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https://www.readbyqxmd.com/read/28798047/mtor-regulates-metabolic-adaptation-of-apcs-in-the-lung-and-controls-the-outcome-of-allergic-inflammation
#1
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28798046/loss-of-a-mammalian-circular-rna-locus-causes-mirna-deregulation-and-affects-brain-function
#2
Monika Piwecka, Petar Glažar, Luis R Hernandez-Miranda, Sebastian Memczak, Susanne A Wolf, Agnieszka Rybak-Wolf, Andrei Filipchyk, Filippos Klironomos, Cledi Alicia Cerda Jara, Pascal Fenske, Thorsten Trimbuch, Vera Zywitza, Mireya Plass, Luisa Schreyer, Salah Ayoub, Christine Kocks, Ralf Kühn, Christian Rosenmund, Carmen Birchmeier, Nikolaus Rajewsky
Hundreds of circular RNAs (circRNAs) are highly abundant in mammalian brain, with oftentimes conserved expression. Here, we show that the circRNA Cdr1as is massively bound by miR-7 and miR-671 in the human and mouse brain. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating, a deficit in the ability to filter out unnecessary information associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28798045/global-mrna-polarization-regulates-translation-efficiency-in-the-intestinal-epithelium
#3
Andreas E Moor, Matan Golan, Efi E Massasa, Doron Lemze, Tomer Weizman, Rom Shenhav, Shaked Baydatch, Orel Mizrahi, Roni Winkler, Ofra Golani, Noam Stern-Ginossar, Shalev Itzkovitz
Asymmetric mRNA localization facilitates efficient translation in cells such as neurons and fibroblasts. However, the extent and significance of mRNA polarization in epithelial tissues are unclear. Here, we used single molecule transcript imaging and subcellular transcriptomics to uncover global apical-basal intracellular polarization of mRNA in the mouse intestinal epithelium. The localization of mRNAs did not generally overlap protein localization. Instead, ribosomes were more abundant on the apical sides, and apical transcripts were consequently more efficiently translated...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28798044/hydrogenation-of-fluoroarenes-direct-access-to-all-cis-multi-fluorinated-cycloalkanes
#4
Mario P Wiesenfeldt, Zackaria Nairoukh, Wei Li, Frank Glorius
All-cis-multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Only very few such motifs have been prepared, with their syntheses requiring multistep sequences from diastereoselectively prefunctionalized precursors. Herein, we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28798043/inactivation-of-porcine-endogenous-retrovirus-in-pigs-using-crispr-cas9
#5
Dong Niu, Hong-Jiang Wei, Lin Lin, Haydy George, Tao Wang, I-Hsiu Lee, Hong-Ye Zhao, Yong Wang, Yinan Kan, Ellen Shrock, Emal Lesha, Gang Wang, Yonglun Luo, Yubo Qing, Deling Jiao, Heng Zhao, Xiaoyang Zhou, Shouqi Wang, Hong Wei, Marc Güell, George M Church, Luhan Yang
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28775215/observation-of-coherent-elastic-neutrino-nucleus-scattering
#6
D Akimov, J B Albert, P An, C Awe, P S Barbeau, B Becker, V Belov, A Brown, A Bolozdynya, B Cabrera-Palmer, M Cervantes, J I Collar, R J Cooper, R L Cooper, C Cuesta, D J Dean, J A Detwiler, A Eberhardt, Y Efremenko, S R Elliott, E M Erkela, L Fabris, M Febbraro, N E Fields, W Fox, Z Fu, A Galindo-Uribarri, M P Green, M Hai, M R Heath, S Hedges, D Hornback, T W Hossbach, E B Iverson, L J Kaufman, S Ki, S R Klein, A Khromov, A Konovalov, M Kremer, A Kumpan, C Leadbetter, L Li, W Lu, K Mann, D M Markoff, K Miller, H Moreno, P E Mueller, J Newby, J L Orrell, C T Overman, D S Parno, S Penttila, G Perumpilly, H Ray, J Raybern, D Reyna, G C Rich, D Rimal, D Rudik, K Scholberg, B J Scholz, G Sinev, W M Snow, V Sosnovtsev, A Shakirov, S Suchyta, B Suh, R Tayloe, R T Thornton, I Tolstukhin, J Vanderwerp, R L Varner, C J Virtue, Z Wan, J Yoo, C-H Yu, A Zawada, J Zettlemoyer, A M Zderic
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28775214/organotypic-vasculature-from-descriptive-heterogeneity-to-functional-pathophysiology
#7
REVIEW
Hellmut G Augustin, Gou Young Koh
Blood vessels form one of the body's largest surfaces serving as critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism as well as cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (EC), whose cellular and molecular heterogeneity has long been recognized...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28775213/lactobacillus-reuteri-induces-gut-intraepithelial-cd4-cd8%C3%AE-%C3%AE-t-cells
#8
Luisa Cervantes-Barragan, Jiani N Chai, Ma Diarey Tianero, Blanda DiLuccia, Philip P Ahern, Joseph Merriman, Victor S Cortez, Michael G Caparon, Mohamed S Donia, Susan Gilfillan, Marina Cella, Jeffrey I Gordon, Chyi-Song Hsieh, Marco Colonna
