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  • 1
    Publication Date: 2008-05-30
    Description: The problem of finding the most efficient way to pack spheres has a long history, dating back to the crystalline arrays conjectured by Kepler and the random geometries explored by Bernal. Apart from its mathematical interest, the problem has practical relevance in a wide range of fields, from granular processing to fruit packing. There are currently numerous experiments showing that the loosest way to pack spheres (random loose packing) gives a density of approximately 55 per cent. On the other hand, the most compact way to pack spheres (random close packing) results in a maximum density of approximately 64 per cent. Although these values seem to be robust, there is as yet no physical interpretation for them. Here we present a statistical description of jammed states in which random close packing can be interpreted as the ground state of the ensemble of jammed matter. Our approach demonstrates that random packings of hard spheres in three dimensions cannot exceed a density limit of approximately 63.4 per cent. We construct a phase diagram that provides a unified view of the hard-sphere packing problem and illuminates various data, including the random-loose-packed state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Chaoming -- Wang, Ping -- Makse, Hernan A -- England -- Nature. 2008 May 29;453(7195):629-32. doi: 10.1038/nature06981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Levich Institute and Physics Department, City College of New York, New York, New York 10031, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509438" target="_blank"〉PubMed〈/a〉
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  • 2
    Publication Date: 2008-02-22
    Description: Phosphoinositides are a family of lipid signalling molecules that regulate many cellular functions in eukaryotes. Phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2), the central component in the phosphoinositide signalling circuitry, is generated primarily by type I phosphatidylinositol 4-phosphate 5-kinases (PIPKIalpha, PIPKIbeta and PIPKIgamma). In addition to functions in the cytosol, phosphoinositides are present in the nucleus, where they modulate several functions; however, the mechanism by which they directly regulate nuclear functions remains unknown. PIPKIs regulate cellular functions through interactions with protein partners, often PtdIns4,5P2 effectors, that target PIPKIs to discrete subcellular compartments, resulting in the spatial and temporal generation of PtdIns4,5P2 required for the regulation of specific signalling pathways. Therefore, to determine roles for nuclear PtdIns4,5P2 we set out to identify proteins that interacted with the nuclear PIPK, PIPKIalpha. Here we show that PIPKIalpha co-localizes at nuclear speckles and interacts with a newly identified non-canonical poly(A) polymerase, which we have termed Star-PAP (nuclear speckle targeted PIPKIalpha regulated-poly(A) polymerase) and that the activity of Star-PAP can be specifically regulated by PtdIns4,5P2. Star-PAP and PIPKIalpha function together in a complex to control the expression of select mRNAs, including the transcript encoding the key cytoprotective enzyme haem oxygenase-1 (refs 8, 9) and other oxidative stress response genes by regulating the 3'-end formation of their mRNAs. Taken together, the data demonstrate a model by which phosphoinositide signalling works in tandem with complement pathways to regulate the activity of Star-PAP and the subsequent biosynthesis of its target mRNA. The results reveal a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellman, David L -- Gonzales, Michael L -- Song, Chunhua -- Barlow, Christy A -- Wang, Ping -- Kendziorski, Christina -- Anderson, Richard A -- R01 GM051968/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Feb 21;451(7181):1013-7. doi: 10.1038/nature06666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular and Cellular Pharmacology, University of Wisconsin Medical School, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288197" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Nucleus/enzymology/genetics/*metabolism ; Heme Oxygenase-1/genetics ; Humans ; Mice ; Multiprotein Complexes/metabolism ; Oxidative Stress/genetics ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositol Phosphates/*metabolism ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/genetics/metabolism ; Polynucleotide Adenylyltransferase/chemistry/deficiency/genetics/*metabolism ; Protein Binding ; *RNA 3' End Processing ; RNA, Messenger/genetics/metabolism ; Substrate Specificity ; Transcription, Genetic
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  • 3
    Publication Date: 2008-02-08
