions such as microvilli and cilia in polarized cells is a tightly regulated, yet poorly understood, process. Peptidylglycine α-amidating monooxygenase (PAM), a membrane enzyme essential for the synthesis of amidated bioactive peptides, was recently identified in motile and non-motile (primary) cilia and has an essential role in ciliogenesis in Chlamydomonas, Schmidtea and mouse. In mammalian cells, changes in PAM levels alter secretion and organization of the actin cytoskeleton...
March 14, 2018: Scientific Reports
Thibaut Eguether, Fabrice P Cordelieres, Gregory J Pazour
The vertebrate hedgehog pathway is organized in primary cilia and hedgehog components relocate into or out of cilia during signaling. Defects in intraflagellar transport (IFT) typically disrupt ciliary assembly and attenuate hedgehog signaling. Determining if IFT drives the movement of hedgehog components is difficult due to the requirement of IFT for building cilia. Unlike most IFT proteins, IFT27 is dispensable for cilia formation but affects hedgehog signaling similar to other IFTs allowing us to examine its role in the dynamics of signaling...
March 14, 2018: Molecular Biology of the Cell
Tomohiro Kubo, Yuqing Hou, Deborah A Cochran, George B Witman, Toshiyuki Oda
Motility of cilia/flagella is generated by a coordinated activity of thousands of dyneins. Inner dynein arms (IDAs) are particularly important for the formation of ciliary/flagellar waveforms, but the molecular mechanism of IDA regulation is poorly understood. Here, we show using cryo-electron tomography and biochemical analyses of Chlamydomonas flagella that a conserved protein FAP44 forms a complex that tethers IDA f (I1 dynein) head domains to the A-tubule of the axonemal outer doublet microtubule. In wild-type flagella, IDA f showed little nucleotide-dependent movement except for a tilt in the f β head perpendicular to the microtubule-sliding direction...
March 14, 2018: Molecular Biology of the Cell
Kirti K Chahal, Milind Parle, Ruben Abagyan
The hedgehog (Hh) pathway plays an important role in cancer development and maintenance, as ~25% of all cancers have aberrant Hh pathway activation. Targeted therapy for inhibition of the Hh pathway was thought to be promising for achieving clinical response in the Hh-dependent cancers. However, the results of new clinical trials with smoothened (SMO) antagonists do not show much success in cancers other than basal cell carcinoma. The studies suggest that the Hh pathway involves multiple mechanisms of activation or inhibition in primary cilia and interactions between several related pathways in different types of cells, which makes this pathway extremely complex...
March 13, 2018: Anti-cancer Drugs
Cilia Mejia-Lancheros, John Mehegan, Celine M Murrin, Cecily C Kelleher
BACKGROUND/OBJECTIVES: The role of smoking from the paternal line during the pre-conception period on grand-child's overweight/obesity and associated underlying pathways are uncertain. We examined whether the smoking status from the paternal line was associated with the grand-child's higher weight at birth, and overweight or obesity at 5 and 9 years of age. The grandparental smoking effect from the maternal line was also explored. SUBJECTS/METHODS: Participants were fathers and grandparents and grand-children from the Lifeways Cross Generational Cohort (N = 1021 for the analysis at birth; N = 562 and N = 284 for the analysis at 5 and 9 years, respectively)...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Stephen M King, Winfield S Sale
Motility of cilia (also known as flagella in some eukaryotes) is based on axonemal doublet microtubule sliding that is driven by the dynein molecular motors. Dyneins are organized into intricately patterned inner and outer rows of arms, whose collective activity is to produce inter-microtubule movement. However, to generate a ciliary bend, not all dyneins can be active simultaneously. The switch point model accounts, in part, for how dynein motors are regulated during ciliary movement. On the basis of this model, supported by key direct experimental observations as well as more recent theoretical and structural studies, we are now poised to understand the mechanics of how ciliary dynein coordination controls axonemal bend formation and propagation...
March 15, 2018: Molecular Biology of the Cell
Christina Gerth-Kahlert, Samuel Koller
Ciliopathies are disorders caused by ciliary dysfunction and can affect an organ system or tissues. Isolated or syndromic retinal dystrophies are the most common ocular manifestation of ciliopathies. The photoreceptor connecting cilium plays a leading role in these ciliopathy-related retinal dystrophies. Dysfunctional photoreceptor cilia cause the most severe type of retinal dystrophy: Leber's congenital amaurosis (LCA). The most common syndromic ciliopathies with an ocular manifestation are Bardet-Biedl syndrome (BBS) and Usher syndrome...
March 2018: Klinische Monatsblätter Für Augenheilkunde
Kelsey H Elliott, Grethel Millington, Samantha A Brugmann
BACKGROUND: Submandibular glands (SMGs) are specialized epithelial structures which generate saliva necessary for mastication and digestion. Loss of SMGs can lead to inflammation, oral lesions, fungal infections, problems with chewing/swallowing, and tooth decay. Understanding the development of the SMG is important for developing therapeutic options for patients with impaired SMG function. Recent studies have suggested Sonic hedgehog (Shh) signaling in the epithelium plays an integral role in SMG development; however, the mechanism by which Shh influences gland development remains nebulous...
