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https://www.readbyqxmd.com/read/28912135/editorial-expression-of-concern
#1
EDITORIAL
Jeremy Berg
No abstract text is available yet for this article.
September 14, 2017: Science
https://www.readbyqxmd.com/read/28912134/zatt-znf451-mediated-resolution-of-topoisomerase-2-dna-protein-cross-links
#2
Matthew J Schellenberg, Jenna Ariel Lieberman, Andrés Herrero-Ruiz, Logan R Butler, Jason G Williams, Ana M Muñoz-Cabello, Geoffrey A Mueller, Robert E London, Felipe Cortés-Ledesma, R Scott Williams
Topoisomerase 2 (TOP2) DNA transactions are essential for life, and proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28912133/use-of-crispr-modified-human-stem-cell-organoids-to-study-the-origin-of-mutational-signatures-in-cancer
#3
Jarno Drost, Ruben van Boxtel, Francis Blokzijl, Tomohiro Mizutani, Nobuo Sasaki, Valentina Sasselli, Joep de Ligt, Sam Behjati, Judith E Grolleman, Tom van Wezel, Serena Nik-Zainal, Roland P Kuiper, Edwin Cuppen, Hans Clevers
Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology, and hold diagnostic and prognostic value. Here, we develop a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR/Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed sub-cloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair-deficient colorectal cancers...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28912132/mitotic-transcription-and-waves-of-gene-reactivation-during-mitotic-exit
#4
Katherine C Palozola, Greg Donahue, Hong Liu, Gregory R Grant, Justin S Becker, Allison Cote, Hongtao Yu, Arjun Raj, Kenneth S Zaret
Although the genome is generally thought to be transcriptionally silent during mitosis, technical limitations have prevented sensitive mapping of transcription during mitosis and mitotic exit. Thus, the means by which the interphase expression pattern is transduced to daughter cells have been unclear. We used 5-ethynyluridine to pulse-label transcripts during mitosis and mitotic exit and find that many genes exhibit transcription during mitosis, as confirmed by FITC-UTP labeling, RNA FISH, and RT-qPCR. The first round of transcription immediately following mitosis primarily activates genes involved in the growth and rebuilding of daughter cells, rather than cell type-specific functions...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28912131/imaging-the-halogen-bond-in-self-assembled-halogenbenzenes-on-silver
#5
Zhumin Han, Gregory Czap, Chi-Lun Chiang, Chen Xu, Peter J Wagner, Xinyuan Wei, Yanxing Zhang, Ruqian Wu, W Ho
Halogens are among the most electronegative elements, and the variations in size and polarizability of halogens require different descriptions of the intermolecular bonds they form. Here we use the inelastic tunneling probe (itProbe) to acquire real-space imaging of intermolecular bonding structures in the two-dimensional self-assembly of halogenbenzene molecules on a metal surface. Direct visualization is obtained for the intermolecular attraction and the "windmill" pattern of bonding among the fully halogenated molecules...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28882997/dopamine-oxidation-mediates-mitochondrial-and-lysosomal-dysfunction-in-parkinson-s-disease
#6
Lena F Burbulla, Pingping Song, Joseph R Mazzulli, Enrico Zampese, Yvette C Wong, Sohee Jeon, David P Santos, Judith Blanz, Carolin D Obermaier, Chelsee Strojny, Jeffrey N Savas, Evangelos Kiskinis, Xiaoxi Zhuang, Rejko Krüger, D James Surmeier, Dimitri Krainc
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation, ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction and α-synuclein accumulation...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28882996/fibril-structure-of-amyloid-%C3%A3-1-42-by-cryoelectron-microscopy
#7
Lothar Gremer, Daniel Schölzel, Carla Schenk, Elke Reinartz, Jörg Labahn, Raimond B G Ravelli, Markus Tusche, Carmen Lopez-Iglesias, Wolfgang Hoyer, Henrike Heise, Dieter Willbold, Gunnar F Schröder
Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryoelectron microscopy (cryo-EM) to 4.0 Å resolution, complemented by solid-state nuclear magnetic resonance (NMR) experiments. The backbone of all 42 residues and nearly all sidechains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28882995/aqueous-au-pd-colloids-catalyze-selective-ch4-oxidation-to-ch3oh-with-o2-under-mild-conditions
#8
Nishtha Agarwal, Simon J Freakley, Rebecca U McVicker, Sultan M Althahban, Nikolaos Dimitratos, Qian He, David J Morgan, Robert L Jenkins, David J Willock, Stuart H Taylor, Christopher J Kiely, Graham J Hutchings
The selective oxidation of methane, the primary component of natural gas, remains an important challenge in catalysis. Using colloidal gold-palladium nanoparticles rather than the same nanoparticles supported on titanium oxide, we oxidized methane to methanol with high selectivity (92%) in aqueous solution at mild temperatures. Using isotopically labeled O2 as an oxidant in the presence of H2O2, we demonstrate that the methanol produced incorporated a substantial fraction (70%) of gas-phase O2 More oxygenated products were formed than H2O2 consumed, suggesting that the controlled breakdown of H2O2 activates methane which subsequently incorporates molecular oxygen through a radical process...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28882994/synthesis-of-mixed-hypermetallic-oxide-baoca-from-laser-cooled-reagents-in-an-atom-ion-hybrid-trap
