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https://www.readbyqxmd.com/read/28528628/millisecond-time-resolution-correlative-light-and-electron-microscopy-for-dynamic-cellular-processes
#1
Ludek Stepanek, Gaia Pigino
Molecular motors propel cellular components at velocities up to microns per second with nanometer precision. Imaging techniques combining high temporal and spatial resolution are therefore indispensable to understand the cellular mechanics at the molecular level. For example, intraflagellar transport (IFT) trains constantly shuttle ciliary components between the base and tip of the eukaryotic cilium. 3-D electron microscopy has revealed IFT train morphology and position, but was unable to correlate these features with the direction of train movement...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28524820/chemical-structure-guided-design-of-dynapyrazoles-potent-cell-permeable-dynein-inhibitors-with-a-unique-mode-of-action
#2
Jonathan Baruch Steinman, Cristina C Santarossa, Rand M Miller, Lola S Yu, Anna S Serpinskaya, Hideki Furukawa, Sachie Morimoto, Yuta Tanaka, Mitsuyoshi Nishitani, Moriteru Asano, Ruta Zalyte, Alison E Ondrus, Alex G Johnson, Fan Ye, Maxence V Nachury, Yoshiyuki Fukase, Kazuyoshi Aso, Michael A Foley, Vladimir I Gelfand, James K Chen, Andrew P Carter, Tarun M Kapoor
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that power transport of cellular cargos towards microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally-constrained isosteres...
May 19, 2017: ELife
https://www.readbyqxmd.com/read/28513607/variants-in-ttc25-affect-autistic-trait-in-patients-with-autism-spectrum-disorder-and-general-population
#3
Dina Vojinovic, Nathalie Brison, Shahzad Ahmad, Ilse Noens, Irene Pappa, Lennart C Karssen, Henning Tiemeier, Cornelia M van Duijn, Hilde Peeters, Najaf Amin
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study...
May 17, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28513435/a-bioactive-peptide-amidating-enzyme-is-required-for-ciliogenesis
#4
Dhivya Kumar, Daniela Strenkert, Ramila S Patel-King, Michael T Leonard, Sabeeha S Merchant, Richard E Mains, Stephen M King, Betty A Eipper
The pathways controlling cilium biogenesis in different cell types have not been fully elucidated. We recently identified peptidylglycine α-amidating monooxygenase (PAM), an enzyme required for generating amidated bioactive signaling peptides, in Chlamydomonas and mammalian cilia. Here, we show that PAM is required for the normal assembly of motile and primary cilia in Chlamydomonas, planaria and mice. Chlamydomonas PAM knockdown lines failed to assemble cilia beyond the transition zone, had abnormal Golgi architecture and altered levels of cilia assembly components...
May 17, 2017: ELife
https://www.readbyqxmd.com/read/28500222/energy-requirements-of-odor-transduction-in-the-chemosensory-cilia-of-olfactory-sensory-neurons-rely-on-oxidative-phosphorylation-and-glycolytic-processing-of-extracellular-glucose
#5
Pablo S Villar, Ricardo Delgado, Cecilia Vergara, Juan G Reyes, Juan Bacigalupo
The mechanisms that power the physiological events occuring in cilia, flagella and microvilli are of fundamental importance for the functions of these important and ubicuous organelles. The olfactory epithelium (OE) is mostly populated by ciliated olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with apical microvilli. The only OSN dendrite extends to the surface forming a knob projecting several chemosensory cilia of approximately 50 x 0.2 μm, devoid of inner membranes embedded in a mucus layer...
May 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28495528/hepatic-ischemia-reperfusion-injury-disrupts-the-homeostasis-of-kidney-primary-cilia-via-oxidative-stress
#6
Sang Jun Han, Hee-Seong Jang, Sung Young Seu, Hee-Jung Cho, Yoon Jin Hwang, Jee In Kim, Kwon Moo Park
Acute kidney injury (AKI) is a major complication of hepatic surgeries. The primary cilium protrudes to the lumen of kidney tubules and plays an important role in renal functions. Disruption of primary cilia homeostasis is highly associated with human diseases including AKI. Here, we investigated whether transient hepatic ischemia induces length change and deciliation of kidney primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress regulates those. HIR induced damages to the liver and kidney with increases in ROS/oxidative stress...
