1,467 research outputs found
Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core
The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 Å. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein–ligand interactions
Recommended from our members
Experimental study of laboratory-heated CM2 chondrites Mighei and Murchison
We conducted experimental heating of two CM2 chondrites, Murchison and Mighei, to study changes in their oxygen isotopic compositions and mineralogy and explore possible genetic relationships between MCCs and normal CMs
A Review of Trimen’s False Tiger Moth, Agoma trimenii (Lepidoptera: Agaristidae): Seasonal Biology, Potential Monitoring and Control Techniques
Trimen’s false tiger moth, Agoma trimenii (Lepidoptera: Agaristidae), has recently been found to occur in vineyards in the Northern Cape and Limpopo (Groblersdal area) provinces of South Africa. As little is known about the biology and behaviour of the moth, no official monitoring methods or economic thresholds relating to it, exist. Consequently, management and registered control options still require development. The first aim in the current review, was to gather and critically discuss all the available information on A. trimenii in the context of the information gained from field observations conducted in the Northern Cape, South Africa, during the 2016/2017 and 2017/2018 seasons. The paper also includes reporting on field observations made with regard to various aspects of the seasonal life cycle and ecology of A. trimenii, with a view to investigate, in future research, the potential biological control options available. Potential monitoring strategies of A. trimenii in the field were investigated. Various life stages of A. trimenii were identified, peak flight times were established, overlapping generations were determined, and the behavioural traits of all life stages were documented. Ultraviolet blue light traps proved to be the most promising potential monitoring strategy, with the prospect for an A. trimenii pheromone lure holding potential as an alternative monitoring strategy in future. With summarising all current information on A. trimenii, recommendations for growers to monitor and control A. trimenii are presented, towards the development of an integrated pest management system for the moth
Stepped vitrification technique for human ovarian tissue cryopreservation
The advantage of stepped vitrification (SV) is avoiding ice crystal nucleation, while decreasing the toxic effects of high cryoprotectant concentrations. We aimed to test this method for human ovarian tissue cryopreservation. Ovarian cortex was taken from 7 fertile adult women. Samples were subjected to an SV protocol performed in an automatic freezer, which allowed sample transfer to ever higher concentrations of dimethyl sulfoxide (DMSO) as the temperature was reduced. Histological evaluation of the vitrified-warmed tissue showed large numbers of degenerated follicles after 24 hours of in vitro culture. We therefore evaluated DMSO perfusion rates by X-ray computed tomography, ice crystal formation by freeze-substitution, and cell toxicity by transmission electron microscopy, seeking possible reasons why follicles degenerated. Although cryoprotectant perfusion was considered normal and no ice crystals were formed in the tissue, ultrastructural analysis detected typical signs of DMSO toxicity, such as mitochondria degeneration, alterations in chromatin condensation, cell vacuolization and extracellular matrix swelling in both stromal and follicular cells. The findings indicated that the method failed to preserve follicles due to the high concentrations of DMSO used. However, adaptations can be made to avoid toxicity to follicles caused by elevated levels of cryoprotectants.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2016/22947-
Super black hole as spinning particle: Supersymmetric baglike core
We consider particlelike solutions to supergravity based on the Kerr-Newman
black hole (BH) solution. The BH singularity is regularized by means of a phase
transition to a new vacuum state near the core region confining a dual gauge
field. Supersymmetric BPS-saturated domain wall model is suggested which can
provide this phase transition and formation the stable charged superconducting
core. For spinning particle the core takes the form of thin, relativistically
rotaiting disk.Comment: 9 pages, Latex, plenary talks given at the School-Workshop
Praha-Spin-2001 (Prague,July 15-28,2001) and at the XXIV International
Workshop on Fundamental Problems of HEP and Field Theory (IHEP, June 2001,
Protvino
Interacting dark matter contribution to the Galactic 511 keV gamma ray emission: constraining the morphology with INTEGRAL/SPI observations
We compare the full-sky morphology of the 511 keV gamma ray excess measured
by the INTEGRAL/SPI experiment to predictions of models based on dark matter
(DM) scatterings that produce low-energy positrons: either MeV-scale DM that
annihilates directly into e+e- pairs, or heavy DM that inelastically scatters
