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https://www.readbyqxmd.com/read/28729352/optical-imaging-of-surface-chemistry-and-dynamics-in-confinement
#1
Carlos Macias-Romero, Igor Nahalka, Halil I Okur, Sylvie Roke
We imaged the interfacial structure and dynamics of water in a microscopically confined geometry in three dimensions and on millisecond time scales with a 3D structurally illuminated wide-field second harmonic microscope. Image contrast reports on the orientational order of interfacial water, induced by charge-dipole interactions between water molecules and surface charges. The images were converted into surface potential maps. Spatially resolved surface acid dissociation constant pKa,s values were determined for the silica deprotonation reaction by following pH induced chemical changes on the curved and confined surfaces of a glass micro-capillary immersed in aqueous solutions...
July 20, 2017: Science
https://www.readbyqxmd.com/read/28729351/we-still-need-to-beat-hiv
#2
EDITORIAL
François Dabis, Linda-Gail Bekker
No abstract text is available yet for this article.
July 20, 2017: Science
https://www.readbyqxmd.com/read/28729350/structures-of-the-crispr-genome-integration-complex
#3
Addison V Wright, Jun-Jie Liu, Gavin J Knott, Kevin W Doxzen, Eva Nogales, Jennifer A Doudna
CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo-electron microscopy structure of the full CRISPR locus integration complex including the accessory protein Integration Host Factor (IHF). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences...
July 20, 2017: Science
https://www.readbyqxmd.com/read/28705990/systemic-pan-ampk-activator-mk-8722-improves-glucose-homeostasis-but-induces-cardiac-hypertrophy
#4
Robert W Myers, Hong-Ping Guan, Juliann Ehrhart, Aleksandr Petrov, Srinivasa Prahalada, Effie Tozzo, Xiaodong Yang, Marc M Kurtz, Maria Trujillo, Dinko Gonzalez Trotter, Danqing Feng, Shiyao Xu, George Eiermann, Marie A Holahan, Daniel Rubins, Stacey Conarello, Xiaoda Niu, Sandra C Souza, Corin Miller, Jinqi Liu, Ku Lu, Wen Feng, Ying Li, Ronald E Painter, James A Milligan, Huaibing He, Franklin Liu, Aimie Ogawa, Douglas Wisniewski, Rory J Rohm, Liyang Wang, Michelle Bunzel, Ying Qian, Wei Zhu, Hongwu Wang, Bindu Bennet, Lisa LaFranco Scheuch, Guillermo E Fernandez, Cai Li, Michael Klimas, Gaochao Zhou, Margaret van Heek, Tesfaye Biftu, Ann Weber, David E Kelley, Nancy Thornberry, Mark D Erion, Daniel M Kemp, Iyassu K Sebhat
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite investigations over three decades, the biological roles of AMPK and its potential as a drug target remain incompletely understood, due largely to the lack of optimized pharmacological tools. We now report MK-8722, a potent, direct, allosteric activator of all twelve mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induces robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia...
July 13, 2017: Science
https://www.readbyqxmd.com/read/28705989/emergent-cellular-self-organization-and-mechanosensation-initiate-follicle-pattern-in-the-avian-skin
#5
Amy E Shyer, Alan R Rodrigues, Grant G Schroeder, Elena Kassianidou, Sanjay Kumar, Richard M Harland
The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling...
July 13, 2017: Science
https://www.readbyqxmd.com/read/28705988/large-amplitude-transfer-motion-of-hydrated-excess-protons-mapped-by-ultrafast-2d-ir-spectroscopy
#6
Fabian Dahms, Benjamin P Fingerhut, Erik T J Nibbering, Ehud Pines, Thomas Elsaesser
Solvation and transport of excess protons in aqueous systems play a fundamental role in acid-base chemistry and biochemical processes. Here, we map ultrafast proton excursions along the proton transfer coordinate by 2D infrared (IR) spectroscopy, both in bulk water and in a Zundel cation (H5O2)(+) motif selectively prepared in acetonitrile. Electric fields from the environment and stochastic hydrogen bond motions induce fluctuations of the proton double-minimum potential. Within the lifetime of a particular hydration geometry, the proton explores a multitude of positions on a sub-100 fs time scale...
July 13, 2017: Science
https://www.readbyqxmd.com/read/28705987/east-not-least-for-pacific-bluefin-tuna
#7
By Daniel J Madigan, Andre Boustany, Bruce B Collette
More Pacific bluefin migrate across the ocean than previously recognized.
July 13, 2017: Science
https://www.readbyqxmd.com/read/28663440/elabela-deficiency-promotes-preeclampsia-and-cardiovascular-malformations-in-mice
#8
Lena Ho, Marie Van Dijk, Sam Tan Jian Chye, Daniel M Messerschmidt, Serene C Chng, Sheena Ong, Ling Ka Yi, Souad Boussata, Grace Hui-Yi Goh, Gijs B Afink, Chin Yan Lim, N Ray Dunn, Davor Solter, Barbara B Knowles, Bruno Reversade
Pre-eclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. While PE is the leading cause of fetal and maternal morbidity/mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis...
