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https://www.readbyqxmd.com/read/29777959/extracellular-matrix-expression-in-human-pluripotent-stem-cell-derived-retinal-organoids-recapitulates-retinogenesis-in-vivo-and-reveals-an-important-role-for-impg1-and-cd44-in-the-development-of-photoreceptors-and-interphotoreceptor-matrix
#1
Majed Felemban, Birthe Dorgau, Nicola Claire Hunt, Dean Hallam, Darin Zerti, Roman Bauer, Yuchun Ding, Joseph Collin, David Steel, Natalio Krasnogor, Jumana Al-Aama, Susan Lindsay, Carla Mellough, Majlinda Lako
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied...
May 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29776148/asymmetry-in-cilia-configuration-induces-hydrodynamic-phase-locking
#2
Keiji Okumura, Seiya Nishikawa, Toshihiro Omori, Takuji Ishikawa, Atsuko Takamatsu
To gain insight into the nature of biological synchronization at the microscopic scale, we here investigate the hydrodynamic synchronization between conically rotating objects termed nodal cilia. A mechanical model of three rotating cilia is proposed with consideration of variation in their shapes and geometrical arrangement. We conduct numerical estimations of both near-field and far-field hydrodynamic interactions, and we apply a conventional averaging method for weakly coupled oscillators. In the nonidentical case, the three cilia showed stable locked-phase differences around ±π/2...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775042/bioinspired-synergy-sensor-chip-of-photonic-crystals-graphene-oxide-for-multi-amines-recognition
#3
Wanjie Ren, Meng Qin, Xiaotian Hu, Fengyu Li, Yuanfeng Wang, Yu Huang, Meng Su, Wenbo Li, Xin Qian, Kang-Lai Tang, Yanlin Song
Benefiting from the integrated functions of cilia and glomeruli in the olfactory system, animals can discriminate various odours even in hostile environments. Inspired by this synergetic system of response and signal processing units, a sensor chip of gra-phene oxide (GO) and photonic crystals (PCs) is fabricated. The GO aerogel functions like the olfactory cilia, which effectively captures the analytes and generates abundant sensing signals for recognition; and the PCs act as the olfactory glomeruli, whose periodic structure enables selective enhancement of the fluorescent signals to realize further signal processing...
May 18, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29771326/basal-exon-skipping-and-nonsense-associated-altered-splicing-allows-bypassing-complete-cep290-loss-of-function-in-individuals-with-unusually-mild-retinal-disease
#4
Iris Barny, Isabelle Perrault, Christel Michel, Mickael Soussan, Nicolas Goudin, Marlène Rio, Sophie Thomas, Tania Attié-Bitach, Christian Hamel, Hélène Dollfus, Josseline Kaplan, Jean-Michel Rozet, Xavier Gerard
CEP290 mutations cause a spectrum of ciliopathies from Leber congenital amaurosis type 10 (LCA10) to embryo-lethal Meckel syndrome (MKS). Using panel-based molecular diagnosis testing for inherited retinal diseases, we identified two individuals with some preserved vision despite biallelism for presumably truncating CEP290 mutations. The first one carried a homozygous 1 base-pair deletion in exon 17, introducing a premature termination codon (PTC) in exon 18 (c.1666del; p.Ile556Phefs*17). mRNA analysis revealed a basal exon skipping (BES) of exon 18, providing mutant cells with the ability to escape protein truncation, while disrupting the reading frame in controls...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29771182/ciliogenesis-is-reciprocally-regulated-by-ppara-and-nr1h4-fxr-through-controlling-autophagy-in-vitro-and-in-vivo
#5
Zhi-Qiang Liu, Joon No Lee, Myeongjoo Son, Jae-Young Lim, Raghbendra Kumar Dutta, Yunash Maharjan, SeongAe Kwak, Goo Taeg Oh, Kyunghee Byun, Seong-Kyu Choe, Raekil Park
The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated...