    Description: Holographic three-dimensional (3D) displays provide realistic images without the need for special eyewear, making them valuable tools for applications that require situational awareness, such as medical, industrial and military imaging. Currently commercially available holographic 3D displays use photopolymers that lack image-updating capability, resulting in restricted use and high cost. Photorefractive polymers are dynamic holographic recording materials that allow updating of images and have a wide range of applications, including optical correlation, imaging through scattering media and optical communication. To be suitable for 3D displays, photorefractive polymers need to have nearly 100% diffraction efficiency, fast writing time, hours of image persistence, rapid erasure, and large area-a combination of properties that has not been shown before. Here, we report an updatable holographic 3D display based on photorefractive polymers with such properties, capable of recording and displaying new images every few minutes. This is the largest photorefractive 3D display to date (4 x 4 inches in size); it can be recorded within a few minutes, viewed for several hours without the need for refreshing, and can be completely erased and updated with new images when desired.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tay, Savas -- Blanche, P-A -- Voorakaranam, R -- Tunc, A V -- Lin, W -- Rokutanda, S -- Gu, T -- Flores, D -- Wang, P -- Li, G -- St Hilaire, P -- Thomas, J -- Norwood, R A -- Yamamoto, M -- Peyghambarian, N -- England -- Nature. 2008 Feb 7;451(7179):694-8. doi: 10.1038/nature06596.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Optical Sciences, University of Arizona, Tucson, Arizona 85721, USA. savas.tay@optics.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256667" target="_blank"〉PubMed〈/a〉
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  • 4
    Publication Date: 2008-06-20
    Description: Dinitrogen (N(2)) fixation is widely recognized as an important process in controlling ecosystem responses to global environmental change, both today and in the past; however, significant discrepancies exist between theory and observations of patterns of N(2) fixation across major sectors of the land biosphere. A question remains as to why symbiotic N(2)-fixing plants are more abundant in vast areas of the tropics than in many of the mature forests that seem to be nitrogen-limited in the temperate and boreal zones. Here we present a unifying framework for terrestrial N(2) fixation that can explain the geographic occurrence of N(2) fixers across diverse biomes and at the global scale. By examining trade-offs inherent in plant carbon, nitrogen and phosphorus capture, we find a clear advantage to symbiotic N(2) fixers in phosphorus-limited tropical savannas and lowland tropical forests. The ability of N(2) fixers to invest nitrogen into phosphorus acquisition seems vital to sustained N(2) fixation in phosphorus-limited tropical ecosystems. In contrast, modern-day temperatures seem to constrain N(2) fixation rates and N(2)-fixing species from mature forests in the high latitudes. We propose that an analysis that couples biogeochemical cycling and biophysical mechanisms is sufficient to explain the principal geographical patterns of symbiotic N(2) fixation on land, thus providing a basis for predicting the response of nutrient-limited ecosystems to climate change and increasing atmospheric CO(2).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Houlton, Benjamin Z -- Wang, Ying-Ping -- Vitousek, Peter M -- Field, Christopher B -- England -- Nature. 2008 Jul 17;454(7202):327-30. doi: 10.1038/nature07028. Epub 2008 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Sciences, Stanford University, Stanford, California 94305, USA. bzhoulton@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563086" target="_blank"〉PubMed〈/a〉
    Keywords: *Ecosystem ; Models, Biological ; *Nitrogen Fixation ; Nitrogenase/metabolism ; Phosphates/metabolism ; Phosphoric Monoester Hydrolases/metabolism ; Plants/enzymology/*metabolism ; Soil/analysis ; Symbiosis ; Temperature ; Tropical Climate
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  • 5
    Publication Date: 2009-10-30