May 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28487963/polymer-brushes-and-their-possible-applications-in-artificial-cilia-research-review
#7
Jian Zhu, Xuemei Jiang, Jun Zhong, Yiyuan Duan
The review aimed to assess the current research status of polymer brushes and artificial cilia, based on the analysis of polymer brush properties and the structure and function of natural cilia. The application of polymer brushes to develop artificial cilia has attracted increasing research interest, with rheological analysis often employed as an entry point for polymer mechanics. The present review assessed whether combing polymer brushes with artificial cilia, along with appropriate designing of high‑polymer materials and use of suitable equipment, may to the development of a polymer net‑structured material to imitate the morphology and functionality of a natural cilium system...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28479320/dynein-driven-retrograde-intraflagellar-transport-is-triphasic-in-c-%C3%A2-elegans-sensory-cilia
#8
Peishan Yi, Wen-Jun Li, Meng-Qiu Dong, Guangshuo Ou
Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance. Inactivation of dynein-2 by mutations in DYNC2H1 causes skeletal dysplasias, and it remains unclear how the dynein-2 heavy chain moves in cilia. Here, using the genome-editing technique to produce fluorescent dynein-2 heavy chain in Caenorhabditis elegans, we show by high-resolution live microscopy that dynein-2 moves in a surprising way along distinct ciliary domains. Dynein-2 shows triphasic movement in the retrograde direction: dynein-2 accelerates in the ciliary distal region and then moves at maximum velocity and finally decelerates adjacent to the base, which may represent a physical obstacle due to transition zone barriers...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28477148/a-low-ca-2-i-induced-enhancement-of-camp-activated-ciliary-beating-by-pde1a-inhibition-in-mouse-airway-cilia
#9
Haruka Kogiso, Shigekuni Hosogi, Yukiko Ikeuchi, Saori Tanaka, Chikao Shimamoto, Hitoshi Matsumura, Takashi Nakano, Koh-Ichi Sano, Toshio Inui, Yoshinori Marunaka, Takashi Nakahari
This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β2-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course...
May 5, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28472849/evidence-for-a-self-organized-compliant-mechanism-for-the-spontaneous-steady-beating-of-cilia
#10
Kenneth W Foster, Jyothish Vidyadharan, Ashok S Sangani
Cilia or eukaryotic flagella are slender 200-nm-diameter organelles that move the immersing fluid relative to a cell and sense the environment. Their core structure is nine doublet microtubules (DMTs) arranged around a central-pair. When motile, thousands of tiny motors slide the DMTs relative to each other to facilitate traveling waves of bending along the cilium's length. These motors provide the energy to change the shape of the cilium and overcome the viscous forces of moving in the surrounding fluid. In planar beating, motors walk toward where the cilium is attached to the cell body...
May 4, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28468945/primary-cilia-control-the-maturation-of-tubular-lumen-in-renal-collecting-duct-epithelium
#11
Thomas Ernandez, Olga Komarynets, Alexandra Chassot, Soushma Sougoumarin, Priscilla Soulie, Yubao Wang, Roberto Montesano, Eric Feraille
The key role of the primary cilium in developmental processes is illustrated by ciliopathies resulting from genetic defects of its components. Ciliopathies include a large variety of dysmorphic syndromes that share in common the presence of multiple kidney cysts. These observations suggest that primary cilia may control morphogenetic processes in the developing kidney. In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen/matrigel matrix...
May 3, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28460050/ift81-as-a-candidate-gene-for-nonsyndromic-retinal-degeneration
#12
Rachayata Dharmat, Wei Liu, Zhongqi Ge, Zixi Sun, Lizhu Yang, Yumei Li, Keqing Wang, Kandace Thomas, Ruifang Sui, Rui Chen
Purpose: IFT81, a core component of the IFT-B complex, involved in the bidirectional transport of ciliary proteins, has been recently implicated in syndromic ciliopathies. However, none of the IFT-B core complex proteins have been associated with nonsyndromic retinal dystrophies. Given the importance of ciliary transport in photoreceptor function and structural maintenance, we sought to investigate the impact of IFT (intraflagellar transport) mutations in nonsyndromic retinopathies. Methods: Whole exome sequencing was performed on 50 cone-rod dystrophy (CRD) patients that were previously screened for mutations in known retinal disease genes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28456657/topography-of-calcium-phosphate-ceramics-regulates-primary-cilia-length-and-tgf-receptor-recruitment-associated-with-osteogenesis
#13
Jingwei Zhang, Melis Dalbay, Xiaoman Luo, Erik Vrij, Davide Barbieri, Lorenzo Moroni, Joost D de Bruijn, Clemens A van Blitterswijk, Paul Chapple, Martin M Knight, Huipin Yuan
The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signaling also initiates osteogenic differentiation. TGFβ signaling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry...
