506 research outputs found
Structural basis of the pleiotropic and specific phenotypic consequences of missense mutations in the multifunctional NAD(P)H:quinone oxidoreductase 1 and their pharmacological rescue
The multifunctional nature of human flavoproteins is critically linked to their ability to populate multiple conformational states. Ligand binding, post-translational modifications and disease-associated mutations can reshape this functional landscape, although the structure-function relationships of these effects are not well understood. Herein, we characterized the structural and functional consequences of two mutations (the cancer-associated P187S and the phosphomimetic S82D) on different ligation states which are relevant to flavin binding, intracellular stability and catalysis of the disease-associated NQO1 flavoprotein. We found that these mutations affected the stability locally and their effects propagated differently through the protein structure depending both on the nature of the mutation and the ligand bound, showing directional preference from the mutated site and leading to specific phenotypic manifestations in different functional traits (FAD binding, catalysis and inhibition, intracellular stability and pharmacological response to ligands). Our study thus supports that pleitropic effects of disease-causing mutations and phosphorylation events on human flavoproteins may be caused by long-range structural propagation of stability effects to different functional sites that depend on the ligation-state and site-specific perturbations. Our approach can be of general application to investigate these pleiotropic effects at the flavoproteome scale in the absence of high-resolution structural models. Š 202
Deformations of quantum field theories on spacetimes with Killing vector fields
The recent construction and analysis of deformations of quantum field
theories by warped convolutions is extended to a class of curved spacetimes.
These spacetimes carry a family of wedge-like regions which share the essential
causal properties of the Poincare transforms of the Rindler wedge in Minkowski
space. In the setting of deformed quantum field theories, they play the role of
typical localization regions of quantum fields and observables. As a concrete
example of such a procedure, the deformation of the free Dirac field is
studied.Comment: 35 pages, 3 figure
Manipulating the Tomonaga-Luttinger exponent by electric field modulation
We establish a theoretical framework for artificial control of the power-law
singularities in Tomonaga-Luttinger liquid states. The exponent governing the
power-law behaviors is found to increase significantly with an increase in the
amplitude of the periodic electric field modulation applied externally to the
system. This field-induced shift in the exponent indicates the tunability of
the transport properties of quasi-one-dimensional electron systems.Comment: 7 pages, 3 figure
Angle-resolved photoemission study of USb2: the 5f band structure
Single crystal antiferromagnetic USb2 was studied at 15K by angle-resolved
photoemission with an overall energy resolution of 24 meV. The measurements
unambiguously show the dispersion of extremely narrow bands situated near the
Fermi level. The peak at the Fermi level represents the narrowest feature
observed in 5f-electron photoemission to date. The natural linewidth of the
feature just below the Fermi level is not greater than 10 meV. Normal emission
data indicate a three dimensional aspect to the electronic structure of this
layered material.Comment: 22 pages including figure
A structural model for K2P potassium channels based on 23 pairs of interacting sites and continuum electrostatics
K2PĂ, the two-pore domain potassium background channel that determines cardiac rhythm in Drosophila melanogaster, and its homologues that establish excitable membrane activity in mammals are of unknown structure. K2P subunits have two pore domains flanked by transmembrane (TM) spans: TM1-P1-TM2-TM3-P2-TM4. To establish spatial relationships in K2PĂ, we identified pairs of sites that display electrostatic compensation. Channels silenced by the addition of a charge in pore loop 1 (P1) or P2 were restored to function by countercharges at specific second sites. A three-dimensional homology model was determined using the crystal structure of KV1.2, effects of K2PĂ mutations to establish alignment, and compensatory chargeâcharge pairs. The model was refined and validated by continuum electrostatic free energy calculations and covalent linkage of introduced cysteines. K2P channels use two subunits arranged so that the P1 and P2 loops contribute to one pore, identical P loops face each other diagonally across the pore, and the channel complex has bilateral symmetry with a fourfold symmetric selectivity filter
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Brazilian Flora 2020: Leveraging the power of a collaborative scientific network
The shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiver sity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxo nomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the worldâs known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that
used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals.
This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the worldâs most biodiverse countries. We further identify collection gaps and summarize future goals that extend be yond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still un equally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the coun try. In times of âscientific reductionismâ, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora.Fil: Gomes da Silva, Janaina. Jardim Botânico do Rio de Janeiro: Rio de Janeiro, BrasilFil: Filardi, Fabiana L.R. Jardim Botânico do Rio de Janeiro; BrasilFil: Barbosa, MarĂa Regina de V. Universidade Federal da ParaĂba: Joao Pessoa; BrasilFil: Baumgratz, JosĂŠ Fernando Andrade. Jardim Botânico do Rio de Janeiro; BrasilFil: de Mattos Bicudo, Carlos Eduardo. Instituto de Botânica. NĂşcleo de Pesquisa em Ecologia; BrasilFil: Cavalcanti, Taciana. Empresa Brasileira de Pesquisa AgropecuĂĄria Recursos GenĂŠticos e Biotecnologia; BrasilFil: Coelho, Marcus. Prefeitura Municipal de Campinas; BrasilFil: Ferreira da Costa, Andrea. Federal University of Rio de Janeiro. Museu Nacional. Department of Botany; BrasilFil: Costa, Denise. Instituto de Pesquisas Jardim Botanico do Rio de Janeiro; BrasilFil: Dalcin, Eduardo C. Rio de Janeiro Botanical Garden Research Institute; BrasilFil: Labiak, Paulo. Universidade Federal do Parana; BrasilFil: Cavalcante de Lima, Haroldo. Jardim Botânico do Rio de Janeiro; BrasilFil: Lohmann, Lucia. Universidade de SĂŁo Paulo; BrasilFil: Maia, Leonor. Universidade Federal de Pernambuco; BrasilFil: Mansano, Vidal de Freitas. Instituto de Pesquisas Jardim Botânico do Rio de Janeiro; Brasil. Jardim Botânico do Rio de Janeiro; BrasilFil: Menezes, Mariângela. Federal University of Rio de Janeiro. Museu Nacional. Department of Botany; BrasilFil: Morim, Marli. Instituto de Pesquisas Jardim Botânico do Rio de Janeiro; BrasilFil: Moura, Carlos Wallace do Nascimento. Universidade Estadual de Feira de Santana. Department of Biological Science; BrasilFil: Lughadha, Eimear NIck. Royal Botanic Gardens; Reino UnidoFil: Peralta, Denilson. Instituto de Pesquisas Ambientais; BrazilFil: Prado, Jefferson. Instituto de Pesquisas Ambientais; BrasilFil: Roque, NĂĄdia. Universidade Federal da Bahia; BrasilFil: Stehmann, Joao. Universidade Federal de Minas Gerais; BrasilFil: da Silva Sylvestre, Lana. Universidade Federal do Rio de Janeiro; BrasilFil: Trierveiler-Pereira, Larissa. Universidade Estadual de MaringĂĄ. Departamento de AnĂĄlises ClĂnicas e Biomedicina; BrasilFil: Walter, Bruno Machado Teles. EMBRAPA Cenargen BrasĂlia; BrasilFil: ZimbrĂŁo, Geraldo. Universidade Federal do Rio de Janeiro; BrasilFil: Forzza, Rafaela C. Jardim Botânico do Rio de Janeiro; BrasilFil: Morales, MatĂas. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de Recursos BiolĂłgicos; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas; Argentina. Universidad de MorĂłn. Facultad de AgronomĂa y Ciencias Agroalimentarias; Argentin
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