May 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29769531/myosin1d-is-an-evolutionarily-conserved-regulator-of-animal-left-right-asymmetry
#6
Thomas Juan, Charles Géminard, Jean-Baptiste Coutelis, Delphine Cerezo, Sophie Polès, Stéphane Noselli, Maximilian Fürthauer
The establishment of left-right (LR) asymmetry is fundamental to animal development, but the identification of a unifying mechanism establishing laterality across different phyla has remained elusive. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish. Alternatively, LR asymmetry can be established independently of cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton. Here, we show that Myosin1D (Myo1D), a previously identified regulator of Drosophila LR asymmetry, is essential for the formation and function of the zebrafish LR organizer (LRO), Kupffer's vesicle (KV)...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29767548/disruption-of-chloroplast-function-through-downregulation-of-phytoene-desaturase-enhances-the-systemic-accumulation-of-an-aphid-borne-phloem-restricted-virus
#7
Stacy L DeBlasio, Ana Rita Rebelo, Katherine Parks, Stewart Gray, Michelle Cilia
Chloroplasts play a central role in pathogen defense in plants. However, the majority of studies explaining the relationship between pathogens and chloroplasts have focused on pathogens that infect mesophyll cells. In contrast, the family Luteoviridae comprises RNA viruses that replicate and traffic exclusively in the phloem. Recently, our lab has shown that Potato leafroll virus (PLRV), the type species in the genus Polerovirus, forms an extensive interaction network with chloroplast-localized proteins, which is partially dependent on the PLRV capsid readthrough domain (RTD)...
May 16, 2018: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29761930/multiple-phosphorylation-sites-on-%C3%AE-tubulin-are-essential-and-contribute-to-the-biogenesis-of-basal-bodies-in-tetrahymena
#8
Ewa Joachimiak, Maria Jerka-Dziadosz, Łucja Krzemień-Ojak, Ewa Wacławek, Katarzyna Jedynak, Paulina Urbanska, Wojciech Brutkowski, Hanna Sas-Nowosielska, Hanna Fabczak, Jacek Gaertig, Dorota Wloga
The mechanisms that regulate γ-tubulin, including its post-translational modifications, are poorly understood. γ-Tubulin is important for the duplication of centrioles and structurally similar basal bodies (BBs), organelles which contain a ring of nine triplet microtubules. The ciliate Tetrahymena thermophila carries hundreds of cilia in a single cell and provides an excellent model to specifically address the role of γ-tubulin in the BBs assembly and maintenance. The genome of Tetrahymena contains a single γ-tubulin gene...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29758252/depression-resistant-phenotype-in-mice-overexpressing-regulator-of-g-protein-signaling-8-rgs8
#9
Yuki Kobayashi, Risa Takemoto, Shogo Yamato, Tomoya Okada, Michihiko Iijima, Yoshikatsu Uematsu, Shigeyuki Chaki, Yumiko Saito
Regulator of G protein signaling (RGS) proteins are negative regulators of heterotrimeric G proteins that act by accelerating Gα-mediated GTPase activity to terminate G protein-coupled receptor-associated signaling. RGS8 is expressed in several brain regions involved with movement and mood. To investigate the role of RGS8 in vivo, we generated transgenic mice overexpressing brain RGS8 (RGS8tg). RGS8 gene and protein expressions were examined by real-time PCR and immunohistochemistry, respectively, and a significant increase in RGS8 protein was detected in the hippocampal CA1 region compared with wild-type mice (WT)...
May 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29754569/toward-personalized-medicine-in-bardet-biedl-syndrome
#10
Joanna Kenny, Elizabeth Forsythe, Philip Beales, Chiara Bacchelli
Personalized medicine is becoming routine in the treatment of common diseases such as cancer, but has lagged behind in the field of rare diseases. It is currently in the early stages for the treatment of Bardet-Biedl syndrome. Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner. Owing to their structure and function, cilia provide an attractive therapeutic target and genetic therapies are being explored in ciliopathy treatment...
September 2017: Personalized Medicine
https://www.readbyqxmd.com/read/29752437/caspase-mediated-cleavage-of-the-centrosomal-proteins-during-apoptosis
#11
Mi Young Seo, Kunsoo Rhee
The centrosome is the major microtubule-organizing center and plays important roles in intracellular transport, cellular morphology, and motility. In mitotic cells, centrosomes function as spindle poles to pull a set of chromosomes into daughter cells. In quiescent cells, primary cilia are originated from the centrosomes. Given its involvement in various cellular processes, it is little surprising that the organelle would also participate in apoptotic events. However, it remains elusive how the centrosome changes in structure and organization during apoptosis...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748385/activation-of-airway-epithelial-bitter-taste-receptors-by-pseudomonas-aeruginosa-quinolones-modulates-calcium-cyclic-amp-and-nitric-oxide-signaling
#12
Jenna R Freund, Corrine J Mansfield, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Danielle R Reed, Peihua Jiang, Robert J Lee
Bitter taste receptors (T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We showed previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2Rs 4, 14, 16, and 38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29745101/simulations-of-centriole-of-polarized-centrosome-as-a-monopole-antenna-in-immune-and-viral-synapses
#13
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/29743676/reconstitution-reveals-motor-activation-for-intraflagellar-transport
#14
Mohamed A A Mohamed, Willi L Stepp, Zeynep Ökten
The human body represents a notable example of ciliary diversification. Extending from the surface of most cells, cilia accomplish a diverse set of tasks. Predictably, mutations in ciliary genes cause a wide range of human diseases such as male infertility and blindness. In Caenorhabditis elegans sensory cilia, this functional diversity appears to be traceable to the differential regulation of the kinesin-2-powered intraflagellar-transport (IFT) machinery. Here we reconstituted the first, to our knowledge, functional multi-component IFT complex that is deployed in the sensory cilia of C...