March 13, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Takuya Ohmura, Yukinori Nishigami, Atsushi Taniguchi, Shigenori Nonaka, Junichi Manabe, Takuji Ishikawa, Masatoshi Ichikawa
An important habit of ciliates, namely, their behavioral preference for walls, is revealed through experiments and hydrodynamic simulations. A simple mechanical response of individual ciliary beating (i.e., the beating is stalled by the cilium contacting a wall) can solely determine the sliding motion of the ciliate along the wall and result in a wall-preferring behavior. Considering ciliate ethology, this mechanosensing system is likely an advantage in the single cell's ability to locate nutrition. In other words, ciliates can skillfully use both the sliding motion to feed on a surface and the traveling motion in bulk water to locate new surfaces according to the single "swimming" mission...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Marjan M Hashemi, Brett S Holden, Maddison F Taylor, John Wilson, Jordan Coburn, Brian Hilton, Tania Nance, Shawn Gubler, Carl Genberg, Shenglou Deng, Paul B Savage
Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. A characteristic of an optimal therapeutic for use in the lungs and trachea is the exertion of potent antimicrobial activities without damaging the cilia that play a critical role in these tissues...
March 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nicky O'Boyle, Erin Sutherland, Catherine C Berry, Robert L Davies
Respiratory tract infections are of significant concern in the agriculture industry. There is a requirement for the development of well-characterised in vitro epithelial cell culture models in order to dissect the diverse molecular interactions occurring at the host-pathogen interface in airway epithelia. We have analysed key factors that influence growth and differentiation of ovine tracheal epithelial cells in an air-liquid interface (ALI) culture system. Cellular differentiation was assessed at 21 days post-ALI, a time-point which we have previously shown to be sufficient for differentiation in standard growth conditions...
2018: PloS One
Gang Fu, Qian Wang, Nhan Phan, Paulina Urbanska, Ewa Joachimiak, Jianfeng Lin, Dorota Wloga, Daniela Nicastro
Motile cilia are essential for propelling cells and moving fluids across tissues. The activity of axonemal dynein motors must be precisely coordinated to generate ciliary motility, but their regulatory mechanisms are not well understood. The tether and tether head (T/TH) complex was hypothesized to provide mechanical feedback during ciliary beating because it links the motor domains of the regulatory I1 dynein to the ciliary doublet microtubule. Combining genetic and biochemical approaches with cryo-electron tomography, we identified FAP44 and FAP43 (plus the algae-specific, FAP43-redundant FAP244) as T/TH components...
March 7, 2018: Molecular Biology of the Cell
Sun K Kim, Siwei Zhang, Michael E Werner, Eva J Brotslaw, Jennifer W Mitchell, Mohamed M Altabbaa, Brian J Mitchell
Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division...
March 7, 2018: Journal of Cell Biology
Yi Xu, Ho Jung Ju, S DeBlasio, Elizabeth J Carino, R Johnson, M MacCoss, M Cilia Heck, W Allen Miller, S M Gray
Translational readthrough of the stop codon of the capsid protein (CP) open reading frame (ORF) is used by members of the Luteoviridae to produce their minor capsid protein as a readthrough protein (RTP). The elements regulating RTP expression are not well understood, but involve long-distance interactions between RNA domains. Using high-resolution mass spectrometry, glutamine and tyrosine were identified as the primary amino acids inserted at the stop codon of Potato leafroll virus (PLRV) CP ORF. We characterized the contributions of a cytidine-rich domain immediately downstream, and a branched stem-loop structure 600-700 nucleotides downstream of the CP stop codon...
March 7, 2018: Journal of Virology
Dorian Farache, Laurent Emorine, Laurence Haren, Andreas Merdes
Microtubules are major constituents of the cytoskeleton in all eukaryotic cells. They are essential for chromosome segregation during cell division, for directional intracellular transport and for building specialized cellular structures such as cilia or flagella. Their assembly has to be controlled spatially and temporally. For this, the cell uses multiprotein complexes containing γ-tubulin. γ-Tubulin has been found in two different types of complexes, γ-tubulin small complexes and γ-tubulin ring complexes...
March 2018: Open Biology
Huawen Lin, Zhengyan Zhang, Carlo Iomini, Susan K Dutcher
Intraflagellar transport moves proteins in and out of flagella/cilia and it is essential for the assembly of these organelles. Using whole-genome sequencing, we identified splice site mutations in two IFT genes, IFT81 ( fla9 ) and IFT121 ( ift121-2 ), which lead to flagellar assembly defects in the unicellular green alga Chlamydomonas reinhardtii The splicing defects in these ift mutants are partially corrected by mutations in two conserved spliceosome proteins, DGR14 and FRA10. We identified a dgr14 deletion mutant, which suppresses the 3' splice site mutation in IFT81 , and a frameshift mutant of FRA10 , which suppresses the 5' splice site mutation in IFT121 Surprisingly, we found dgr14-1 and fra10 mutations suppress both splice site mutations...
March 2018: Open Biology
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