June 29, 2017: Science
https://www.readbyqxmd.com/read/28663439/a-cyclic-oligonucleotide-signaling-pathway-in-type-iii-crispr-cas-systems
#9
Migle Kazlauskiene, Georgij Kostiuk, Česlovas Venclovas, Gintautas Tamulaitis, Virginijus Siksnys
Type III CRISPR-Cas systems in prokaryotes provide immunity against invading nucleic acids through the coordinated degradation of transcriptionally-active DNA and its transcripts by the Csm effector complex. Cas10 subunit of the complex contains a HD-nuclease domain responsible for DNA degradation and two Palm domains with elusive functions. In addition, Csm6, an RNase that is not part of the complex, is also required to provide full immunity. We show here that target RNA binding by the Csm effector complex of Streptococcus thermophilus triggers Cas10 to synthesize cyclic oligoadenylates cOAn (n = 2-6) via the Palm domains...
June 29, 2017: Science
https://www.readbyqxmd.com/read/28663438/bismuthene-on-a-sic-substrate-a-candidate-for-a-high-temperature-quantum-spin-hall-material
#10
F Reis, G Li, L Dudy, M Bauernfeind, S Glass, W Hanke, R Thomale, J Schäfer, R Claessen
Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents, but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high-Z element, and is experimentally realized as a bismuth honeycomb lattice on top of the insulator SiC(0001)...
June 29, 2017: Science
https://www.readbyqxmd.com/read/28642235/atomic-layered-au-clusters-on-%C3%AE-moc-as-catalysts-for-the-low-temperature-water-gas-shift-reaction
#11
Siyu Yao, Xiao Zhang, Wu Zhou, Rui Gao, Wenqian Xu, Yifan Ye, Lili Lin, Xiaodong Wen, Ping Liu, Bingbing Chen, Ethan Crumlin, Jinghua Guo, Zhijun Zuo, Weizhen Li, Jinglin Xie, Li Lu, Christopher J Kiely, Lin Gu, Chuan Shi, José A Rodriguez, Ding Ma
The water-gas shift (WGS) reaction (CO+H2O=H2+CO2) is an essential process for hydrogen generation and CO removal in various energy-related chemical operations. This equilibrium-limited reaction is favored at a low working temperature. Potential application in fuel cells also requires a WGS catalyst to be highly active, stable and energy-efficient and match the working temperature of on-site hydrogen generation and consumption units. We synthesized Au layered clusters on an α-MoC substrate to create an interfacial catalyst system for the ultra-low-temperature WGS reaction...
June 22, 2017: Science
https://www.readbyqxmd.com/read/28642234/reconfiguration-of-dna-molecular-arrays-driven-by-information-relay
#12
Jie Song, Zhe Li, Pengfei Wang, Travis Meyer, Chengde Mao, Yonggang Ke
Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes, such as intricate signaling cascades. One key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex behaviors in controllable systems. We demonstrated prescribed, long-range information relay in an artificial molecular array assembled from modular DNA structural units. The dynamic DNA molecular array exhibits transformations with programmable initiation, propagation, and regulation...
June 22, 2017: Science
https://www.readbyqxmd.com/read/28619717/photoinduced-decarboxylative-borylation-of-carboxylic-acids
#13
Alexander Fawcett, Johan Pradeilles, Yahui Wang, Tatsuya Mutsuga, Eddie L Myers, Varinder K Aggarwal
The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. Here we report that this transformation can be effected by illuminating the N-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent, bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process...
June 15, 2017: Science
https://www.readbyqxmd.com/read/28619716/ratchet-like-polypeptide-translocation-mechanism-of-the-aaa-disaggregase-hsp104
#14
Stephanie N Gates, Adam L Yokom, JiaBei Lin, Meredith E Jackrel, Alexandrea N Rizo, Nathan M Kendsersky, Courtney E Buell, Elizabeth A Sweeny, Korrie L Mack, Edward Chuang, Mariana P Torrente, Min Su, James Shorter, Daniel R Southworth
Hsp100 polypeptide translocases are conserved AAA+ machines that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from S. cerevisiae solubilizes stress-induced amorphous aggregates and amyloid. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-EM structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80 Å-long unfolded polypeptide along the axial channel...
June 15, 2017: Science
https://www.readbyqxmd.com/read/28619715/liquefied-gas-electrolytes-for-electrochemical-energy-storage-devices
#15
Cyrus S Rustomji, Yangyuchen Yang, Tae Kyoung Kim, Jimmy Mac, Young Jin Kim, Elizabeth Caldwell, Hyeseung Chung, Y Shirley Meng
Electrochemical capacitors and Li-ion batteries have seen little change in their electrolyte chemistry since their commercialization which has limited improvements in device performance. Combining superior physical and chemical properties and a high dielectric-fluidity factor, the use of electrolytes based on solvent systems which exclusively use components which are typically gaseous under standard conditions show a wide potential window of stability and excellent performance over an extended temperature range...