    Description: A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximately 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximately 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves. Here we report the detection of emission up to approximately 31 GeV from the distant and short GRB 090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space-time on a very small scale linearly alters the speed of light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abdo, A A -- Ackermann, M -- Ajello, M -- Asano, K -- Atwood, W B -- Axelsson, M -- Baldini, L -- Ballet, J -- Barbiellini, G -- Baring, M G -- Bastieri, D -- Bechtol, K -- Bellazzini, R -- Berenji, B -- Bhat, P N -- Bissaldi, E -- Bloom, E D -- Bonamente, E -- Bonnell, J -- Borgland, A W -- Bouvier, A -- Bregeon, J -- Brez, A -- Briggs, M S -- Brigida, M -- Bruel, P -- Burgess, J M -- Burnett, T H -- Caliandro, G A -- Cameron, R A -- Caraveo, P A -- Casandjian, J M -- Cecchi, C -- Celik, O -- Chaplin, V -- Charles, E -- Cheung, C C -- Chiang, J -- Ciprini, S -- Claus, R -- Cohen-Tanugi, J -- Cominsky, L R -- Connaughton, V -- Conrad, J -- Cutini, S -- Dermer, C D -- de Angelis, A -- de Palma, F -- Digel, S W -- Dingus, B L -- do Couto E Silva, E -- Drell, P S -- Dubois, R -- Dumora, D -- Farnier, C -- Favuzzi, C -- Fegan, S J -- Finke, J -- Fishman, G -- Focke, W B -- Foschini, L -- Fukazawa, Y -- Funk, S -- Fusco, P -- Gargano, F -- Gasparrini, D -- Gehrels, N -- Germani, S -- Gibby, L -- Giebels, B -- Giglietto, N -- Giordano, F -- Glanzman, T -- Godfrey, G -- Granot, J -- Greiner, J -- Grenier, I A -- Grondin, M-H -- Grove, J E -- Grupe, D -- Guillemot, L -- Guiriec, S -- Hanabata, Y -- Harding, A K -- Hayashida, M -- Hays, E -- Hoversten, E A -- Hughes, R E -- Johannesson, G -- Johnson, A S -- Johnson, R P -- Johnson, W N -- Kamae, T -- Katagiri, H -- Kataoka, J -- Kawai, N -- Kerr, M -- Kippen, R M -- Knodlseder, J -- Kocevski, D -- Kouveliotou, C -- Kuehn, F -- Kuss, M -- Lande, J -- Latronico, L -- Lemoine-Goumard, M -- Longo, F -- Loparco, F -- Lott, B -- Lovellette, M N -- Lubrano, P -- Madejski, G M -- Makeev, A -- Mazziotta, M N -- McBreen, S -- McEnery, J E -- McGlynn, S -- Meszaros, P -- Meurer, C -- Michelson, P F -- Mitthumsiri, W -- Mizuno, T -- Moiseev, A A -- Monte, C -- Monzani, M E -- Moretti, E -- Morselli, A -- Moskalenko, I V -- Murgia, S -- Nakamori, T -- Nolan, P L -- Norris, J P -- Nuss, E -- Ohno, M -- Ohsugi, T -- Omodei, N -- Orlando, E -- Ormes, J F -- Ozaki, M -- Paciesas, W S -- Paneque, D -- Panetta, J H -- Parent, D -- Pelassa, V -- Pepe, M -- Pesce-Rollins, M -- Petrosian, V -- Piron, F -- Porter, T A -- Preece, R -- Raino, S -- Ramirez-Ruiz, E -- Rando, R -- Razzano, M -- Razzaque, S -- Reimer, A -- Reimer, O -- Reposeur, T -- Ritz, S -- Rochester, L S -- Rodriguez, A Y -- Roth, M -- Ryde, F -- Sadrozinski, H F-W -- Sanchez, D -- Sander, A -- Saz Parkinson, P M -- Scargle, J D -- Schalk, T L -- Sgro, C -- Siskind, E J -- Smith, D A -- Smith, P D -- Spandre, G -- Spinelli, P -- Stamatikos, M -- Stecker, F W -- Strickman, M S -- Suson, D J -- Tajima, H -- Takahashi, H -- Takahashi, T -- Tanaka, T -- Thayer, J B -- Thayer, J G -- Thompson, D J -- Tibaldo, L -- Toma, K -- Torres, D F -- Tosti, G -- Troja, E -- Uchiyama, Y -- Uehara, T -- Usher, T L -- van der Horst, A J -- Vasileiou, V -- Vilchez, N -- Vitale, V -- von Kienlin, A -- Waite, A P -- Wang, P -- Wilson-Hodge, C -- Winer, B L -- Wood, K S -- Wu, X F -- Yamazaki, R -- Ylinen, T -- Ziegler, M -- England -- Nature. 2009 Nov 19;462(7271):331-4. doi: 10.1038/nature08574. Epub 2009 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Space Science Division, Naval Research Laboratory, Washington, District of Columbia 20375, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865083" target="_blank"〉PubMed〈/a〉
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  • 6
    Publication Date: 2009-11-27
    Description: FocA is a representative member of the formate-nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. The structure and transport mechanism of the formate-nitrite transporter family remain unknown. Here we report the crystal structure of Escherichia coli FocA at 2.25 A resolution. FocA forms a symmetric pentamer, with each protomer consisting of six transmembrane segments. Despite a lack of sequence homology, the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel, rather than a transporter. Structural analysis identifies potentially important channel residues, defines the channel path and reveals two constriction sites. Unlike aquaporin, FocA is impermeable to water but allows the passage of formate. A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yi -- Huang, Yongjian -- Wang, Jiawei -- Cheng, Chao -- Huang, Weijiao -- Lu, Peilong -- Xu, Ya-Nan -- Wang, Pengye -- Yan, Nieng -- Shi, Yigong -- England -- Nature. 2009 Nov 26;462(7272):467-72. doi: 10.1038/nature08610.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Protein Science Laboratory, Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940917" target="_blank"〉PubMed〈/a〉
    Keywords: Aquaporins/*chemistry/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism ; Formates/metabolism ; Liposomes/chemistry/metabolism ; Membrane Transport Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; Molecular Mimicry ; Mutation ; Permeability ; Protein Structure, Quaternary ; Structure-Activity Relationship ; Water/analysis/metabolism
