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  • 1
    Publication Date: 2013-10-04
    Description: The primary cilium is a microtubule-based organelle that functions in sensory and signalling pathways. Defects in ciliogenesis can lead to a group of genetic syndromes known as ciliopathies. However, the regulatory mechanisms of primary ciliogenesis in normal and cancer cells are incompletely understood. Here we demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral-facial-digital syndrome 1), at centriolar satellites promotes primary cilium biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles and protein aggregates are engulfed in autophagosomes and delivered to lysosomes for destruction. We show that the population of OFD1 at the centriolar satellites is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient Atg5 or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar satellites, leading to fewer and shorter primary cilia and a defective recruitment of BBS4 (Bardet-Biedl syndrome 4) to cilia. These defects are fully rescued by OFD1 partial knockdown that reduces the population of OFD1 at centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites promotes cilia formation in both cycling cells and transformed breast cancer MCF7 cells that normally do not form cilia. This work reveals that removal of OFD1 by autophagy at centriolar satellites represents a general mechanism to promote ciliogenesis in mammalian cells. These findings define a newly recognized role of autophagy in organelle biogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075283/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075283/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Zaiming -- Lin, Mary Grace -- Stowe, Timothy Richard -- Chen, She -- Zhu, Muyuan -- Stearns, Tim -- Franco, Brunella -- Zhong, Qing -- CA133228/CA/NCI NIH HHS/ -- R01 CA133228/CA/NCI NIH HHS/ -- TGM11CB3/Telethon/Italy -- England -- Nature. 2013 Oct 10;502(7470):254-7. doi: 10.1038/nature12606. Epub 2013 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24089205" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy/genetics ; Cell Line ; Centrioles/*metabolism ; Cilia/genetics/metabolism/*physiology ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; MCF-7 Cells ; Mice ; Protein Transport ; Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-02-18
    Description: Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442024/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442024/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diao, Jiajie -- Liu, Rong -- Rong, Yueguang -- Zhao, Minglei -- Zhang, Jing -- Lai, Ying -- Zhou, Qiangjun -- Wilz, Livia M -- Li, Jianxu -- Vivona, Sandro -- Pfuetzner, Richard A -- Brunger, Axel T -- Zhong, Qing -- 5P30CA142543/CA/NCI NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 CA133228/CA/NCI NIH HHS/ -- R01 R37-MH63105/MH/NIMH NIH HHS/ -- R37 MH063105/MH/NIMH NIH HHS/ -- T32 GM007232/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Apr 23;520(7548):563-6. doi: 10.1038/nature14147. Epub 2015 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. ; 1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [3] College of Food Science &Nutritional Engineering, China Agricultural University, Beijing 100083, China. ; 1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25686604" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/*chemistry/*metabolism ; *Autophagy ; Endosomes/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Lysosomes/*metabolism ; *Membrane Fusion ; Phagosomes/chemistry/*metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Qa-SNARE Proteins/metabolism ; Qb-SNARE Proteins/metabolism ; Qc-SNARE Proteins/metabolism ; R-SNARE Proteins/metabolism ; SNARE Proteins/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Abstract: Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.
    Type of Publication: Journal article published
    PubMed ID: 28596378
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  • 4
    Abstract: Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3'-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.
    Type of Publication: Journal article published
    PubMed ID: 29563550
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  • 5
    ISSN: 0264-410X
    Keywords: Env ; Gag ; Human immunodeficiency virus ; cytotoxic T lymphocyte ; delayed-type hypersensitivity
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0013-4686
    Keywords: Li-ion cells ; carbon anodes ; intercalation ; lithium intercalated carbon.
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: An approach for the localization and characterization of electrically active defects in multicrystalline silicon and of artefacts in photovoltaic devices is presented. The essential idea of the method is the noninvasive magnetic detection of photocurrents generated in the sample by local illumination. Magnetic imaging with high spatial and magnetic resolution is performed by scanning the sample under investigation and synchronously measuring the magnetic field of the photocurrents using highly sensitive superconducting quantum interference device magnetometers. The technique enables the nondestructive and nonpolluting detection and investigation of electrically active grain boundaries in multicrystalline silicon wafers. Results obtained from photovoltaic devices show that typical, performance-limiting defects can be localized, as they cause distinct features in the magnetic field topography. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 68 (2003), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Tap water and 1% CMC solutions were heated in a 40.68 MHz, 30 kW continuous flow radio frequency unit. Temperatures at different vertical and radial locations were monitored by fiber optic probes during batch heating of tap water and 1% CMC solution. Temperatures at different locations were similar during batch heating of tap water, while a significant temperature difference was observed for 1% CMC solutions, with the temperature close to the wall being higher than that at the center. Similar trends were observed during continuous heating of tap water and 1% CMC solutions, with Twall 〉 TR/2 〉 Tcenter for the latter. The observations were a result of different dielectric properties of these 2 fluids, as well as the fluid flow characteristics during continuous heating.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 110 (1999), S. 192-196 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Because of the dispute in the literature over the dissociation rate and energy partitioning of the acetone molecule upon photoexcitation to the S1 state (π*←n) and 3s Rydberg state (3s←n), we have remeasured the lifetime of acetone (also d6-acetone) on the S1 and 3s surfaces by a femtosecond time-resolved multiphoton ionization technique, coupled with a reflectron time-of-flight mass spectrometer. The measured dissociation rate of acetone on the S1 surface is prompt, and the acetyl radical is long lived. The lifetime of acetone on the 3s surface is measured to be 3.2±0.4 ps (6.0±0.5 ps for d6-acetone). The dissociation rate of acetyl is approximately 1.7 ps (2.5 ps for d3-acetyl) from the curve fitting. This agrees well with the Rice–Ramsperger–Kassel–Marcus theory predicted lifetime of 1.0 ps (1.9 ps for d3-acetyl) when the internal excitation energy of the acetyl radical is treated by a statistical-adiabatic-impulsive model. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 110 (1999), S. 6257-6267 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: The study of the interaction of femtosecond laser radiation with matter, especially clusters, has blossomed in recent years due to advances in laser technology. One aspect of this interaction is Coulomb explosion. This effect occurs when the repulsive energy of like charges, known as Coulomb repulsion, overcomes the cluster's total cohesive energy, causing the cluster to disintegrate into charged fragments. In this study, the interactions of methyl iodide clusters, formed in a supersonic expansion using argon and helium as carrier gases, were investigated at 795 nm using a Ti:Sapphire femtosecond laser. The resulting atomic and cluster ions were analyzed in a reflection time-of-flight mass spectrometer. The focus of these studies was the elucidation of the effects of carrier gas and laser wavelength on the laser-cluster interactions leading to Coulomb explosion. To achieve these goals, the effects of different carrier gases, laser power, cluster distribution, and the resulting Coulomb explosion energies were examined. A secondary consideration was to examine the experimental results with regard to the Coherent Electron Motion and Ionization Ignition models. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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