June 15, 2017: Science
https://www.readbyqxmd.com/read/28596311/fatty-acids-in-arbuscular-mycorrhizal-fungi-are-synthesized-by-the-host-plant
#16
Leonie H Luginbuehl, Guillaume N Menard, Smita Kurup, Harrie Van Erp, Guru V Radhakrishnan, Andrew Breakspear, Giles E D Oldroyd, Peter J Eastmond
Plants form beneficial associations with arbuscular mycorrhizal fungi, which facilitate nutrient acquisition from the soil. In return, the fungi receive organic carbon from the plants. The transcription factor RAM1 (REQUIRED FOR ARBUSCULAR MYCORRHIZATION 1) is crucial for this symbiosis, and we demonstrate that it is required and sufficient for the induction of a lipid biosynthetic pathway that is expressed in plant cells accommodating fungal arbuscules. Lipids are transferred from the plant to mycorrhizal fungi, which are fatty acid auxotrophs, and this lipid export requires the glycerol-3-phosphate acyltransferase RAM2, a direct target of RAM1...
June 8, 2017: Science
https://www.readbyqxmd.com/read/28596310/pittsburgh-myth-paris-reality
#17
EDITORIAL
Patrick Gallagher
No abstract text is available yet for this article.
June 8, 2017: Science
https://www.readbyqxmd.com/read/28596308/mismatch-repair-deficiency-predicts-response-of-solid-tumors-to-pd-1-blockade
#18
Dung T Le, Jennifer N Durham, Kellie N Smith, Hao Wang, Bjarne R Bartlett, Laveet K Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S Luber, Fay Wong, Nilofer S Azad, Agnieszka A Rucki, Dan Laheru, Ross Donehower, Atif Zaheer, George A Fisher, Todd S Crocenzi, James J Lee, Tim F Greten, Austin G Duffy, Kristen K Ciombor, Aleksandra D Eyring, Bao H Lam, Andrew Joe, S Peter Kang, Matthias Holdhoff, Ludmila Danilova, Leslie Cope, Christian Meyer, Shibin Zhou, Richard M Goldberg, Deborah K Armstrong, Katherine M Bever, Amanda N Fader, Janis Taube, Franck Housseau, David Spetzler, Nianqing Xiao, Drew M Pardoll, Nickolas Papadopoulos, Kenneth W Kinzler, James R Eshleman, Bert Vogelstein, Robert A Anders, Luis A Diaz
The genomes of cancers deficient in mismatch repair (MMR) contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with MMR deficiency were sensitive to immune checkpoint blockade with anti-PD-1 antibodies. We have expanded this study to now evaluate efficacy of PD-1 blockade in patients with advanced MMR-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients and complete responses were achieved in 21% of patients...
June 8, 2017: Science
https://www.readbyqxmd.com/read/28596307/plants-transfer-lipids-to-sustain-colonization-by-mutualistic-mycorrhizal-and-parasitic-fungi
#19
Yina Jiang, Wanxiao Wang, Qiujin Xie, Na Liu, Lixia Liu, Dapeng Wang, Xiaowei Zhang, Chen Yang, Xiaoya Chen, Dingzhong Tang, Ertao Wang
Arbuscular mycorrhizal (AM) fungi facilitate plant uptake of mineral nutrients and draw organic nutrients from the plant. Organic nutrients are thought to be supplied primarily in the form of sugars. Here we show that the AM fungus Rhizophagus irregularis is a fatty acid auxotroph and that fatty acids synthesized in the host plants are transferred to the fungus to sustain mycorrhizal colonization. The transfer is dependent on RAM2 (REQUIRED FOR ARBUSCULAR MYCORRHIZATION 2) and the ATP binding cassette transporter-mediated plant lipid export pathway...
June 8, 2017: Science
https://www.readbyqxmd.com/read/28572455/mir-183-cluster-scales-mechanical-pain-sensitivity-by-regulating-basal-and-neuropathic-pain-genes
#20
Changgeng Peng, Lili Li, Ming-Dong Zhang, Carolina Bengtsson Gonzales, Marc Parisien, Inna Belfer, Dmitry Usoskin, Hind Abdo, Alessandro Furlan, Martin Häring, Francois Lallemend, Tibor Harkany, Luda Diatchenko, Tomas Hökfelt, Jens Hjerling-Leffler, Patrik Ernfors
Nociception is protective and prevents tissue damage but can also facilitate chronic pain. Whether a general principle governs these two types of pain is unknown. Here, we show that both basal mechanical and neuropathic pain are controlled by the microRNA-183 (miR-183) cluster in mice. This single cluster controls more than 80% of neuropathic pain-regulated genes and scales basal mechanical sensitivity and mechanical allodynia by regulating auxiliary voltage-gated calcium channel subunits α2δ-1 and α2δ-2...
June 16, 2017: Science
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