into an excited state (XDM) followed by decay into e+e- and the ground state.By
direct comparison to the data, we find that such explanations are consistent
with dark matter halo profiles predicted by numerical many-body simulations for
a Milky Way-like galaxy. Our results favor an Einasto profile over the cuspier
NFW distribution and exclude decaying dark matter scenarios whose predicted
spatial distribution is too broad. We obtain a good fit to the shape of the
signal using six fewer degrees of freedom than previous empirical fits to the
511 keV data. We find that the ratio of flux at Earth from the galactic bulge
to that of the disk is between 1.9 and 2.4, taking into account that 73% of the
disk contribution may be attributed to the beta decay of radioactive 26Al.Comment: 7 pages, 4 figures. Includes minor corrections, and a discussion of
threshold energies in XDM models. Published in JCA
Thermodynamics of non-local materials: extra fluxes and internal powers
The most usual formulation of the Laws of Thermodynamics turns out to be
suitable for local or simple materials, while for non-local systems there are
two different ways: either modify this usual formulation by introducing
suitable extra fluxes or express the Laws of Thermodynamics in terms of
internal powers directly, as we propose in this paper. The first choice is
subject to the criticism that the vector fluxes must be introduced a posteriori
in order to obtain the compatibility with the Laws of Thermodynamics. On the
contrary, the formulation in terms of internal powers is more general, because
it is a priori defined on the basis of the constitutive equations. Besides it
allows to highlight, without ambiguity, the contribution of the internal powers
in the variation of the thermodynamic potentials. Finally, in this paper, we
consider some examples of non-local materials and derive the proper expressions
of their internal powers from the power balance laws.Comment: 16 pages, in press on Continuum Mechanics and Thermodynamic
Revisiting consistency conditions for quantum states of systems on closed timelike curves: an epistemic perspective
There has been considerable recent interest in the consequences of closed
timelike curves (CTCs) for the dynamics of quantum mechanical systems. A vast
majority of research into this area makes use of the dynamical equations
developed by Deutsch, which were developed from a consistency condition that
assumes that mixed quantum states uniquely describe the physical state of a
system. We criticise this choice of consistency condition from an epistemic
perspective, i.e., a perspective in which the quantum state represents a state
of knowledge about a system. We demonstrate that directly applying Deutsch's
condition when mixed states are treated as representing an observer's knowledge
of a system can conceal time travel paradoxes from the observer, rather than
resolving them. To shed further light on the appropriate dynamics for quantum
systems traversing CTCs, we make use of a toy epistemic theory with a strictly
classical ontology due to Spekkens and show that, in contrast to the results of
Deutsch, many of the traditional paradoxical effects of time travel are
present.Comment: 10 pages, 6 figures, comments welcome; v2 added references and
clarified some points; v3 published versio
Classical and Quantum Strings in compactified pp-waves and Godel type Universes
We consider Neveu-Schwarz pp-waves with spacetime supersymmetry. Upon
compactification of a spacelike direction, these backgrounds develop Closed
Null Curves (CNCs) and Closed Timelike Curves (CTCs), and are U-dual to
supersymmetric Godel type universes. We study classical and quantum strings in
this background, with emphasis on the strings winding around the compact
direction. We consider two types of strings: long strings stabilized by NS flux
and rotating strings which are stabilized against collapse by angular momentum.
Some of the latter strings wrap around CNCs and CTCs, and are thus a potential
source of pathology. We analyze the partition function, and in particular
discuss the effects of these string states. Although our results are not
conclusive, the partition function seems to be dramatically altered due to the
presence of CNCs and CTCs. We discuss some interpretations of our results,
including a possible sign of unitary violation.Comment: 42 pages, LaTeX, 2 figure
The implications of service quality gaps for strategy implementation
This article addresses the problem of service quality strategy implementation and
proposes three interrelated models: a static model of the organisation; a comprehensive
dynamic model of the implementation process, both synthesised from the literature; and
a mixed model, which integrates static and dynamic models. The mixed model is
combined with the service quality gaps (SQGs) model, drawn at a previous congress
paper, to propose a map of the pattern of SQGs occurring at each implementation stage;
the organisational variables that can be manipulated to eliminate SQGs; and several
implications to practising managers
- …