April 26, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28453661/photoreceptor-outer-segment-as-a-sink-for-membrane-proteins-hypothesis-and-implications-in-retinal-ciliopathies
#14
Seongjin Seo, Poppy Datta
The photoreceptor outer segment (OS) is a unique modification of the primary cilium, specialized for light perception. Being homologous organelles, the primary cilium and the OS share common building blocks and molecular machinery to construct and maintain them. The OS, however, has several unique structural features that are not seen in primary cilia. Although these unique features of the OS have been well documented, their implications in protein localization have been under-appreciated. In this review, we compare the structural properties of the primary cilium and the OS, and propose a hypothesis that the OS can act as a sink for membrane proteins...
April 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448009/using-primary-neurosphere-cultures-to-study-primary-cilia
#15
Issei S Shimada, Hemant Badgandi, Bandarigoda N Somatilaka, Saikat Mukhopadhyay
The primary cilium is fundamentally important for the proliferation of neural stem/progenitor cells and for neuronal differentiation during embryonic, postnatal, and adult life. In addition, most differentiated neurons possess primary cilia that house signaling receptors, such as G-protein-coupled receptors, and signaling molecules, such as adenylyl cyclases. The primary cilium determines the activity of multiple developmental pathways, including the sonic hedgehog pathway during embryonic neuronal development, and also functions in promoting compartmentalized subcellular signaling during adult neuronal function...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#16
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444394/tissue-specific-dissociation-of-diurnal-transcriptome-rhythms-during-sleep-restriction-in-mice
#17
Jana Husse, Jana-Thabea Kiehn, Johanna L Barclay, Nadine Naujokat, Judit Meyer-Kovac, Hendrik Lehnert, Henrik Oster
Study objectives: Shortened or mistimed sleep affects metabolic homeostasis, which may in part be mediated by dysregulation of endogenous circadian clocks. In this study, we assessed the contribution of sleep disruption to metabolic dysregulation by analysing diurnal transcriptome regulation in metabolic tissues of mice subjected to a sleep restriction paradigm. Methods: Male mice were subjected to 2x5 days of sleep restriction (SR) with enforced waking during the first six hours of the light phase...
April 24, 2017: Sleep
https://www.readbyqxmd.com/read/28442542/missense-mutations-in-the-wd40-domain-of-ahi1-cause-non-syndromic-retinitis-pigmentosa
#18
Thanh-Minh T Nguyen, Sarah Hull, Ronald Roepman, L Ingeborgh van den Born, Machteld M Oud, Erik de Vrieze, Lisette Hetterschijt, Stef J F Letteboer, Sylvia E C van Beersum, Ellen A Blokland, Helger G Yntema, Frans P M Cremers, Paul A van der Zwaag, Gavin Arno, Erwin van Wijk, Andrew R Webster, Lonneke Haer-Wigman
BACKGROUND: Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). METHODS: Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling...
April 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28441853/-differentially-expressed-genes-analysis-in-expression-profile-data-of-pulmonary-fibrosis-with-pulmonary-hypertension
#19
R Miao, D Leng, Y Wang, J F Li, J N Gong, Y Liang, Y H Yang
Objective: To analyze the differential gene expression of patients with idiopathic pulmonary fibrosis and pulmonary hypertension (IPF-PH). Methods: The expression profile data of GSE15197 was downloaded from the Gene Expression Omnibus (GEO) database. Bonferroni algorithm was used to identify the differentially expressed genes of pulmonary tissues from IPF-PH, idiopathic pulmonary arterial hypertension (IPAH) and Normal groups. Principal component analysis was used to extract the principal components of three types of samples and differentially expressed genes were obtained...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28432921/gates-for-soluble-and-membrane-proteins-and-two-trafficking-systems-ift-and-lift-establish-a-dynamic-ciliary-signaling-compartment
#20
REVIEW
Victor L Jensen, Michel R Leroux
Primary cilia are microtubule-based organelles found on most mammalian cell surfaces. They possess a soluble matrix and membrane contiguous with the cell body cytosol and plasma membrane, and yet, have distinct compositions that can be modulated to enable dynamic signal transduction. Here, we discuss how specialized ciliary compartments are established using a coordinated network of gating, trafficking and targeting activities. Cilium homeostasis is maintained by a size-selective molecular mesh that limits soluble protein entry, and by a membrane diffusion barrier localized at the transition zone...
April 19, 2017: Current Opinion in Cell Biology
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