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  • 7
    Publication Date: 2012-11-23
    Description: Hydrophobic hydration is considered to have a key role in biological processes ranging from membrane formation to protein folding and ligand binding. Historically, hydrophobic hydration shells were thought to resemble solid clathrate hydrates, with solutes surrounded by polyhedral cages composed of tetrahedrally hydrogen-bonded water molecules. But more recent experimental and theoretical studies have challenged this view and emphasized the importance of the length scales involved. Here we report combined polarized, isotopic and temperature-dependent Raman scattering measurements with multivariate curve resolution (Raman-MCR) that explore hydrophobic hydration by mapping the vibrational spectroscopic features arising from the hydrophobic hydration shells of linear alcohols ranging from methanol to heptanol. Our data, covering the entire 0-100 degrees C temperature range, show clear evidence that at low temperatures the hydration shells have a hydrophobically enhanced water structure with greater tetrahedral order and fewer weak hydrogen bonds than the surrounding bulk water. This structure disappears with increasing temperature and is then, for hydrophobic chains longer than ~1 nm, replaced by a more disordered structure with weaker hydrogen bonds than bulk water. These observations support our current understanding of hydrophobic hydration, including the thermally induced water structural transformation that is suggestive of the hydrophobic crossover predicted to occur at lengths of ~1 nm (refs 5, 9, 10, 14).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, Joel G -- Gierszal, Kamil P -- Wang, Ping -- Ben-Amotz, Dor -- England -- Nature. 2012 Nov 22;491(7425):582-5. doi: 10.1038/nature11570.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Purdue University, Department of Chemistry, West Lafayette, Indiana 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23172216" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Butanol/chemistry ; Hydrogen Bonding ; *Hydrophobic and Hydrophilic Interactions ; Molecular Structure ; Spectrum Analysis, Raman ; Temperature ; Vibration ; Water/*chemistry
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  • 8
    Publication Date: 2014-07-22
    Description: Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249766/" 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/PMC4249766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Bing -- Wang, Jing -- Wang, Xiaojing -- Zhu, Jing -- Liu, Qi -- Shi, Zhiao -- Chambers, Matthew C -- Zimmerman, Lisa J -- Shaddox, Kent F -- Kim, Sangtae -- Davies, Sherri R -- Wang, Sean -- Wang, Pei -- Kinsinger, Christopher R -- Rivers, Robert C -- Rodriguez, Henry -- Townsend, R Reid -- Ellis, Matthew J C -- Carr, Steven A -- Tabb, David L -- Coffey, Robert J -- Slebos, Robbert J C -- Liebler, Daniel C -- NCI CPTAC -- GM088822/GM/NIGMS NIH HHS/ -- P30 CA068485/CA/NCI NIH HHS/ -- P30 DK058404/DK/NIDDK NIH HHS/ -- P30CA068485/CA/NCI NIH HHS/ -- P50 CA095103/CA/NCI NIH HHS/ -- P50CA095103/CA/NCI NIH HHS/ -- R01 GM088822/GM/NIGMS NIH HHS/ -- U24 CA159988/CA/NCI NIH HHS/ -- U24 CA160019/CA/NCI NIH HHS/ -- U24 CA160034/CA/NCI NIH HHS/ -- U24 CA160035/CA/NCI NIH HHS/ -- U24CA159988/CA/NCI NIH HHS/ -- U24CA160034/CA/NCI NIH HHS/ -- U24CA160035/CA/NCI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Sep 18;513(7518):382-7. doi: 10.1038/nature13438. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; 1] Advanced Computing Center for Research and Education, Vanderbilt University, Nashville, Tennessee 37232, USA [2] Department of Electrical Engineering and Computer Science, Vanderbilt University, Tennessee 37232, USA. ; 1] Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA. ; Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA. ; Directorate of Fundamental and Computational Sciences, Pacific Northwest National Laboratory, Richland, Washington 99352, USA. ; Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B500, Seattle, Washington 98109, USA. ; Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1498, New York, New York 10029, USA. ; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland 20892, USA. ; Broad Institute of MIT and Harvard, Cambridge, Maryland 02142, USA. ; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; 1] Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043054" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Human, Pair 20/genetics ; Colonic Neoplasms/*genetics/*metabolism ; CpG Islands/genetics ; DNA Copy Number Variations/genetics ; DNA Methylation ; *Genomics ; Hepatocyte Nuclear Factor 4/genetics ; Humans ; Microsatellite Repeats/genetics ; Mitochondrial Membrane Transport Proteins/genetics ; Mutation, Missense/genetics ; Neoplasm Proteins/analysis/genetics/metabolism ; Point Mutation/genetics ; Proteome/analysis/genetics/*metabolism ; Proteomics ; Proto-Oncogene Proteins pp60(c-src)/genetics ; RNA, Messenger/analysis/genetics/metabolism ; RNA, Neoplasm/analysis/genetics/metabolism ; Rectal Neoplasms/*genetics/*metabolism ; Transcriptome/*genetics