The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28775212/identification-of-a-primordial-asteroid-family-constrains-the-original-planetesimal-population
#9
Marco Delbo', Kevin Walsh, Bryce Bolin, Chrysa Avdellidou, Alessandro Morbidelli
A quarter of known asteroids is associated with over a hundred distinct asteroid families, meaning that these asteroids originate as impact fragments from the family parent bodies. The determination of which asteroids of the remaining population are members of undiscovered families, or accreted as planetesimals from the protoplanetary disk, would constrain a critical phase of planetary formation by unveiling the unknown planetesimal size distribution. We discovered a 4 Gyr-old asteroid family extending across the entire inner part of the Main Belt, whose members include most dark asteroids previously unlinked to families...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28775211/structure-of-the-complete-elongation-complex-of-rna-polymerase-ii-with-basal-factors
#10
Haruhiko Ehara, Takeshi Yokoyama, Hideki Shigematsu, Shigeyuki Yokoyama, Mikako Shirouzu, Shun-Ichi Sekine
In the early stage of transcription, eukaryotic RNA polymerase II (Pol II) exchanges initiation factors with elongation factors to form an elongation complex (EC) for processive transcription. Here, we report the structure of the Pol II EC bound with the basal elongation factors Spt4/5, Elf1, and TFIIS. Spt4/5 (the Spt4/Spt5 complex) and Elf1 modify a wide area of the Pol II surface. Elf1 bridges the Pol II central cleft, completing the "DNA entry tunnel" for downstream DNA. Spt4 and the Spt5 NGN and KOW1 domains encircle the upstream DNA, constituting a "DNA exit tunnel"...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28775210/robust-epitaxial-growth-of-two-dimensional-heterostructures-multiheterostructures-and-superlattices
#11
Zhengwei Zhang, Peng Chen, Xidong Duan, Ketao Zang, Jun Luo, Xiangfeng Duan
We report a general synthetic strategy for highly robust growth of diverse heterostructures, multiheterostructures, and superlattices from two-dimensional (2D) atomic crystals. A reverse flow during the temperature swing stage in sequential vapor deposition growth process allowed us to cool the existing 2D crystals to prevent undesired thermal degradation and uncontrolled homogeneous nucleation, thus enabling highly robust block-by-block epitaxial growth. Raman and photoluminescence mapping studies showed that a wide range of 2D heterostructures (such as WS2-WSe2 and WS2-MoSe2), multiheterostructures (such as WS2-WSe2-MoS2 and WS2-MoSe2-WSe2), and superlattices (such as WS2-WSe2-WS2-WSe2-WS2) were readily prepared with precisely controlled spatial-modulation...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28751471/structure-of-a-symmetric-photosynthetic-reaction-center-photosystem
#12
Christopher Gisriel, Iosifina Sarrou, Bryan Ferlez, John H Golbeck, Kevin E Redding, Raimund Fromme
Reaction centers are pigment-protein complexes that drive photosynthesis by converting light into chemical energy. It is believed that they arose once from a homodimeric protein. The symmetry of a homodimer is broken in heterodimeric reaction center structures, such as those reported previously. The 2.2-Å resolution X-ray structure of the homodimeric reaction center/photosystem from the phototroph, Heliobacterium modesticaldum, exhibits perfect C2 symmetry. The core polypeptide dimer and two small subunits coordinate 54 (bacterio)chlorophylls and 2 carotenoids that capture and transfer energy to the electron transfer chain at the center, which performs charge separation and consists of 6 (bacterio)chlorophylls and an iron-sulfur cluster; unlike other reaction centers, it lacks a bound quinone...
July 27, 2017: Science
https://www.readbyqxmd.com/read/28751470/paneth-cells-secrete-lysozyme-via-secretory-autophagy-during-bacterial-infection-of-the-intestine
#13
Shai Bel, Mihir Pendse, Yuhao Wang, Yun Li, Kelly A Ruhn, Brian Hassell, Tess Leal, Sebastian E Winter, Ramnik J Xavier, Lora V Hooper
Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins including lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with secretion and compromising intestinal antimicrobial defense. Here we show that during bacterial infection, lysozyme is rerouted through secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination...
July 27, 2017: Science
https://www.readbyqxmd.com/read/28729352/optical-imaging-of-surface-chemistry-and-dynamics-in-confinement
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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/28663440/elabela-deficiency-promotes-preeclampsia-and-cardiovascular-malformations-in-mice
#20
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
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