May 9, 2018: Nature
https://www.readbyqxmd.com/read/29743590/loss-of-function-of-ift88-determines-metabolic-phenotypes-in-thyroid-cancer
#15
Junguee Lee, Shinae Yi, Minho Won, Young Shin Song, Hyon-Seung Yi, Young Joo Park, Ki Cheol Park, Jung Tae Kim, Joon Young Chang, Min Joung Lee, Hae Joung Sul, Ji Eun Choi, Koon Soon Kim, Jukka Kero, Joon Kim, Minho Shong
Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29742020/actin-dependent-regulation-of-cilia-length-by-the-inverted-formin-fhdc1
#16
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/29742019/the-e3-ubiquitin-ligase-ubr5-regulates-centriolar-satellite-stability-and-primary-cilia
#17
Robert F Shearer, Kari-Anne Myrum Frikstad, Jessie McKenna, Rachael A McCloy, Niantao Deng, Andrew Burgess, Trond Stokke, Sebastian Patzke, Darren N Saunders
Primary cilia are crucial for signal transduction in a variety of pathways, including Hedgehog and Wnt. Disruption of primary cilia formation (ciliogenesis) is linked to numerous developmental disorders (known as ciliopathies) and diseases, including cancer. The Ubiquitin-Proteasome System (UPS) component UBR5 was previously identified as a putative positive regulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 Ubiquitin ligase that is frequently deregulated in tumours, but its biological role in cancer is largely uncharacterised, partly due to a lack of understanding of interacting proteins and pathways...
May 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29741637/microscopic-analysis-of-sperm-movement-links-to-mechanisms-and-protein-components
#18
Kazuo Inaba, Kogiku Shiba
Cilia and flagella are cell machines that power hydrodynamic forces by fast beating. They are composed of bundles of 9 + 2 microtubules that associate with several protein structures including axonemal dyneins and their regulators. Spermatozoa are single cells with in most cases a single flagellum and are good cell models to study how flagellar movements are regulated and linked to cell behavior. In addition, the assessment of sperm motility is an important diagnostic tool for evaluating male fertility in human reproductive medicine, and in livestock and fisheries sciences...
May 8, 2018: Microscopy
https://www.readbyqxmd.com/read/29741156/systematic-studies-of-all-pih-proteins-in-zebrafish-reveal-their-distinct-roles-in-axonemal-dynein-assembly
#19
Hiroshi Yamaguchi, Toshiyuki Oda, Masahide Kikkawa, Hiroyuki Takeda
Construction of motile cilia/flagella requires cytoplasmic preassembly of axonemal dyneins before transport into cilia. Axonemal dyneins have various subtypes, but the roles of each dynein subtype and their assembly processes remain elusive in vertebrates. The PIH protein family, consisting of four members, has been implicated in the assembly of different dynein subtypes, although evidence for this idea is sparse. Here, we established zebrafish mutants of all four PIH-protein genes: pih1d1 , pih1d2 , ktu , and twister , and analyzed the structures of axonemal dyneins in mutant spermatozoa by cryo-electron tomography...
May 9, 2018: ELife
https://www.readbyqxmd.com/read/29740017/atoh1-rfx1-rfx3-transcription-factors-facilitate-the-differentiation-and-characterisation-of-inner-ear-hair-cell-like-cells-from-patient-specific-induced-pluripotent-stem-cells-harbouring-a8344g-mutation-of-mitochondrial-dna
#20
Yen-Chun Chen, Chia-Ling Tsai, Yau-Huei Wei, Yu-Ting Wu, Wei-Ting Hsu, Hung-Ching Lin, Yi-Chao Hsu
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles...
April 19, 2018: Cell Death & Disease
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