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  • 9
    Publication Date: 2015-11-03
    Description: DNA methylation is an important epigenetic modification. Ten-eleven translocation (TET) proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Here we show that human TET1 and TET2 are more active on 5mC-DNA than 5hmC/5fC-DNA substrates. We determine the crystal structures of TET2-5hmC-DNA and TET2-5fC-DNA complexes at 1.80 A and 1.97 A resolution, respectively. The cytosine portion of 5hmC/5fC is specifically recognized by TET2 in a manner similar to that of 5mC in the TET2-5mC-DNA structure, and the pyrimidine base of 5mC/5hmC/5fC adopts an almost identical conformation within the catalytic cavity. However, the hydroxyl group of 5hmC and carbonyl group of 5fC face towards the opposite direction because the hydroxymethyl group of 5hmC and formyl group of 5fC adopt restrained conformations through forming hydrogen bonds with the 1-carboxylate of NOG and N4 exocyclic nitrogen of cytosine, respectively. Biochemical analyses indicate that the substrate preference of TET2 results from the different efficiencies of hydrogen abstraction in TET2-mediated oxidation. The restrained conformation of 5hmC and 5fC within the catalytic cavity may prevent their abstractable hydrogen(s) adopting a favourable orientation for hydrogen abstraction and thus result in low catalytic efficiency. Our studies demonstrate that the substrate preference of TET2 results from the intrinsic value of its substrates at their 5mC derivative groups and suggest that 5hmC is relatively stable and less prone to further oxidation by TET proteins. Therefore, TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate the generation of 5hmC as a potentially stable mark for regulatory functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Lulu -- Lu, Junyan -- Cheng, Jingdong -- Rao, Qinhui -- Li, Ze -- Hou, Haifeng -- Lou, Zhiyong -- Zhang, Lei -- Li, Wei -- Gong, Wei -- Liu, Mengjie -- Sun, Chang -- Yin, Xiaotong -- Li, Jie -- Tan, Xiangshi -- Wang, Pengcheng -- Wang, Yinsheng -- Fang, Dong -- Cui, Qiang -- Yang, Pengyuan -- He, Chuan -- Jiang, Hualiang -- Luo, Cheng -- Xu, Yanhui -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Nov 5;527(7576):118-22. doi: 10.1038/nature15713. Epub 2015 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. ; Key Laboratory of Molecular Medicine, Ministry of Education, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. ; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China. ; Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. ; Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. ; Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China. ; MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, China. ; Department of Chemistry, University of California-Riverside, Riverside, California 92521-0403, USA. ; Theoretical Chemistry Institute, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA. ; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26524525" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Cytosine/analogs & derivatives/metabolism ; DNA/*chemistry/*metabolism ; DNA Methylation ; DNA-Binding Proteins/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Models, Molecular ; Oxidation-Reduction ; Protein Binding ; Proto-Oncogene Proteins/*chemistry/*metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2011-07-15
    Description: Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Facciabene, Andrea -- Peng, Xiaohui -- Hagemann, Ian S -- Balint, Klara -- Barchetti, Andrea -- Wang, Li-Ping -- Gimotty, Phyllis A -- Gilks, C Blake -- Lal, Priti -- Zhang, Lin -- Coukos, George -- P01-CA83638/CA/NCI NIH HHS/ -- R01-CA116779/CA/NCI NIH HHS/ -- England -- Nature. 2011 Jul 13;475(7355):226-30. doi: 10.1038/nature10169.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21753853" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Hypoxia/genetics ; Cell Line, Tumor ; Chemokines, CC/genetics/*metabolism ; Culture Media, Conditioned/pharmacology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immune Tolerance/*immunology ; Mice ; Mice, Inbred C57BL ; *Neovascularization, Pathologic ; Ovarian Neoplasms/*blood supply/immunology/*metabolism/pathology ; Receptors, CCR10/metabolism ; T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism ; Vascular Endothelial Growth Factor A/metabolism/secretion
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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