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https://www.readbyqxmd.com/read/29789632/the-developmental-process-of-the-growing-motile-ciliary-tip-region
#1
Matthew J Reynolds, Tanaporn Phetruen, Rebecca L Fisher, Ke Chen, Brian T Pentecost, George Gomez, Puey Ounjai, Haixin Sui
Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29781741/slowly-progressive-retinitis-pigmentosa-caused-by-two-novel-mutations-in-the-mak-gene
#2
Joanna Monika Gray, Harry Otway Orlans, Morag Shanks, Penny Clouston, Robert Elvis MacLaren
BACKGROUND: The growing number of clinical trials currently underway for inherited retinal diseases has highlighted the importance of achieving a molecular diagnosis for all new cases presenting to hospital eye services. The male germ cell-associated kinase (MAK) gene encodes a cilium-associated protein selectively expressed in the retina and testis, and has recently been implicated in autosomal recessive retinitis pigmentosa (RP). Whole exome sequencing has previously identified a homozygous Alu insertion in probands with recessive RP and nonsense and missense mutations have also been reported...
May 21, 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/29779043/glis1-3-transcription-factors-critical-roles-in-the-regulation-of-multiple-physiological-processes-and-diseases
#3
REVIEW
Anton M Jetten
Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29745101/simulations-of-centriole-of-polarized-centrosome-as-a-monopole-antenna-in-immune-and-viral-synapses
#4
Josef Dvorak, Bohuslav Melichar, Alzbeta Filipova, Jana Grimova, Nela Grimova, Aneta Rozsypalova, David Buka, Rene Voboril, Radek Zapletal, Tomas Buchler, Igor Richter, David Buka
The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29742020/actin-dependent-regulation-of-cilia-length-by-the-inverted-formin-fhdc1
#5
Sarah J Copeland, Andrea McRae, Giulia Guarguaglini, Laura Trinkle-Mulcahy, John W Copeland
A primary cilium is found on most mammalian cells where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis reflecting the ubiquity of their function and the number of proteins required for cilia assembly. Proper cilia length is necessary for cilia signaling and is regulated through a poorly understood balance of assembly and disassembly rates. FHDC1 is a unique member of the formin family of cytoskeletal regulatory proteins...
May 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29737998/metachronal-motion-of-artificial-magnetic-cilia
#6
Srinivas Hanasoge, Peter J Hesketh, Alexander Alexeev
Organisms use hair-like cilia that beat in a metachronal fashion to actively transport fluid and suspended particles. Metachronal motion emerges due to a phase difference between beating cycles of neighboring cilia and appears as traveling waves propagating along ciliary carpet. In this work, we demonstrate biomimetic artificial cilia capable of metachronal motion. The cilia are micromachined magnetic thin filaments attached at one end to a substrate and actuated by a uniform rotating magnetic field. We show that the difference in magnetic cilium length controls the phase of the beating motion...
May 8, 2018: Soft Matter
https://www.readbyqxmd.com/read/29737248/targeted-therapies-for-autosomal-dominant-polycystic-kidney-disease
#7
Cherie Stayner, Darby G Brooke, Michael Bates, Michael R Eccles
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell...
May 7, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29731308/nup98-sets-the-size-exclusion-diffusion-limit-through-the-ciliary-base
#8
S Joseph Endicott, Martina Brueckner
The primary cilium maintains a well-regulated complement of soluble and membrane proteins, allowing it to mediate a variety of signaling pathways that are essential for development and tissue homeostasis [1-3]. Entry into the cilium is regulated at the base, where a complex containing nucleoporins, referred to as the "ciliary pore complex" (CPC), has been proposed to set a size-exclusion limit for soluble molecule diffusion into the cilium [4-6]. Here, using a fluorescence-based diffusion trap system, we demonstrate that NUP98, a component of the phenylalanine-glycine (FG) hydrogel permeability barrier at the nuclear pore complex [7, 8], limits the diffusion of soluble molecules >70 kDa into the cilium in cultured mammalian cells...
April 26, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29727300/rab23-and-developmental-disorders
#9
Catherine H H Hor, Bor Luen Tang, Eyleen L K Goh
Rab23 is a conserved member of the Rab family of small GTPases that regulates membrane trafficking in eukaryotes. It is unique amongst the Rabs in terms of its implicated role in mammalian development, as originally illustrated by the embryonic lethality and open neural tube phenotype of a spontaneous mouse mutant that carries homozygous mutation of open brain, a gene encoding Rab23. Rab23 was initially identified to act as an antagonist of Sonic hedgehog (Shh) signaling, and has since been implicated in a number of physiological and pathological roles, including oncogenesis...