#9
Prateek Puri, Michael Mills, Christian Schneider, Ionel Simbotin, John A Montgomery, Robin Côté, Arthur G Suits, Eric R Hudson
Hypermetallic alkaline earth (M) oxides of formula MOM have been studied under plasma conditions that preclude insight into their formation mechanism. We present here the application of emerging techniques in ultracold physics to the synthesis of a mixed hypermetallic oxide, BaOCa(+) These methods, augmented by high-level electronic structure calculations, permit detailed investigation of the bonding and structure, as well as the mechanism of its formation via the barrierless reaction of Ca ((3)PJ) with BaOCH3(+) Further investigations of the reaction kinetics as a function of collision energy over the range 0...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28882993/the-condensin-complex-is-a-mechanochemical-motor-that-translocates-along-dna
#10
Tsuyoshi Terakawa, Shveta Bisht, Jorine M Eeftens, Cees Dekker, Christian H Haering, Eric C Greene
Condensin plays crucial roles in chromosome organization and compaction, but the mechanistic basis for its functions remains obscure. Here, we use single-molecule imaging to demonstrate that Saccharomyces cerevisiae condensin is a molecular motor capable of ATP hydrolysis-dependent translocation along double-stranded DNA. Condensin's translocation activity is rapid and highly processive, with individual complexes traveling an average distance of ≥10 kilobases at a velocity of ~60 base pairs per second. Our results suggest that condensin may take steps comparable in length to its ~50-nanometer coiled-coil subunits, suggestive of a translocation mechanism that is distinct from any reported DNA motor protein...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28874501/retraction
#11
LETTER
Yuji Tanno, Hiroaki Susumu, Miyuki Kawamura, Haruhiko Sugimura, Takashi Honda, Yoshinori Watanabe
No abstract text is available yet for this article.
September 5, 2017: Science
https://www.readbyqxmd.com/read/28860209/the-drosophila-embryo-at-single-cell-transcriptome-resolution
#12
Nikos Karaiskos, Philipp Wahle, Jonathan Alles, Anastasiya Boltengagen, Salah Ayoub, Claudia Kipar, Christine Kocks, Nikolaus Rajewsky, Robert P Zinzen
By the onset of morphogenesis, Drosophila embryos consist of about 6000 cells that express distinct gene combinations. Here, we used single-cell sequencing of precisely staged embryos and devised DistMap, a computational mapping strategy to reconstruct the embryo and to predict spatial gene expression approaching single-cell resolution. We produce a virtual embryo with about 8000 expressed genes per cell. Our interactive "Drosophila-Virtual-Expression-eXplorer" (DVEX) database generates three-dimensional virtual in situ hybridizations and computes gene expression gradients...
August 31, 2017: Science
https://www.readbyqxmd.com/read/28860208/nanophotonic-rare-earth-quantum-memory-with-optically-controlled-retrieval
#13
Tian Zhong, Jonathan M Kindem, John G Bartholomew, Jake Rochman, Ioana Craiciu, Evan Miyazono, Marco Bettinelli, Enrico Cavalli, Varun Verma, Sae Woo Nam, Francesco Marsili, Matthew D Shaw, Andrew D Beyer, Andrei Faraon
Optical quantum memories are essential elements in quantum networks for long distance distribution of quantum entanglement. Scalable development of quantum network nodes requires on-chip qubit storage functionality with control of its readout time. We demonstrate a high-fidelity nanophotonic quantum memory based on a mesoscopic neodymium ensemble coupled to a photonic crystal cavity. The nanocavity enables >95% spin polarization for efficient initialization of the atomic frequency comb memory, and time-bin-selective readout via enhanced optical Stark shift of the comb frequencies...
August 31, 2017: Science
https://www.readbyqxmd.com/read/28860207/paf1-regulation-of-promoter-proximal-pause-release-via-enhancer-activation
#14
Fei Xavier Chen, Peng Xie, Clayton K Collings, Kaixiang Cao, Yuki Aoi, Stacy A Marshall, Emily J Rendleman, Michal Ugarenko, Patrick A Ozark, Anda Zhang, Ramin Shiekhattar, Edwin R Smith, Michael Q Zhang, Ali Shilatifard
Gene expression in metazoans is regulated by RNA Polymerase II (Pol II) promoter-proximal pausing and its release. Previously, we identified that Pol II-associated factor 1 (PAF1) modulates the release of paused Pol II into productive elongation. Here, we find that PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of these enhancers. Enhancer activation as the result of Paf1 loss releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates the release of paused Pol II on PAF1 target genes without major interference in the establishment of pausing at their cognate promoters...
