ALBERT

Description: Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase Pc Cel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium . Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the "Newton’s cradle"–like proton relay pathway of the catalytic cycle. Amide–imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions.

Description: A requirement for advancing antibody-based medicine is the development of proteins that can bind with high affinity to a specific epitope related to a critical protein activity site. As a part of generating such proteins, we have succeeded in creating a binding protein without changing epitope by complementarity-determining region 3 (CDR3) grafting (Inoue et al. , Affinity transfer to a human protein by CDR3 grafting of camelid VHH. Protein Sci. 20, 1971–1981). However, the affinity of the target-binding protein was low. In this manuscript, the affinity maturation of a target-binding protein was examined using CDR3-grafted camelid single domain antibody (VHH) as a model protein. Several amino acids in the CDR1 and CDR2 regions of VHH were mutated to tyrosines and/or serines and screened for affinity-matured proteins by using in silico analysis. The mutation of two amino acids in the CDR2 region to arginine and/or aspartic acid increased the affinity by decreasing the dissociation rate. The affinity of designed mutant increased by ~20-fold over that of the original protein. In the present study, candidate mutants were narrowed down using in silico screening and computational modelling, thus avoiding much in vitro analytical effort. Therefore, the method used in this study is expected to be one of the useful for promoting affinity maturation of antibodies.

Description: Positronium (Ps) is an ideal system for precision test of bound state quantum electrodynamics. The hyperfine splitting (HFS) of the ground state of Ps, which is one of the most precisely tested quantity, has a large discrepancy of 16 ppm (4.5 σ ) between previous experiments and theoretical calculation up to O ( α 3 ln α −1 ) and part of O ( α 3 ) corrections. A new experiment which reduces possible systematic uncertainties of Ps thermalization effect and nonuniformity of magnetic field was performed. It revealed that the Ps thermalization effect was as large as 10 ± 2 ppm. Treating the thermalization effect correctly, a new result of 203.3942 ± 0.0016(stat., 8.0 ppm) ± 0.0013(sys., 6.4 ppm) GHz was obtained. This result is consistent with theory within 1.1 σ , whereas it disfavors the previous experimental result by 2.6 σ . It shows that the Ps thermalization effect is crucial for precision measurement of HFS. Future prospects for improved precision are briefly discussed.

Description: Nostoc punctiforme is a versatile cyanobacterium that can live either independently or in symbiosis with plants from distinct taxa. Chemical cues from plants and N. punctiforme were shown to stimulate or repress, respectively, the differentiation of infectious motile filaments known as hormogonia. We have used a polyketide synthase mutant that...

Description: In fission yeast, the RNAi pathway is required for centromeric heterochromatin assembly. siRNAs derived from centromeric transcripts are incorporated into the RNA-induced transcriptional silencing (RITS) complex and direct it to nascent homologous transcripts. The RNA-induced transcriptional silencing-bound nascent transcripts further recruit the RNA-directed RNA polymerase complex (RDRC) to promote dsRNA synthesis and siRNA production. Heterochromatin coated with Swi6/Heterochromain Protein 1 is then formed following recruitment of chromatin modification machinery. Swi6 is also required for the upstream production of siRNA, although the mechanism for this has remained obscure. Here, we demonstrate that Swi6 recruits RDRC to heterochromatin through Ers1, an RNAi factor intermediate. An ers1+ mutant allele (ers1-C62) was identified in a genetic screen for mutants that alleviate centromeric silencing, and this phenotype was suppressed by overexpression of either the Hrr1 RDRC subunit or Clr4 histone H3-K9 methyltransferase. Ers1 physically interacts with Hrr1, and loss of Ers1 impairs RDRC centromeric localization. Although Ers1 failed to bind Clr4, a direct interaction with Swi6 was detected, and centromeric localization of Swi6 was enhanced by Clr4 overexpression in ers1-C62 cells. Consistent with this, deletion of swi6+ reduced centromeric localization of Ers1 and RDRC. Moreover, tethering of Ers1 or Hrr1 to centromeric heterochromatin partially bypassed Swi6 function. These findings demonstrate an alternative mechanism for RDRC recruitment and explain the essential role of Swi6/Heterochromain Protein 1 in RNAi-directed heterochromatin assembly.

Description: Mammalian RNAi machinery facilitating transcriptional gene silencing (TGS) is the RNA-induced transcriptional gene silencing-like (RITS-like) complex, comprising of Argonaute (Ago) and small interfering RNA (siRNA) components. We have previously demonstrated promoter-targeted siRNA induce TGS in human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV), which profoundly suppresses retrovirus replication via heterochromatin formation and histone methylation. Here, we examine subcellular co-localization of Ago proteins with promoter-targeted siRNAs during TGS of SIV and HIV-1 infection. Analysis of retrovirus-infected cells revealed Ago1 co-localized with siRNA in the nucleus, while Ago2 co-localized with siRNA in the inner nuclear envelope. Mismatched and scrambled siRNAs were observed in the cytoplasm, indicating sequence specificity. This is the first report directly visualizing nuclear compartment distribution of Ago-associated siRNA and further reveals a novel nuclear trafficking mechanism for RITS-like components involving the actin cytoskeleton. These results establish a model for elucidating mammalian TGS and suggest a fundamental mechanism underlying nuclear delivery of RITS-like components.