May 4, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29723155/a-pilot-study-exploring-the-impact-of-cardiac-medications-on-ciliary-beat-frequency-possible-implications-for-clinical-management
#10
Rohit S Loomba, Abhinav Bhushan, Adeleye J Afolayan
BACKGROUND: Cilia are involved in several physiologic processes, and at least a single primary cilium can be found on nearly every cell in the human body. Various factors, such as pH, temperature, exposure to medications and toxins can impact ciliary function as is manifested by changes in the ciliary beat frequency. Those with ciliary dyskinesia may also have congenital cardiac malformations and may require care in a cardiac intensive care unit. This study investigates the effect on the ciliary beat frequency of medications frequently used in a cardiac intensive care unit...
May 3, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29718757/arl2bp-a-protein-linked-to-retinitis-pigmentosa-is-needed-for-normal-photoreceptor-cilia-doublets-and-outer-segment-structure
#11
Abigail R Moye, Ratnesh Singh, Victoria A Kimler, Tanya L Dilan, Daniella Munezero, Thamaraiselvi Saravanan, Andrew F X Goldberg, Visvanathan Ramamurthy
The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous discs that contain the proteins needed for phototransduction and vision. Though cilia formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins which often result in malformed outer segments and lead to blinding diseases. To investigate how ciliary proteins contribute to outer segment formation, we generated a knockout mouse model for ARL2BP, a ciliary protein linked to Retinitis Pigmentosa...
May 2, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29713460/sensing-the-cilium-digital-capture-of-ciliary-data-for-comparative-genomics-investigations
#12
Karen R Christie, Judith A Blake
Background: Cilia are specialized, hair-like structures that project from the cell bodies of eukaryotic cells. With increased understanding of the distribution and functions of various types of cilia, interest in these organelles is accelerating. To effectively use this great expansion in knowledge, this information must be made digitally accessible and available for large-scale analytical and computational investigation. Capture and integration of knowledge about cilia into existing knowledge bases, thus providing the ability to improve comparative genomic data analysis, is the objective of this work...
2018: Cilia
https://www.readbyqxmd.com/read/29706353/patient-ipsc-derived-kidney-organoids-show-functional-validation-of-a-ciliopathic-renal-phenotype-and-reveal-underlying-pathogenetic-mechanisms
#13
Thomas A Forbes, Sara E Howden, Kynan Lawlor, Belinda Phipson, Jovana Maksimovic, Lorna Hale, Sean Wilson, Catherine Quinlan, Gladys Ho, Katherine Holman, Bruce Bennetts, Joanna Crawford, Peter Trnka, Alicia Oshlack, Chirag Patel, Andrew Mallett, Cas Simons, Melissa H Little
Despite the increasing diagnostic rate of genomic sequencing, the genetic basis of more than 50% of heritable kidney disease remains unresolved. Kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of individuals affected by inherited renal disease represent a potential, but unvalidated, platform for the functional validation of novel gene variants and investigation of underlying pathogenetic mechanisms. In this study, trio whole-exome sequencing of a prospectively identified nephronophthisis (NPHP) proband and her parents identified compound-heterozygous variants in IFT140, a gene previously associated with NPHP-related ciliopathies...
April 21, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29702220/dicam-promotes-proliferation-and-maturation-of-chondrocyte-through-indian-hedgehog-signaling-in-primary-cilia
#14
S Han, H-R Park, E-J Lee, J-A Jang, M-S Han, G-W Kim, J-H Jeong, J-Y Choi, F Beier, Y-K Jung
OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15...
April 25, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29689227/how-the-ciliary-membrane-is-organized-inside-out-to-communicate-outside-in
#15
REVIEW
Galo Garcia, David R Raleigh, Jeremy F Reiter
Cilia, organelles that move to execute functions like fertilization and signal to execute functions like photoreception and embryonic patterning, are composed of a core of nine-fold doublet microtubules overlain by a membrane. Distinct types of cilia display distinct membrane morphologies, ranging from simple domed cylinders to the highly ornate invaginations and membrane disks of photoreceptor outer segments. Critical for the ability of cilia to signal, both the protein and the lipid compositions of ciliary membranes are different from those of other cellular membranes...