August 31, 2017: Science
https://www.readbyqxmd.com/read/28860206/protecting-unauthorized-immigrant-mothers-improves-their-children-s-mental-health
#15
Jens Hainmueller, Duncan Lawrence, Linna Martén, Bernard Black, Lucila Figueroa, Michael Hotard, Tomás R Jiménez, Fernando Mendoza, Maria I Rodriguez, Jonas J Swartz, David D Laitin
The United States is embroiled in a debate about whether to protect or deport its estimated 11 million unauthorized immigrants, but the fact that these immigrants are also parents to more than 4 million U.S.-born children is often overlooked. We provide causal evidence of the impact of parents' unauthorized immigration status on the health of their U.S. citizen children. The Deferred Action for Childhood Arrivals (DACA) program granted temporary protection from deportation to more than 780,000 unauthorized immigrants...
August 31, 2017: Science
https://www.readbyqxmd.com/read/28839008/high-dislocation-density-induced-large-ductility-in-deformed-and-partitioned-steels
#16
B B He, B Hu, H W Yen, G J Cheng, Z K Wang, H W Luo, M X Huang
A wide variety of industrial applications require materials with high strength and ductility. Unfortunately, the strategies for increasing material strength, such as processing to create line defects (dislocations), tend to decrease ductility. We developed a strategy to circumvent this in inexpensive, medium Mn steel. Cold rolling followed by low-temperature tempering developed steel with metastable austenite grains embedded in a highly dislocated martensite matrix. This deformed and partitioned (D&P) process produced dislocation hardening, but retained high ductility both through the glide of intensive mobile dislocations and by allowing us to control martensitic transformation...
August 24, 2017: Science
https://www.readbyqxmd.com/read/28818973/mutations-in-the-promoter-of-the-telomerase-gene-tert-contribute-to-tumorigenesis-by-a-two-step-mechanism
#17
Kunitoshi Chiba, Franziska K Lorbeer, A Hunter Shain, David T McSwiggen, Eva Schruf, Areum Oh, Jekwan Ryu, Xavier Darzacq, Boris C Bastian, Dirk Hockemeyer
TERT promoter mutations (TPMs) are the most common non-coding mutations in cancer. The timing and consequences of TPMs have not been fully established. Here we show that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance. In vitro experiments revealed that TPMs do not prevent telomere attrition, resulting in cells with critically short and unprotected telomeres. Immortalization by TPMs requires a gradual upregulation of telomerase, coinciding with telomere fusions...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818971/dynamic-multinuclear-sites-formed-by-mobilized-copper-ions-in-no-x-selective-catalytic-reduction
#18
Christopher Paolucci, Ishant Khurana, Atish A Parekh, Sichi Li, Arthur J Shih, Hui Li, John R Di Iorio, Jonatan D Albarracin-Caballero, Aleksey Yezerets, Jeffrey T Miller, W Nicholas Delgass, Fabio H Ribeiro, William F Schneider, Rajamani Gounder
Copper ions exchanged into zeolites are active for the selective catalytic reduction (SCR) of NO x with NH3, but the low-temperature rate dependence on Cu volumetric density is inconsistent with reaction at single sites. We combine steady-state and transient kinetic measurements, x-ray absorption spectroscopy, and first-principles calculations to demonstrate that under reaction conditions, mobilized Cu ions can travel through zeolite windows and form transient ion pairs that participate in an O2-mediated Cu(I) → Cu(II) redox step integral to SCR...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818970/dna-replication-coupled-histone-modification-maintains-polycomb-gene-silencing-in-plants
#19
Danhua Jiang, Frédéric Berger
Propagation of patterns of gene expression through the cell cycle requires prompt restoration of epigenetic marks after the twofold dilution caused by DNA replication. Here, we show that the transcriptional repressive mark histone H3 lysine 27 trimethylation (H3K27me3) is restored in replicating plant cells through DNA replication-coupled modification of histone variant H3.1. Plants evolved a mechanism for efficient K27 trimethylation on H3.1, which is essential for inheritance of the silencing memory from mother to daughter cells...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818969/distinct-phases-of-polycomb-silencing-to-hold-epigenetic-memory-of-cold-in-arabidopsis
#20
Hongchun Yang, Scott Berry, Tjelvar S G Olsson, Matthew Hartley, Martin Howard, Caroline Dean
Gene silencing by Polycomb complexes is central to eukaryotic development. Cold-induced epigenetic repression of FLOWERING LOCUS C (FLC) in the plant Arabidopsis provides an opportunity to study initiation and maintenance of Polycomb silencing. Here, we show that a subset of Polycomb Repressive Complex 2 factors nucleate silencing in a small region within FLC, locally increasing H3K27me3 levels. This nucleation confers a silenced state that is metastably inherited, with memory held in the local chromatin. Metastable memory is then converted to stable epigenetic silencing through separate Polycomb factors, which spread across the locus after cold to enlarge the domain containing H3K27me3...
August 17, 2017: Science
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