Description: Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| 〈 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahmadi, M -- Baquero-Ruiz, M -- Bertsche, W -- Butler, E -- Capra, A -- Carruth, C -- Cesar, C L -- Charlton, M -- Charman, A E -- Eriksson, S -- Evans, L T -- Evetts, N -- Fajans, J -- Friesen, T -- Fujiwara, M C -- Gill, D R -- Gutierrez, A -- Hangst, J S -- Hardy, W N -- Hayden, M E -- Isaac, C A -- Ishida, A -- Jones, S A -- Jonsell, S -- Kurchaninov, L -- Madsen, N -- Maxwell, D -- McKenna, J T K -- Menary, S -- Michan, J M -- Momose, T -- Munich, J J -- Nolan, P -- Olchanski, K -- Olin, A -- Povilus, A -- Pusa, P -- Rasmussen, C O -- Robicheaux, F -- Sacramento, R L -- Sameed, M -- Sarid, E -- Silveira, D M -- So, C -- Tharp, T D -- Thompson, R I -- van der Werf, D P -- Wurtele, J S -- Zhmoginov, A I -- England -- Nature. 2016 Jan 21;529(7586):373-6. doi: 10.1038/nature16491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Liverpool, Liverpool L697ZE, UK. ; Department of Physics, University of California at Berkeley, Berkeley, California 94720-7300, USA. ; Centre de Recherches en Physique des Plasmas (CRPP), Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. ; School of Physics and Astronomy, University of Manchester, Manchester M13 9PL, UK. ; Cockcroft Institute, Sci-Tech Daresbury, Warrington WA4 4AD, UK. ; Centre for Cold Matter, Blackett Laboratory, Imperial College London, Prince Consort Road, London SW7 2AZ, UK. ; Physics Department, European Organisation for Nuclear Research (CERN), CH-1211 Geneva 23, Switzerland. ; Department of Physics and Astronomy, York University, Toronto, Ontario M3J 1P3, Canada. ; Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-972, Brazil. ; Department of Physics, Swansea University, Swansea SA2 8PP, UK. ; Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark. ; TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia V6T 2A3, Canada. ; Department of Physics, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. ; Department of Physics, Stockholm University, SE-10691, Stockholm, Sweden. ; Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada. ; Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia V8P 5C2, Canada. ; Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana 47907, USA. ; Soreq Nuclear Research Center, Yavne, 81800, Israel. ; Department of Physics and Astronomy, University of Calgary, Calgary, Alberta T2N 1N4, Canada. ; ATAP, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26791725" target="_blank"〉PubMed〈/a〉

Description: Observation of the 1S–2S transition in trapped antihydrogen Nature 541, 7638 (2017). doi:10.1038/nature21040 Authors: M. Ahmadi, B. X. R. Alves, C. J. Baker, W. Bertsche, E. Butler, A. Capra, C. Carruth, C. L. Cesar, M. Charlton, S. Cohen, R. Collister, S. Eriksson, A. Evans, N. Evetts, J. Fajans, T. Friesen, M. C. Fujiwara, D. R. Gill, A. Gutierrez, J. S. Hangst, W. N. Hardy, M. E. Hayden, C. A. Isaac, A. Ishida, M. A. Johnson, S. A. Jones, S. Jonsell, L. Kurchaninov, N. Madsen, M. Mathers, D. Maxwell, J. T. K. McKenna, S. Menary, J. M. Michan, T. Momose, J. J. Munich, P. Nolan, K. Olchanski, A. Olin, P. Pusa, C. Ø. Rasmussen, F. Robicheaux, R. L. Sacramento, M. Sameed, E. Sarid, D. M. Silveira, S. Stracka, G. Stutter, C. So, T. D. Tharp, J. E. Thompson, R. I. Thompson, D. P. van der Werf & J. S. Wurtele The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S–2S transition by Hänsch to a precision of a few parts in 1015. Recent technological advances have allowed us to focus on antihydrogen—the antimatter equivalent of hydrogen. The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today’s Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S–2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10−10.

Description: Mesosiderites are unique stony-iron meteorites, composed of eucrite-like silicates and Fe–Ni metals. Their formation, including silicate–metal mixing and metamorphisms, provide important insights into early planetary processes in the inner solar system. This report describes the first in-situ U–Pb and Hf–W dating of zircon in a mesosiderite Asuka 882023. The U–Pb (4502 ± 75 Ma) and Hf–W (4532.8 + 5.7/-10.5 Ma) ages may represent timing of the zircon formation, which is considerably younger than crustal differentiation of the parent body. This evidence, combined with earlier studies of chronology, implies that mesosiderites were reheated at 4530–4520 Ma, clearly after the silicate–metal mixing.

Description: We report the first analytical expression purely constructed by a machine to determine photometric redshifts ( z phot ) of galaxies. A simple and reliable functional form is derived using 41 214 galaxies from the Sloan Digital Sky Survey Data Release 10 (SDSS-DR10) spectroscopic sample. The method automatically dropped the u and z bands, relying only on g , r and i for the final solution. Applying this expression to other 1417 181 SDSS-DR10 galaxies, with measured spectroscopic redshifts ( z spec ), we achieved a mean 〈( z phot – z spec )/(1 + z spec )〉 0.0086 and a scatter ( z phot – z spec )/(1 + z spec ) 0.045 when averaged up to z 1.0. The method was also applied to the PHAT0 data set, confirming the competitiveness of our results when faced with other methods from the literature. This is the first use of symbolic regression in cosmology, representing a leap forward in astronomy-data-mining connection.