April 23, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29687140/ciliary-proteins-fap43-and-fap44-interact-with-each-other-and-are-essential-for-proper-cilia-and-flagella-beating
#16
Paulina Urbanska, Ewa Joachimiak, Rafał Bazan, Gang Fu, Martyna Poprzeczko, Hanna Fabczak, Daniela Nicastro, Dorota Wloga
Cilia beating is powered by the inner and outer dynein arms (IDAs and ODAs). These multi-subunit macrocomplexes are arranged in two rows on each outer doublet along the entire cilium length, except its distal end. To generate cilia beating, the activity of ODAs and IDAs must be strictly regulated locally by interactions with the dynein arm-associated structures within each ciliary unit and coordinated globally in time and space between doublets and along the axoneme. Here, we provide evidence of a novel ciliary complex composed of two conserved WD-repeat proteins, Fap43p and Fap44p...
April 23, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29678909/restoration-of-physiological-expression-of-5-ht6-into-the-primary-cilia-of-null-mutant-neurons-lengthens-both-primary-cilia-and-dendrites
#17
Atom J Lesiak, Matthew Brodsky, Nathalie Cohenca, Alexandra G Croicu, John F Neumaier
5-HT6 serotonin receptors are promising targets for a variety of neuropsychiatric disorders and have been linked to several cellular signaling cascades. Endogenous 5-HT6 receptors are restricted to the primary neuronal cilium, a small sensory organelle stemming from the cell body that receives numerous extra-synaptic signals. Inhibition of 5-HT6 receptors decreases cilia length in primary neuronal cultures, but the signaling mechanisms involved are still unclear. Intense overexpression of exogenous 5-HT6 receptors increases the likelihood for receptors to localize outside of the primary cilium and have been associated with changes in cilia morphology and dendritic outgrowth...
April 20, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29674126/bbs9-gene-in-nonsyndromic-craniosynostosis-role-of-the-primary-cilium-in-the-aberrant-ossification-of-the-suture-osteogenic-niche
#18
Marta Barba, Lorena Di Pietro, Luca Massimi, Maria Concetta Geloso, Paolo Frassanito, Massimo Caldarelli, Fabrizio Michetti, Stefano Della Longa, Paul A Romitti, Concezio Di Rocco, Alessandro Arcovito, Ornella Parolini, Gianpiero Tamburrini, Camilla Bernardini, Simeon Antonov Boyadjiev, Wanda Lattanzi
Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly...
April 16, 2018: Bone
https://www.readbyqxmd.com/read/29669747/the-role-of-the-microglial-cx3cr1-pathway-in-the-post-natal-maturation-of-retinal-photoreceptors
#19
Andrew I Jobling, Michelle Waugh, Kirstan A Vessey, Joanna A Phipps, Lidia Trogrlic, Una Greferath, Samuel A Mills, Zhi L Tan, Michelle M Ward, Erica L Fletcher
Microglia are the resident immune cells of the CNS and their response to infection, injury and disease is well documented. More recently, microglia have been shown to play a role in normal CNS development, with the fractalkine-Cx3cr1 signalling pathway of particular importance. This work describes the interaction between the light sensitive photoreceptors and microglia during eye opening, a time of post-natal photoreceptor maturation. Genetic removal of Cx3cr1 ( Cx3cr1GFP/GFP ), led to an early retinal dysfunction soon after eye opening (P17) and cone photoreceptor loss (P30 onwards) in mice of either sex...
April 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29658664/-primary-cilium-acts-as-an-oxygen-sensor-in-pc12-cells
#20
Yuhai Gao, Xinzhu Qi, Jian Zhou, Xin Wang, Keming Chen, Huiping Ma
<b>Objective:</b> To investigate the function of primary cilium as an oxygen sensor in PC12 cells. <b>Methods:</b> The PC12 cells were transfected with IFT88 siRNA. The nuclear translocation of hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were observed by immunofluorescence staining; and the mRNA expressions of <i>HIF-1α, Nrf2</i>, vascular endothelial growth factor (<i>VEGF</i>) and superoxide dismutase (<i>SOD</i>) were detected by real-time RT-PCR...
May 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
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